Journal articles: 'NDM'

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Lin, Dawei, Moran Wang, Feifei Yu, Wenhui Shi, Fuli Luo, Chao Wu, Jingwen Yang, and Wenming Ma. "Identification and expression pattern of three sex-related genes in the shrimp Neocaridina denticulata sinensis (Decapoda, Caridea)." Crustaceana 95, no. 7 (September 23, 2022): 723–46. http://dx.doi.org/10.1163/15685403-bja10219.

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Abstract The sex determination and differentiation process of economically important crustaceans have been regarded as the focus of aquaculture for a long time, because of the sex-related weight differences. Neocaridina denticulata sinensis makes a suitable animal model for studying crustaceans because it can reproduce many times under artificial control and has a short reproductive cycle. Male and female sex characteristics of the adult rice shrimp Neocaridina d. sinensis are morphologically obvious, but not in embryos and juvenile stages. At present, sex-specific DNA markers have not yet been developed. To produce a reliable molecular marker for sex in Neocaridina and to investigate molecular sex differentiation, we therefore focused on identifying sex-specific transcriptomic differences. In this study, we found three sex-specific expression genes, NDM, Sushi, and NDF, after screening a large number of transcriptome data. NDM and Sushi are male-specific expression genes, and NDF is a female-specific expression gene. Semi-quantitative RT-PCR analysis showed that NDM and NDF can act as molecular markers for the sex identification of Neocaridina in different developmental stages, especially sex identification for embryos and juveniles with the same morphological characteristics. However, Sushi can only act as a molecular marker for the sex identification of Neocaridina in adult stages. Furthermore, in situ hybridization showed that a strong positive signal of NDM was detected in the male testis. At the same time, we explored the relationship between these three genes and sex differentiation. The results of RNA interference treatment show that knockdown of nd-IAG (Neocaridina denticulata sinensis insulin-like androgenic gland hormone) can change the expression of NDM and NDF. On the basis of the expression of the male-specific gene NDM and the female-specific gene NDF, we developed a molecular test that for the first time allows the unambiguous sex determination of Neocaridina samples lacking external sex-specific features from juvenile stages onward.

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Patel, Shilla. "NDM-1." Nursing 42, no. 4 (April 2012): 67–68. http://dx.doi.org/10.1097/01.nurse.0000412934.58501.8c.

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Ali, Abid, Divya Gupta, Gaurava Srivastava, Ashok sharma, and Asad U. Khan. "Molecular and computational approaches to understand resistance of New Delhi metallo β-lactamase variants (NDM-1, NDM-4, NDM-5, NDM-6, NDM-7)-producing strains against carbapenems." Journal of Biomolecular Structure and Dynamics 37, no. 8 (December 5, 2018): 2061–71. http://dx.doi.org/10.1080/07391102.2018.1475261.

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Boutal, Hervé, Thierry Naas, Karine Devilliers, Saoussen Oueslati, Laurent Dortet, Sandrine Bernabeu, Stéphanie Simon, and Hervé Volland. "Development and Validation of a Lateral Flow Immunoassay for Rapid Detection of NDM-Producing Enterobacteriaceae." Journal of Clinical Microbiology 55, no. 7 (April 12, 2017): 2018–29. http://dx.doi.org/10.1128/jcm.00248-17.

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ABSTRACT The global spread of carbapenemase-producing Enterobacteriaceae (CPE) that are often resistant to most, if not all, classes of antibiotics is a major public health concern. The NDM-1 carbapenemase is among the most worrisome carbapenemases given its rapid worldwide spread. We have developed and evaluated a lateral flow immunoassay (LFIA) (called the NDM LFIA) for the rapid and reliable detection of NDM-like carbapenemase-producing Enterobacteriaceae from culture colonies. We evaluated the NDM LFIA using 175 reference enterobacterial isolates with characterized β-lactamase gene content and 74 nonduplicate consecutive carbapenem-resistant clinical isolates referred for expertise to the French National Reference Center (NRC) for Antibiotic Resistance during a 1-week period (in June 2016). The reference collection included 55 non-carbapenemase producers and 120 carbapenemase producers, including 27 NDM producers. All 27 NDM-like carbapenemase producers of the reference collection were correctly detected in less than 15 min by the NDM LFIA, including 22 strains producing NDM-1, 2 producing NDM-4, 1 producing NDM-5, 1 producing NDM-7, and 1 producing NDM-9. All non-NDM-1 producers gave a negative result with the NDM LFIA. No cross-reaction was observed with carbapenemases (VIM, IMP, NDM, KPC, and OXA-48-like), extended-spectrum β-lactamases (ESBLs) (TEM, SHV, and CTX-M), AmpCs (CMY-2, DHA-2, and ACC-1), and oxacillinases (OXA-1, -2, -9, and -10). Similarly, among the 74 referred nonduplicate consecutive clinical isolates, all 7 NDM-like producers were identified. Overall, the sensitivity and specificity of the assay were 100% for NDM-like carbapenemase detection with strains cultured on agar. The NDM LFIA was efficient, rapid, and easy to implement in the routine workflow of a clinical microbiology laboratory for the confirmation of NDM-like carbapenemase-producing Enterobacteriaceae .

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Pérez-Vázquez, María, Pedro J. Sola Campoy, Adriana Ortega, Verónica Bautista, Sara Monzón, Guillermo Ruiz-Carrascoso, Jesus Mingorance, et al. "Emergence of NDM-producing Klebsiella pneumoniae and Escherichia coli in Spain: phylogeny, resistome, virulence and plasmids encoding blaNDM-like genes as determined by WGS." Journal of Antimicrobial Chemotherapy 74, no. 12 (September 3, 2019): 3489–96. http://dx.doi.org/10.1093/jac/dkz366.

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Abstract Objectives NDM carbapenemases have spread worldwide. However, little information exists about the impact of NDM-producing Enterobacteriaceae in Spain. By WGS, we sought to elucidate the population structure of NDM-like-producing Klebsiella pneumoniae and Escherichia coli in Spain and to determine the plasmids harbouring blaNDM-like genes. Methods High-resolution SNP typing, core-genome MLST and plasmid reconstruction (PlasmidID) were performed on 59 NDM-like-producing K. pneumoniae and 8 NDM-like-producing E. coli isolated over an 8 year period in Spain. Results Five major epidemic clones of NDM-producing K. pneumoniae caused five important nationwide outbreaks: ST437/NDM-7, ST437/NDM-1, ST147/NDM-1, ST11/NDM-1 and ST101/NDM-1; in contrast, the spread of NDM-producing E. coli was polyclonal. Three blaNDM types were identified: blaNDM-1, 61.2%; blaNDM-7, 32.8%; and blaNDM-5, 6%. Five K. pneumoniae isolates co-produced other carbapenemases (three blaOXA-48 and two blaVIM-1). The average number of acquired resistance genes was higher in K. pneumoniae than in E. coli. The plasmids encoding blaNDM-like genes belonged to IncFII, IncFIB, IncX3, IncR, IncN and IncC types, of which IncF, IncR and IncC were associated with MDR. The genetic surroundings of blaNDM-like genes showed a highly variable region upstream of ISAba125. Conclusions In recent years NDM-producing K. pneumoniae and E. coli have emerged in Spain; the spread of a few high-risk K. pneumoniae clones such as ST437/NDM-7, ST437/NDM-1, ST147/NDM-1, ST11/NDM-1 and ST101/NDM-1 have caused several interregional outbreaks. In contrast, the spread of NDM-producing E. coli has been polyclonal. Plasmid types IncFII, IncFIB, IncX3, IncR, IncN and IncC carried blaNDM, and the same IncX3 plasmid was detected in K. pneumoniae and E. coli.

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Marcoccia, Francesca, Carlo Bottoni, Alessia Sabatini, Martina Colapietro, Paola Sandra Mercuri, Moreno Galleni, Frédéric Kerff, et al. "Kinetic Study of Laboratory Mutants of NDM-1 Metallo-β-Lactamase and the Importance of an Isoleucine at Position 35." Antimicrobial Agents and Chemotherapy 60, no. 4 (February 8, 2016): 2366–72. http://dx.doi.org/10.1128/aac.00531-15.

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ABSTRACTTwo laboratory mutants of NDM-1 were generated by replacing the isoleucine at position 35 with threonine and serine residues: the NDM-1I35Tand NDM-1I35Senzymes. These mutants were well characterized, and their kinetic parameters were compared with those of the NDM-1 wild type. Thekcat,Km, andkcat/Kmvalues calculated for the two mutants were slightly different from those of the wild-type enzyme. Interestingly, thekcat/Kmof NDM-1I35Sfor loracarbef was about 14-fold higher than that of NDM-1. Far-UV circular dichroism (CD) spectra of NDM-1 and NDM-1I35Tand NDM-1I35Senzymes suggest local structural rearrangements in the secondary structure with a marked reduction of α-helix content in the mutants.

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Liu, Piccirilli, Liu, Li, Wang, and Shen. "Deciphering the Role of V88L Substitution in NDM-24 metallo-β-lactamase." Catalysts 9, no. 9 (September 2, 2019): 744. http://dx.doi.org/10.3390/catal9090744.

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: The New Delhi metallo-β-lactamase-1 (NDM-1) is a typical carbapenemase and plays a crucial role in antibiotic-resistance bacterial infection. Phylogenetic analysis, performed on known NDM-variants, classified NDM enzymes in seven clusters. Three of them include a major number of NDM-variants. In this study, we evaluated the role of the V88L substitution in NDM-24 by kinetical and structural analysis. Functional results showed that V88L did not significantly increase the resistance level in the NDM-24 transformant toward penicillins, cephalosporins, meropenem, and imipenem. Concerning ertapenem, E. coli DH5α/NDM-24 showed a MIC value 4-fold higher than that of E. coli DH5α/NDM-1. The determination of the kcat, Km, and kcat/Km values for NDM-24, compared with NDM-1 and NDM-5, demonstrated an increase of the substrate hydrolysis compared to all the β-lactams tested, except penicillins. The thermostability testing revealed that V88L generated a destabilized effect on NDM-24. The V88L substitution occurred in the β-strand and low β-sheet content in the secondary structure, as evidenced by the CD analysis data. In conclusion, the V88L substitution increases the enzyme activity and decreases the protein stability. This study characterizes the role of the V88L substitution in NDM-24 and provides insight about the NDM variants evolution.

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Du, Xiao-Xing, Jian-Feng Wang, Ying Fu, Feng Zhao, Yan Chen, Hai-Ping Wang, and Yun-Song Yu. "Genetic characteristics of bla NDM-1-positive plasmid in Citrobacter freundii isolate separated from a clinical infectious patient." Journal of Medical Microbiology 62, no. 9 (September 1, 2013): 1332–37. http://dx.doi.org/10.1099/jmm.0.057091-0.

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This study reports an infectious case involving an NDM-1-producing Citrobacter freundii and further explored the potential threat of the bla NDM-1 gene by analysing the characteristics of the NDM-1-encoding plasmid sequence. A bla NDM-1-positive C. freundii with high resistance to carbapenems was separated from a clinical patient suffering from a urinary tract infection. S1 nuclease-based plasmid analysis followed by Southern blot hybridization, a conjugation experiment and electrotransformation confirmed that the bla NDM-1 gene was located on a plasmid. High-throughput sequencing of the bla NDM-1-postive plasmid (pCFNDM-CN) showed that it was a 54 kb IncX-type plasmid and contained a backbone region and a variable region with two β-lactamase genes (bla NDM-1 and bla SHV-12). The NDM-1 composite transposon in the variable region was surrounded by IS26 and IS5-truncated ISAba125, and shared a high sequence similarity to the bla NDM-1 surrounding structure in Acinetobacter spp. Our research suggested that the NDM-1 composite transposon might play an essential role in mobilization of the bla NDM-1 gene from Acinetobacter spp. to Enterobacteriaceae.

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Kelsey, Jessica S., Nathan M. Fastman, Elizabeth F. Noratel, and Daphne D. Blumberg. "Ndm, a coiled-coil domain protein that suppresses macropinocytosis and has effects on cell migration." Molecular Biology of the Cell 23, no. 17 (September 2012): 3407–19. http://dx.doi.org/10.1091/mbc.e12-05-0392.

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The ampA gene has a role in cell migration in Dictyostelium discoideum. Cells overexpressing AmpA show an increase in cell migration, forming large plaques on bacterial lawns. A second-site suppressor of this ampA-overexpressing phenotype identified a previously uncharacterized gene, ndm, which is described here. The Ndm protein is predicted to contain a coiled-coil BAR-like domain—a domain involved in endocytosis and membrane bending. ndm-knockout and Ndm-monomeric red fluorescent protein–expressing cell lines were used to establish a role for ndm in suppressing endocytosis. An increase in the rate of endocytosis and in the number of endosomes was detected in ndm− cells. During migration ndm− cells formed numerous endocytic cups instead of the broad lamellipodia structure characteristic of moving cells. A second lamellipodia-based function—cell spreading—was also defective in the ndm− cells. The increase in endocytosis and the defect in lamellipodia formation were associated with reduced chemotaxis in ndm− cells. Immunofluorescence results and glutathione S-transferase pull-down assays revealed an association of Ndm with coronin and F-actin. The results establish ndm as a gene important in regulating the balance between formation of endocytic cups and lamellipodia structures.

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Rahman, Mohibur, Sanket Kumar Shukla, Kashi Nath Prasad, Cristina M. Ovejero, Binod Kumar Pati, Aparna Tripathi, Avinash Singh, Ashwini K. Srivastava, and Bruno Gonzalez-Zorn. "Prevalence and molecular characterisation of New Delhi metallo-β-lactamases NDM-1, NDM-5, NDM-6 and NDM-7 in multidrug-resistant Enterobacteriaceae from India." International Journal of Antimicrobial Agents 44, no. 1 (July 2014): 30–37. http://dx.doi.org/10.1016/j.ijantimicag.2014.03.003.

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Tada, Tatsuya, Basudha Shrestha, Tohru Miyoshi-Akiyama, Kayo Shimada, Hiroshi Ohara, Teruo Kirikae, and Bharat M. Pokhrel. "NDM-12, a Novel New Delhi Metallo-β-Lactamase Variant from a Carbapenem-Resistant Escherichia coli Clinical Isolate in Nepal." Antimicrobial Agents and Chemotherapy 58, no. 10 (August 4, 2014): 6302–5. http://dx.doi.org/10.1128/aac.03355-14.

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ABSTRACTA novel New Delhi metallo-β-lactamase variant, NDM-12, was identified in a carbapenem-resistantEscherichia coliclinical isolate obtained from a urine sample from a patient in Nepal. NDM-12 differed from NDM-1 by two amino acid substitutions (M154L and G222D). The enzymatic activities of NDM-12 against β-lactams were similar to those of NDM-1, although NDM-12 showed lowerkcat/Kmratios for all β-lactams tested except doripenem. TheblaNDM-12gene was located in a plasmid of 160 kb.

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Kim, So Yeon, Ji-Young Rhee, Sang Yop Shin, and Kwan Soo Ko. "Characteristics of community-onset NDM-1-producing Klebsiella pneumoniae isolates." Journal of Medical Microbiology 63, no. 1 (January 1, 2014): 86–89. http://dx.doi.org/10.1099/jmm.0.067744-0.

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Multilocus sequence typing and in vitro antimicrobial susceptibility testing were performed for three community-onset New Delhi metallo-β-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae isolates from Korea. The genetic structure surrounding the bla NDM-1 gene was determined in bla NDM-1-harbouring plasmids. Three NDM-1-producing K. pneumoniae isolates were found to belong to the same clone (sequence type 340). Each of these isolates showed the same genetic structure surrounding the bla NDM-1 gene. The genes bla NDM-1, ble MBL, trpF and dsbC were flanked by two intact insertion sequences, ISAba125 and IS26, which may promote horizontal gene transfer. The bla NDM-1-harbouring plasmids conferred antimicrobial resistance to carbapenems, cephalosporins, aminoglycosides and aztreonam in transconjugants. It can be speculated that either the entire bla NDM-1-harbouring plasmids or just the part of the plasmid containing the bla NDM-1 gene may have transferred between K. pneumoniae and Escherichia coli. Following the transfer, the isolate disseminated throughout Korea. This study suggests the need for monitoring the dissemination of NDM-1-producing isolates across countries or continents due to their potential transferability via ISAba125- and IS26-associated transposons.

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Tada, Tatsuya, Tohru Miyoshi-Akiyama, Rajan K. Dahal, Manoj K. Sah, Hiroshi Ohara, Teruo Kirikae, and Bharat M. Pokhrel. "NDM-8 Metallo-β-Lactamase in a Multidrug-Resistant Escherichia coli Strain Isolated in Nepal." Antimicrobial Agents and Chemotherapy 57, no. 5 (March 4, 2013): 2394–96. http://dx.doi.org/10.1128/aac.02553-12.

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ABSTRACTA novel metallo-β-lactamase, NDM-8, was identified in a multidrug-resistantEscherichia coliisolate, IOMTU11 (NCGM37), obtained from the respiratory tract of a patient in Nepal. The amino acid sequence of NDM-8 has substitutions at positions 130 (Asp to Gly) and 154 (Met to Leu) compared with NDM-1. NDM-8 showed enzymatic activities against β-lactams similar to those of NDM-1.

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Al Senani, Aisha, Nishath Hamza, Hanan Al Azkawi, Manal Al Kharusi, Nashat Al Sukaiti, Maryam Al Badi, Moza Al Yahyai, et al. "Genetic mutations associated with neonatal diabetes mellitus in Omani patients." Journal of Pediatric Endocrinology and Metabolism 31, no. 2 (January 26, 2018): 195–204. http://dx.doi.org/10.1515/jpem-2017-0284.

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Abstract Background: Neonatal diabetes mellitus (NDM) is a rare disorder worldwide where diabetes is diagnosed in the first 6 months of life. However, Oman has a relatively high incidence of NDM. Methods: In this study, we investigated the genetic etiologies underlying NDM and their prevalence in Oman. We collected a cohort of 24 NDM patients, with and without genetic diagnosis, referred to our center from 2007 to 2015. All patients without a genetic diagnosis were tested for mutations in 23 NDM-associated genes using a custom-targeted next-generation sequencing (NGS) panel and methylation analysis of the 6q24 locus. Results: A genetic abnormality was detected in 15/24 (62.5%) of our Omani NDM patients. We report the detection of 6q24 methylation abnormalities and KCNJ11 mutations for the first time in Omani NDM patients. Unlike Western populations where NDM is predominantly due to mutations in the KCNJ11, ABCC8 and INS genes, NDM due to homozygous GCK gene mutations were most prevalent in Oman, having been observed in seven out of 15 NDM patients in whom we established the genetic etiology. This reflects the high degree of consanguinity which makes recessive conditions more likely. Conclusions: The results of this study are likely to impact any future strategy to introduce genetic testing for NDM disorders within the national healthcare system in Oman.

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Wailan, Alexander M., Hanna E. Sidjabat, Wan Keat Yam, Nabil-Fareed Alikhan, Nicola K. Petty, Anna L. Sartor, Deborah A. Williamson, et al. "Mechanisms Involved in Acquisition ofblaNDMGenes by IncA/C2and IncFIIYPlasmids." Antimicrobial Agents and Chemotherapy 60, no. 7 (April 25, 2016): 4082–88. http://dx.doi.org/10.1128/aac.00368-16.

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ABSTRACTblaNDMgenes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying ablaNDMgene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of theblaNDMregion found onAcinetobacterplasmids. pKP1-NDM-1 and pEC2-NDM-3, fromKlebsiella pneumoniaeandEscherichia coli, respectively, were identified as type 1 IncA/C2plasmids with almost identical backbones. Different regions carryingblaNDMare inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1may have been involved in the acquisition ofblaNDM-3by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, fromEnterobacter cloacaeandE. coli, respectively, have similar IncFIIYbackbones, but different regions carryingblaNDMare found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition ofblaNDM-6by pEC4-NDM-6 and thermtC16S rRNA methylase gene by IncFIIYplasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquiredblaNDMgenes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission ofblaNDMgenes among species of theEnterobacteriaceaefamily.

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Baraniak, A., M. Machulska, D. Żabicka, E. Literacka, R. Izdebski, P. Urbanowicz, K. Bojarska, et al. "Towards endemicity: large-scale expansion of the NDM-1-producing Klebsiella pneumoniae ST11 lineage in Poland, 2015–16." Journal of Antimicrobial Chemotherapy 74, no. 11 (August 13, 2019): 3199–204. http://dx.doi.org/10.1093/jac/dkz315.

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AbstractObjectivesIn 2015 and 2016 Poland recorded rapid proliferation of New Delhi MBL (NDM)-producing Enterobacterales, with at least 470 and 1780 cases, respectively. We addressed the roles of the Klebsiella pneumoniae ST11 NDM-1 outbreak genotype, already spreading in 2012–14, and of newly imported organisms in this increase.MethodsThe study included 2136 NDM-positive isolates identified between April 2015 and December 2016, following transfer of patients with K. pneumoniae ST147 NDM-1 from Tunisia to Warsaw in March 2015. The isolates were screened by PCR mapping for variants of blaNDM-carrying Tn125-like elements. Selected isolates were typed by PFGE and MLST. NDM-encoding plasmids were analysed by nuclease S1/hybridization, transfer assays, PCR-based replicon typing and PCR mapping.ResultsThe organisms were mainly K. pneumoniae containing the Tn125A variant of the ST11 epidemic lineage (n = 2094; ∼98%). Their representatives were of the outbreak pulsotype and ST11, and produced NDM-1, encoded by specific IncFII (pKPX-1/pB-3002cz)-like plasmids. The isolates were recovered in 145 healthcare centres in 13/16 administrative regions, predominantly the Warsaw area. The ‘Tunisian’ genotype K. pneumoniae ST147 NDM-1 Tn125F comprised 18 isolates (0.8%) from eight institutions. The remaining 24 isolates, mostly K. pneumoniae and Escherichia coli of diverse STs, produced NDM-1 or NDM-5 specified by various Tn125 derivatives and plasmids.ConclusionsThe K. pneumoniae ST11 NDM-1 outbreak has dramatically expanded in Poland since 2012, which may bring about a countrywide endemic situation in the near future. In addition, the so-far limited K. pneumoniae ST147 NDM-1 outbreak plus multiple NDM imports from different countries were observed in 2015–16.

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Zou, Dayang, Yong Huang, Xiangna Zhao, Wei Liu, Derong Dong, Huan Li, Xuesong Wang, et al. "A Novel New Delhi Metallo-β-Lactamase Variant, NDM-14, Isolated in a Chinese Hospital Possesses Increased Enzymatic Activity against Carbapenems." Antimicrobial Agents and Chemotherapy 59, no. 4 (February 2, 2015): 2450–53. http://dx.doi.org/10.1128/aac.05168-14.

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ABSTRACTA novel New Delhi metallo-β-lactamase (NDM) variant, NDM-14, was identified in clinical isolateAcinetobacter lwoffiiJN49-1, which was recovered from an intensive care unit patient at a local hospital in China. NDM-14, which differs from other existing enzymes by an amino acid substitution at position 130 (Asp130Gly), possesses enzymatic activity toward carbapenems that is greater than that of NDM-1. Kinetic data indicate that NDM-14 has a higher affinity for imipenem and meropenem.

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Wang, Yanling, Xiaodi Sun, Fanrong Kong, Lining Xia, Xuming Deng, Dacheng Wang, and Jianfeng Wang. "Specific NDM-1 Inhibitor of Isoliquiritin Enhances the Activity of Meropenem against NDM-1-positive Enterobacteriaceae in vitro." International Journal of Environmental Research and Public Health 17, no. 6 (March 24, 2020): 2162. http://dx.doi.org/10.3390/ijerph17062162.

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NDM-1-positive Enterobacteriaceae have caused serious clinical infections, with high mortality rates. Carbapenem was the ultimate expectation for the treatment of such infections in clinical practice. However, since the discovery of plasmid-mediated New Delhi metallo-β-lactamase-1 (NDM-1), the efficient therapeutic effects of carbapenems have been increasingly restricted. Here, we identified isoliquiritin, a novel specific inhibitor of the NDM-1 enzyme that restored the activity of carbapenem against NDM-1-producing E. coli isolates and K. pneumoniae isolates without affecting the growth of bacteria. A checkerboard test, growth curve assays and time-kill assays confirmed the significant synergistic effect of isoliquiritin combined with meropenem in vitro. It is worth noting that isoliquiritin only inhibited the activity of NDM-1 and had no obvious inhibitory effect on other class B metallo-β-lactamases (VIM-1) or NDM-1 mutants (NDM-5). The FIC indices of meropenem with isoliquiritin on NDM-1-positive E. coli and K. pneumoniae were all less than 0.5. Isoliquiritin had no influences on the expression of NDM-1-positive strains at concentrations below 64 µg/mL. Collectively, our results show that isoliquiritin is a potential adjuvant therapy drug that could enhance the antibacterial effect of carbapenems, such as meropenem, on NDM-1-positive Enterobacteria and lay the foundation for subsequent clinical trials.

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BARROSO NETO, ANTÔNIO MOREIRA, RENATA FERNANDES DE MATOS, MARCELO DE SOUSA PINHEIRO, CÂNDIDA HERMÍNIA CAMPOS DE MAGALHÃES BERTINI, and JÚLIO CÉSAR DOVALE. "GENETIC VARIABILITY AND SELECTION OF EXTRA-EARLY COWPEA PROGENIES." Revista Caatinga 30, no. 3 (September 2017): 698–707. http://dx.doi.org/10.1590/1983-21252017v30n318rc.

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ABSTRACT The precocity of cowpea is important because it indicates the possibility of increasing and/or stabilizing production in regions with long periods of drought. The aim of this study was to evaluate genetic variability and select extra-early cowpea progenies. Fifteen F3:6 progenies were evaluated in 2014 while sixty-two F7 progenies were evaluated in 2015. Two commercial cultivars were used in experiments performed in the irrigated perimeter of Baixo Acaraú, in Marco, CE. The following characteristics were evaluated: number of days for flowering (NDF), number of days for maturity (NDM), plant height (PH), pod length (PL), number of seeds per pod (NSP), number of grains per plant (NGP), weight of 100 grains (W100G) and total weight (MTOT). Data were analyzed in lattice and RBD, according to the methodology of mixed models by the REML/BLUP procedure. Also, the components of variance and genetic values were estimated. Variability among progenies, high heritability and high accuracy were identified for all traits. For NDF and NDM, the progenies presented higher behavior than the controls. The lattice arrangement contributed to a greater gain with the selection of NDF, NDM, PH, NSP, NGP and WTOT. The genotypes 12, 15, 30, 33, 41, 43 and 52 are among the top ten because they have high genetic values in three or more traits. The genotypes 12, 15, 30, 33, 43 and 52 highlight extra-earliness (precocity).

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Nordmann, Patrice, Anne E. Boulanger, and Laurent Poirel. "NDM-4 Metallo-β-Lactamase with Increased Carbapenemase Activity from Escherichia coli." Antimicrobial Agents and Chemotherapy 56, no. 4 (January 17, 2012): 2184–86. http://dx.doi.org/10.1128/aac.05961-11.

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ABSTRACTA clinicalEscherichia coliisolate resistant to all β-lactams, including carbapenems, expressed a novel metallo-β-lactamase (MBL), NDM-4, differing from NDM-1 by a single amino acid substitution (Met154Leu). NDM-4 possessed increased hydrolytic activity toward carbapenems and several cephalosporins compared to that of NDM-1. This amino acid substitution was not located in the known active sites of NDM-1, indicating that remote amino acid substitutions might also play a role in the extended activity of this MBL.

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Xing, Yinting, Wei Yang, Yingyu Jin, and Yanhong Liu. "Neutrophil count multiplied by D-dimer combined with pneumonia may better predict short-term outcomes in patients with acute ischemic stroke." PLOS ONE 17, no. 10 (October 7, 2022): e0275350. http://dx.doi.org/10.1371/journal.pone.0275350.

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Objective To investigate the predictive value of neutrophil, D-dimer and diseases associated with stroke for short-term outcomes of acute ischemic stroke (AIS). Methods By collecting the subitems of laboratory data especially routine blood and coagulation test in AIS patients, and recording their clinical status, the correlation, regression and predictive value of each subitem with the short-term outcomes of AIS were analyzed. The predict model was constructed. Results The neutrophil count multiplied by D-dimer (NDM) had the best predictive value among the subitems, and the area under the receiver operating characteristic (ROC) curve reached 0.804. When clinical information was not considered, the Youden index of NDM was calculated to be 0.48, corresponding to an NDM value of 7.78, a diagnostic sensitivity of 0.79, specificity of 0.69, negative predictive value of 96%. NDM were divided into 5 quintiles, the five grade of NDM (quintile) were < = 1.82, 1.83–2.41, 2.42–3.27, 3.28–4.49, 4.95+, respectively. The multivariate regression analysis was conducted between NDM (quintile), Babinski+, pneumonia, cardiac disease and poor outcomes of AIS. Compared with the first grade of NDM (quintile), the second grade of NDM (quintile) was not significant, but the third grade of NDM (quintile) showed 7.061 times, the fourth grade of NDM (quintile) showed 11.776 times, the fifth grade of NDM (quintile) showed 23.394 times in short-term poor outcomes occurrence. Babinski sign + showed 1.512 times, pneumonia showed 2.995 times, cardiac disease showed 1.936 times in short-term poor outcomes occurrence compared with those negative patients. Conclusions NDM combined with pneumonia may better predict short-term outcomes in patients with AIS. Early prevention, regular examination and timely intervention should be emphasized for patients, which may reduce the risk of short-term poor outcomes.

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Wang, Xiyan, Yanan Yang, Yawen Gao, and Xiaodi Niu. "Discovery of the Novel Inhibitor Against New Delhi Metallo-β-Lactamase Based on Virtual Screening and Molecular Modelling." International Journal of Molecular Sciences 21, no. 10 (May 18, 2020): 3567. http://dx.doi.org/10.3390/ijms21103567.

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New Delhi metallo-β-lactamase (NDM-1), one of the metallo-β-lactamases (MBLs), leads to antibiotic resistance in clinical treatments due to the strong ability of hydrolysis to almost all kinds of β-lactam antibiotics. Therefore, there is the urgent need for the research and development of the novel drug-resistant inhibitors targeting NDM-1. In this study, ZINC05683641 was screened as potential NDM-1 inhibitor by virtual screening and the inhibitor mechanism of this compound was explored based on molecular dynamics simulation. The nitrocefin assay showed that the IC50 value of ZINC05683641 was 13.59 ± 0.52 μM, indicating that the hydrolytic activity of NDM-1 can be obviously suppressed by ZINC05683641. Further, the binding mode of ZINC05683641 with NDM-1 was obtained by molecular modeling, binding free energy calculation, mutagenesis assays and fluorescence-quenching assays. As results, ILE-35, MET-67, VAL-73, TRP-93, CYS-208, ASN-220 and HIS-250 played the key roles in the binding of NDM-1 with ZINC05683641. Interestingly, these key residues were exactly located in the catalytic activity region of NDM-1, implying that the inhibitor mechanism of ZINC05683641 against NDM-1 was the competitive inhibition. These findings will provide an available approach to research and develop new drug against NDM-1 and treatment for bacterial resistance.

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Destro, Deonisio, Henrique Stoco Bizeti, Leandro Anderlin Garcia, Inês Cristina de Batista Fonseca, Ricardo Montalván, and Édison Miglioranza. "Comparison between the SPD and the SPDS methods for segregating generation advancement in soybean." Brazilian Archives of Biology and Technology 46, no. 4 (December 2003): 545–51. http://dx.doi.org/10.1590/s1516-89132003000400008.

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The purpose of this work was to compare the SPD (Single Pod Descent) and SPDS (Single Pod Descent with Selection) methods for segregating generation advancement in soybean breeding. Sixteen populations derived from crosses among Japanese and adapted Brazilian soybean were used. The traits, number of days to flowering (NDF) and to maturity (NDM), plant height at flowering (PHF) and at maturity (PHM), and individual plant yield (IPY) were assessed. The populations obtained by SPDS showed values close to the variation in the populations obtained by SPD. Regression through the origin showed that both methods were equivalent for NDM in the F3 generation and for NDF in the F4 generation. For all other trait/generation combinations, SPDS yielded superior means. Therefore, it was preferable to use SPDS because it allowed the advance of generations with smaller population size.

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Garg, Atul, and Jaya Garg. "Dissemination of NDM-1." Lancet Infectious Diseases 12, no. 2 (February 2012): 99. http://dx.doi.org/10.1016/s1473-3099(11)70237-7.

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Hasan, Badrul, Peter Drobni, Mirva Drobni, Munirul Alam, and Björn Olsen. "Dissemination of NDM-1." Lancet Infectious Diseases 12, no. 2 (February 2012): 99–100. http://dx.doi.org/10.1016/s1473-3099(11)70333-4.

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Sahai, Sanjeev. "Dissemination of NDM-1." Lancet Infectious Diseases 12, no. 2 (February 2012): 100–101. http://dx.doi.org/10.1016/s1473-3099(11)70334-6.

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Nordmann, Patrice, Laurent Poirel, Timothy R. Walsh, and David M. Livermore. "The emerging NDM carbapenemases." Trends in Microbiology 19, no. 12 (December 2011): 588–95. http://dx.doi.org/10.1016/j.tim.2011.09.005.

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Kim, Youngchang, Mark Cunningham, Christine Tesar, Robert Jedrzejczak, Joseph Mire, Andrew Binkowski, Gyorgy Babnigg, James Sacchettini, and Andrzej Joachimiak. "Carbapenemase NDM-1, Structural Analysis of the Catalytic Mechanism." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C818. http://dx.doi.org/10.1107/s2053273314091815.

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The New Delhi Metallo β-lactamase (NDM-1), first identified in Klebsiella pneumoniae has been shown to hydrolyze nearly all clinical β-lactam antibiotics including carbapenems, considered "last resort" antibiotics. Its gene resides on mobile plasmids that move between different strains of bacteria posing a serious global threat to human health. There have also been reports of several variants, up to NDM-9, some with increased carbapenemase activity. As part of the NIGMS PSI:Biology effort, the Midwest Center for Structural Genomics (MCSG) together with the Structures of Mtb Proteins Conferring Susceptibility to Known Mtb Inhibitors partnership, made significant progress in investigating the enzyme atomic structure and catalytic mechanism. A large number of protein constructs as well as mutants were made and a number of high-resolution structures of NDM-1 (no Zn, one Zn, two Zn, two Mn or Cd, and complexed with antibiotics) and NDM-1 variants, NDM-2, NDM-3, NDM-4, NDM-5 and NDM-6 have been determined. We have determined the two structures of Michaelis complex: NDM-1 with two cadmium ions and a mixture of hydrolyzed and unhydrolyzed ampicillin (1.50 Å) and one with two cadmium ions and partly hydrolyzed faropenem (2.00 Å). The crystal structures revealed a ligand-binding pocket consisting of several flexible loops capable of accommodating many β-lactam substrates of different sizes and shapes. The structures with various metals suggest that the distance between the two metal atoms is closely correlated with substrate binding efficiency and hydrolysis and the pH-dependency of catalytic activity. For better understanding of catalytic mechanism of NDM-1, particularly the dynamics of substrate binding and the energy surfaces along the suggested reaction pathways, molecular dynamics calculations and hybrid classical/quantum (QM/MM) calculations were performed. This work was supported by NIH Grant GM094585 and by the U.S. DOE, OBER contract DE-AC02-06CH11357

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Fiett, J., A. Baraniak, R. Izdebski, I. Sitkiewicz, D. Żabicka, A. Meler, K. Filczak, W. Hryniewicz, and M. Gniadkowski. "The First NDM Metallo-β-Lactamase-Producing Enterobacteriaceae Isolate in Poland: Evolution of IncFII-Type Plasmids Carrying theblaNDM-1Gene." Antimicrobial Agents and Chemotherapy 58, no. 2 (November 18, 2013): 1203–7. http://dx.doi.org/10.1128/aac.01197-13.

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ABSTRACTPoland's firstEnterobacteriaceaeisolate producing the New Delhi metallo-β-lactamase (NDM) was identified in August 2011.Escherichia colisequence type ST410 NDM-1 was cultured from a critically ill patient who had been transferred directly from the Congo. TheblaNDM-1gene was carried by conjugative IncFII-type plasmid pMC-NDM (87,619 bp), which showed structural similarity to plasmid pGUE-NDM, which was identified earlier in France in anE. coliST131 isolate of Indian origin.

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Chew, Ka Lip, Sophie Octavia, Oon Tek Ng, Kalisvar Marimuthu, Indumathi Venkatachalam, Bernadette Cheng, Raymond T. P. Lin, and Jeanette W. P. Teo. "Challenge of drug resistance in Pseudomonas aeruginosa: clonal spread of NDM-1-positive ST-308 within a tertiary hospital." Journal of Antimicrobial Chemotherapy 74, no. 8 (May 12, 2019): 2220–24. http://dx.doi.org/10.1093/jac/dkz169.

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Abstract Objectives MDR Pseudomonas aeruginosa is a serious global threat to healthcare institutions. The mechanism by which drug resistance can be acquired is variable, but acquired carbapenemase production has been reported in P. aeruginosa. An investigation was performed to determine the rate and genomic epidemiology of New Delhi MBL (NDM) in β-lactam-non-susceptible isolates. Methods P. aeruginosa isolates from a tertiary hospital in Singapore between January 2015 and February 2018 were investigated for the presence of NDM genes. Results Out of 298 pan-β-lactam-non-susceptible isolates, 31 were found to be NDM positive (10.4%). WGS demonstrated that all 31 NDM-positive isolates were clonal, belonging to ST-308. blaNDM was chromosomally inserted within an integrative and conjugative element (ICE), ICETn43716385. The NDM-P. aeruginosa isolates possessed an extensive repertoire of both cell-associated [flagella, pili, alginate/biofilm, LPS, type III secretion system (T3SS) and type VI secretion system (T6SS)] and secreted virulence factors. Antibiograms revealed higher rates of drug resistance in NDM-positive isolates compared with their non-NDM counterparts. The NDM isolates remained 100% susceptible only to colistin. Conclusions The combination of chromosomal mutations, acquired resistance genes and virulence factors likely facilitated the persistent and ongoing spread of the ST-308 clade of P. aeruginosa within the hospital. Our study illustrates the particular threat of NDM-positive P. aeruginosa in a tertiary hospital setting in the era of antimicrobial resistance.

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Zhou, Zhenwen, Ruili Guan, Yiyu Yang, Ling Chen, Jie Fu, Qiulian Deng, Yongqiang Xie, et al. "Identification of New Delhi metallo-β-lactamase gene (NDM-1) from a clinical isolate of Acinetobacter junii in China." Canadian Journal of Microbiology 58, no. 1 (January 2012): 112–15. http://dx.doi.org/10.1139/w11-112.

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New Delhi metallo-β-lactamase-1 (NDM-1) is a novel type of metallo-β-lactamase (MBL) responsible for bacterial resistance to β-lactam antibiotics. Acinetobacter junii was previously shown to possess a MBL phenotype; however, the genes responsible for this phenotype were not identified. In this study, we reported the identification of NDM-1 gene in a clinical isolate of A. junii from a child patient in China, which was resistant to all β-lactams except aztreonam but sensitive to aminoglycosides and quinolones. The cloned NDM-1 gene contained an open reading frame of 813 bp and had a nucleotide sequence 99.9% identical (812/813) to reported NDM-1 genes carried by Acinetobacter baumannii , Enterococcus faecium , Escherichia coli , and Klebsiella pneumoniae . Recombinant NDM-1 protein was successfully expressed in E. coli BL21, and antibiotic sensitivities of the NDM-1-producing E. coli were largely similar to the A. junii 1454 isolate. The findings of this study raise attention to the emergence and spread of NDM-1-carrying bacteria in China.

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Shugart, Alicia, Garrett Mahon, Lauren Epstein, Jennifer Y. Huang, Gillian McAllister, Adrian Lawsin, Erisa Sula, et al. "Changing US Epidemiology of NDM-Producing Carbapenem-Resistant Enterobacteriaceae, 2017–2019." Infection Control & Hospital Epidemiology 41, S1 (October 2020): s25—s26. http://dx.doi.org/10.1017/ice.2020.502.

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Background: Due to limited therapeutic options and potential for spread, carbapenem-resistant Enterobacteriaceae (CRE)-producing New Delhi metallo-β-lactamases (NDMs) are a public health priority. We investigated the epidemiology of NDM-producing CRE reported to the CDC to clarify its distribution and relative prevalence. Methods: The CDC’s Antibiotic Resistance Laboratory Network supports molecular testing of CRE for 5 carbapenemases nationally. Although KPC is the most common carbapenemase in the United States, non-KPC carbapenemases are a growing concern. We analyzed CRE with any of 4 non-KPC plasmid-mediated carbapenemases (NDM, VIM, IMP, or OXA-48 type) isolated from specimens collected from January 1, 2017, through June 30, 2019; only a patient’s first isolate per organism–carbapenemase combination was included. We excluded isolates from specimen sources associated with colonization screening (eg, perirectal). We compared the proportion of NDM-producing CRE to all non-KPC–producing CP-CRE between period A (January to June 2018) and period B (January to June 2019). Health departments and the CDC collected additional exposure and molecular information in selected states to better describe current NDM-producing CRE epidemiology. Results: Overall, 47 states reported 1,013 non–KPC-producing CP-CRE (range/state, 1–109 isolates; median, 11 isolates); 46 states reported 631 NDM-producing CRE (range/state, 1–84; median, 6). NDM-producing CRE increased quarterly from the third quarter of 2018 through the second quarter of 2019; CP-CRE isolates with other non-KPC carbapenemases remained stable (Fig. 1). In period A, 124 of 216 emerging CP-CRE had NDM (57.1%), compared with 255 of 359 emerging CP-CRE (71.0%) during period B (P = .1179). Among NDM-producing CRE, the proportion of Enterobacter spp increased from 10.5% in 2018 to 18.4% in 2019 (P = .0467) (Fig. 2). In total, 18 states reported more NDM-producing CRE in the first 6 months of 2019 than in all of 2018. Connecticut, Ohio, and Oregon were among states that conducted detailed investigations; these 3 states identified 24 NDM-producing CRE isolates from 23 patients in period B. Overall, 5 (21.7%) of 22 patients with history available traveled internationally ≤12 months prior to culture; 17 (73.9%) acquired NDM-producing CRE domestically. Among 15 isolates sequenced, 8 (53.3%) carried NDM-5 (6 E. coli, 1 Enterobacter spp and 1 Klebsiella spp) and 7 (46.7%) carried NDM-1 (6 Enterobacter spp and 1 Klebsiella spp). Species were diverse; no single strain type was shared by >2 isolates. Conclusions: Detection of NDM-producing CRE has increased across the AR Lab Network. Among states with detailed information available, domestic acquisition was common, and no single variant or strain predominated. Aggressive public health response and further understanding of current US NDM-CRE epidemiology are needed to prevent further spread.Disclosures: NoneFunding: None

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Shrestha, Basudha, Tatsuya Tada, Tohru Miyoshi-Akiyama, Kayo Shimada, Hiroshi Ohara, Teruo Kirikae, and Bharat M. Pokhrel. "Identification of a Novel NDM Variant, NDM-13, from a Multidrug-Resistant Escherichia coli Clinical Isolate in Nepal." Antimicrobial Agents and Chemotherapy 59, no. 9 (July 13, 2015): 5847–50. http://dx.doi.org/10.1128/aac.00332-15.

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ABSTRACTA novel New Delhi metallo-β-lactamase, NDM-13, was identified in a carbapenem-resistantEscherichia coliclinical isolate obtained from the urine of a patient in Nepal. The enzymatic activity of NDM-13 against β-lactams was similar to that of NDM-1. However, NDM-13 displayed significantly higherkcat/Kmratios for cefotaxime. The genetic environment ofblaNDM-13was determined to betnpA-IS30-blaNDM-13-bleMBL-trpF-dsbC-cutA-groES-groL, withblaNDM-13located within the chromosome.

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Seo, Hyeonji, Min Jae Kim, Yong Pil Chong, Sung-Han Kim, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, and Jiwon Jung. "835. Comparison of the outcomes of patients with KPC and NDM-1-producing Enterobacteriaceae." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S458—S459. http://dx.doi.org/10.1093/ofid/ofaa439.1024.

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Abstract Background Carbapenemase-producing Enterobacteriaceae infections are associated with high mortality. We aimed to compare the clinical outcomes of patients with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and those with New-Delhi-Metallo-beta-lactamase-1 (NDM-1)-producing Enterobacteriaceae. Methods We performed a retrospective cohort study of all adult patients (> 16 years old) with KPC or NDM-1-producing Enterobacteriaceae isolates in a 2,700-bed tertiary referral hospital in Seoul, South Korea between 2010 and 2019. Primary outcomes were infection within 30 days and 30-day mortality after the first isolation of KPC or NDM-1-producing Enterobacteriaceae. Results A total of 859 patients were identified during the study period. Of them, 475 (55%) were KPC group and 384 (45%) were NDM-1 group. KPC group tended to develop infection within 30 days after first isolation more frequently than NDM-1 group (31% vs. 26%; P = 0.07). Thirty-day mortality was significantly higher in KPC group compared to NDM-1 group (KPC, 17% (81/475) versus NDM-1, 9% (33/384), P < 0.001). Multivariate analysis revealed that APACHE II score (adjusted odds ratio [aOR], 1.12; P < 0.001), solid cancer (aOR, 2.56; P < 0.001), previous carbapenem therapy (aOR, 1.93; P = 0.004), development of infection of KPC or NDM-1-producing Enterobacteriaceae within 30 days (aOR, 2.63; P < 0.001), and KPC-producing Enterobacteriaceae (aOR, 1.62; P = 0.045) were independent risk factors for 30-day mortality. Table 1. Results of analyses of risk factors for 30-day mortality from initial positive culture date in patients with KPC or NDM-1- producing Enterobacteriaceae Figure 1. Kaplan–Meier survival estimates of patients with KPC or NDM-1-producing Enterobacteriaceae for 30-day mortality after first isolation: KPC (continuous line) versus NDM (dotted line). (log-rank test). Conclusion Our study suggests that KPC-producing Enterobacteriaceae is associated with poorer outcome compared to NDM-1-producing Enterobacteriaceae. Therefore, patients with KPC-producing Enterobacteriaceae colonization should be monitored carefully for development of infection, and appropriate antibiotics should be initiated as soon as possible. Disclosures All Authors: No reported disclosures

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Santhanam, Amutha. "Whole Genomic analysis of a clinical isolate of Uropathogenic Escherichia coli strain of Sequence Type - 101 carrying the drug resistance NDM-7 in IncX3 plasmid." Bioinformation 17, no. 1 (January 31, 2021): 126–31. http://dx.doi.org/10.6026/97320630017126.

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The emerging NDM-producing Enterobactereciae is a major threat to public health. The association of NDM-7 with sequence type 101 E. coli is identified in very few numbers. Therefore, it is of interest to analyse the whole genome sequence of NDM-producing uropathogenic E. coli XA31 that was found to carry numerous drug resistance genes of different antibiotic classes. The isolate E. coli belongs to ST-101 carrying blaNDM-7 coexisting with several resistance genes blaOXA-1, blaTEM1-A, blaCTX-M15, aac(6')-Ib-cr, catB3, tetB. Resfinder predicts this and four other plasmid replicons were identified using the Plasfinder in the CGE platform. The high transferable IncX3 plasmid was found to carry the NDM-7 gene. Thus, we the report the combination of NDM-7-ST101-IncX3 in India. The combination of this epidemic clone with NDM-7 is highly required to develop an effective infection control strategy.

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Peirano, Gisele, Paul C. Schreckenberger, and Johann D. D. Pitout. "Characteristics of NDM-1-Producing Escherichia coli Isolates That Belong to the Successful and Virulent Clone ST131." Antimicrobial Agents and Chemotherapy 55, no. 6 (March 28, 2011): 2986–88. http://dx.doi.org/10.1128/aac.01763-10.

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ABSTRACTAn NDM-1 carbapenemase-producingEscherichia coliisolate of sequence type 131 (ST131) that belonged to phylogenetic group B2 was obtained from a patient with a urinary tract infection who returned to the United States after a recent hospitalization while visiting India. NDM-1-producingE. coliST131 had significantly more virulence factors than NDM-1-producingE. coliST101, previously isolated from a patient in Canada. The presence of NDM β-lactamases in a very successful and virulentE. colisequence type is of concern.

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Hoffman, Robert R., and Gary L. Klein. "Challenges and Prospects for the Paradigm of Naturalistic Decision Making." Journal of Cognitive Engineering and Decision Making 11, no. 1 (February 2, 2017): 97–104. http://dx.doi.org/10.1177/1555343416689646.

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This is a report on developments in naturalistic decision making (NDM) with respect to current challenges and prospects discussed at the 2015 NDM International Conference. Emphasis is placed on orienting scientific resources to address the challenges expressed by the Human Systems Priority Steering Council. Participants and presenters at the NDM conference were asked to discuss ways in which the NDM paradigm can be extended and applied to address current and emerging national, international, and societal challenges.

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Khong, Wei Xin, Kalisvar Marimuthu, Jeanette Teo, Yichen Ding, Eryu Xia, Jia Jun Lee, Rick Twee-Hee Ong, et al. "Tracking inter-institutional spread of NDM and identification of a novel NDM-positive plasmid, pSg1-NDM, using next-generation sequencing approaches." Journal of Antimicrobial Chemotherapy 71, no. 11 (August 2, 2016): 3081–89. http://dx.doi.org/10.1093/jac/dkw277.

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Chen, Cheng, Ke-Wu Yang, Lin-Yu Wu, Jia-Qi Li, and Le-Yun Sun. "Disulfiram as a potent metallo-β-lactamase inhibitor with dual functional mechanisms." Chemical Communications 56, no. 18 (2020): 2755–58. http://dx.doi.org/10.1039/c9cc09074f.

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We report a promising NDM-1 inhibitor, disulfiram, which can covalently bind to NDM-1 by forming an S–S bond with the Cys208 residue. Cu(DTC)₂ also inactivated NDM-1 through oxidizing the Zn(ii) thiolate site of the enzyme.

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MacVane, Shawn H., Jared L. Crandon, Wright W. Nichols, and David P. Nicolau. "UnexpectedIn VivoActivity of Ceftazidime Alone and in Combination with Avibactam against New Delhi Metallo-β-Lactamase-Producing Enterobacteriaceae in a Murine Thigh Infection Model." Antimicrobial Agents and Chemotherapy 58, no. 11 (September 15, 2014): 7007–9. http://dx.doi.org/10.1128/aac.02662-14.

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ABSTRACTThe emergence of the New Delhi metallo-β-lactamase (NDM) amongEnterobacteriaceaehas become a global concern because of its high levels ofin vitroresistance to nearly all available antibiotics. However, recentin vivostudies demonstrated the efficacies of carbapenems against NDM-1-producing isolates despite high MICs. Herein, we reportin vivofindings with ceftazidime and ceftazidime-avibactam against an isogenic pair (wild type and NDM-1) and four clinical NDM-producing isolates that demonstrate discordance between MICs measuredin vitroand thein vivoactivity of ceftazidime-avibactam against this resistant genotype.

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Tada, Tatsuya, Tohru Miyoshi-Akiyama, Kayo Shimada, and Teruo Kirikae. "Biochemical Analysis of Metallo-β-Lactamase NDM-3 from a Multidrug-Resistant Escherichia coli Strain Isolated in Japan." Antimicrobial Agents and Chemotherapy 58, no. 6 (March 31, 2014): 3538–40. http://dx.doi.org/10.1128/aac.02793-13.

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ABSTRACTNew Delhi metallo-β-lactamase-3 (NDM-3) was identified in a multidrug-resistantEscherichia coliisolate, NCGM77, obtained from the feces of a patient in Japan. The enzymatic activities of NDM-3 against β-lactams were similar to those of NDM-1, although NDM-3 showed slightly lowerkcat/Kmratios for all the β-lactams tested except for doripenem. The genetic context forblaNDM-3wastnpA-blaNDM-3-bleMBL-trpF-dsbC-tnpA-sulI-qacEdeltaI-aadA2-dfrA1, which was present on an approximately 250-kb plasmid.

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Xuan, Junji, Bingzhi Li, Likun Xu, Zhaoqi Zhang, Yonglei Xin, Lili Xue, and Li Li. "Performance of SS304 Modified by Silver Micro/Nano-Dendrite Coating with Hot-Water Super-Repellency in Simulated PEMFC Cathode Environment." Nanomaterials 12, no. 10 (May 18, 2022): 1726. http://dx.doi.org/10.3390/nano12101726.

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In this study, an silver (Ag) plating with micro/nano-dendrite structures is prepared on the 304 stainless steel (SS304) surface by potentiostatic deposition (Ag/SS304). After being modified by n-dodecyl mercaptan (NDM) with the low surface energy, the obtained sample (NDM@Ag/SS304) exhibits stable superhydrophobicity and excellent hot-water repellency. The surface morphology and composition of NDM@Ag/SS304 are analyzed by scanning electron microscope (SEM), X-ray spectrometer (EDS), X-ray diffractometer (XRD), and X-ray photoelectron spectrometer (XPS) characterization. The electrochemical measurements, tests of water contact angle (WCA), and interfacial contact resistance (ICR) are employed to systematically study the performance of the NDM@Ag/SS304 in the simulated cathode environment of proton exchange membrane fuel cell (PEMFC). The results show that the NDM@Ag/SS304 has high corrosion potential (~0.25 V) and low corrosion current density (~4.04 μA/cm2); after potentiostatic polarization (0.6 V, 5 h), the NDM@Ag/SS304 also shows high superhydrophobic stability.

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Ulloa, Erlinda R., Nicholas Dillon, Hannah Tsunemoto, Joe Pogliano, George Sakoulas, and Victor Nizet. "Avibactam Sensitizes Carbapenem-Resistant NDM-1–Producing Klebsiella pneumoniae to Innate Immune Clearance." Journal of Infectious Diseases 220, no. 3 (March 29, 2019): 484–93. http://dx.doi.org/10.1093/infdis/jiz128.

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AbstractInfections caused by New Delhi metallo-β-lactamase (NDM)–producing strains of multidrug-resistant Klebsiella pneumoniae are a global public health threat lacking reliable therapies. NDM is impervious to all existing β-lactamase inhibitor (BLI) drugs, including the non–β-lactam BLI avibactam (AVI). Though lacking direct activity against NDMs, AVI can interact with penicillin-binding protein 2 in a manner that may influence cell wall dynamics. We found that exposure of NDM-1–producing K. pneumoniae to AVI led to striking bactericidal interactions with human cathelicidin antimicrobial peptide LL-37, a frontline component of host innate immunity. Moreover, AVI markedly sensitized NDM-1–producing K. pneumoniae to killing by freshly isolated human neutrophils, platelets, and serum when complement was active. Finally, AVI monotherapy reduced lung counts of NDM-1–producing K. pneumoniae in a murine pulmonary challenge model. AVI sensitizes NDM-1–producing K. pneumoniae to innate immune clearance in ways that are not appreciated by standard antibiotic testing and that merit further study.

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Usman Qamar, Muhammad, Bruno S Lopes, Brekhna Hassan, Mohsin Khurshid, Muhammad Shafique, Muhammad Atif Nisar, Mashkoor Mohsin, et al. "The present danger of New Delhi metallo-β-lactamase: a threat to public health." Future Microbiology 15, no. 18 (December 2020): 1759–78. http://dx.doi.org/10.2217/fmb-2020-0069.

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The evolution of antimicrobial-resistant Gram-negative pathogens is a substantial menace to public health sectors, notably in developing countries because of the scarcity of healthcare facilities. New Delhi metallo-β-lactamase (NDM) is a potent β-lactam enzyme able to hydrolyze several available antibiotics. NDM was identified from the clinical isolates of Klebsiella pneumoniae and Escherichia coli from a Swedish patient in New Delhi, India. This enzyme horizontally passed on to various Gram-negative bacteria developing resistance against a variety of antibiotics which cause treatment crucial. These bacteria increase fatality rates and play an integral role in the economic burden. The efficient management of NDM-producing isolates requires the coordination between each healthcare setting in a region. In this review, we present the prevalence of NDM in children, fatality and the economic burden of resistant bacteria, the clonal spread of NDM harboring bacteria and modern techniques for the detection of NDM producing pathogens.

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Yang, Kai, Shumin Liu, Huanqin Li, Na Du, Jing Yao, Qiuyue He, and Yan Du. "NDM-1-Positive K. pneumoniae at a Teaching Hospital in Southwestern China: Clinical Characteristics, Antimicrobial Resistance, Molecular Characterization, Biofilm Assay, and Virulence." Canadian Journal of Infectious Diseases and Medical Microbiology 2020 (October 9, 2020): 1–9. http://dx.doi.org/10.1155/2020/9091360.

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Background. The emergence of the NDM-1-positive Klebsiella pneumoniae (K. pneumoniae) strains has led to limited therapeutic options for clinical treatment. Understanding the clinical characteristics, antimicrobial resistance, biofilm assay, and the virulence genes of these isolated strains is of great significance. Methods. The polymerase chain reaction (PCR) was used to screen isolated NDM-1-positive K. pneumoniae. The clinical information of the patients was collected from medical records. The NDM-1-positive K. pneumoniae isolates were subjected to antimicrobial susceptibility testing and multilocus sequence typing. Sixty strains of NDM-1-negative K. pneumoniae isolated during the same period were collected as the control group for the virulence analysis. The virulence phenotype of the strains was preliminarily evaluated by the string test and crystal violet semiquantitative biofilm formation experiment. PCR combined with gene sequencing was used to detect common high toxicity capsule genes (K1, K2, K5, K20, K54, and K57) and common virulence-related genes (entB, ybtS, ureA, ycf, WabG, FimH, uge, iutA, KfuB, aerobactin, rmpA, magA, Alls, IrnN, and VatD). Results. In the 30 nonduplicated NDM-1-positive K. pneumoniae isolates, 43.33% (13/30) of the patients had a history of a stay in the neonatal intensive care unit (NICU). All of the isolates exhibited multidrug resistance. Nine STs were identified, 77% (10/13) strains from the NICU were ST11. The NDM-1-positive K. pneumoniae string tests were all negative, and 35% (21/60) NDM-1-negative K. pneumoniae were positive. The ratios of NDM-1-positive K. pneumoniae isolates biofilm formation ability according to strong, medium, and weak classification were 67%, 23%, and 10%, respectively. NDM-1-negative K. pneumoniae isolates were 60%, 25%, and 15%, respectively. There was no statistical difference between the two groups (t = 0.61, P=0.2723). The virulence-associated genes with more than 80% of detection rates among the 30 NDM-1-positive K. pneumoniae isolates included entB (100%, 30/30), ybtS (93.33%, 28/30), ureA (90%, 27/30), ycf (83.33%, 25/30), and wabG (90%, 27/30). KfuB and iutA were detected at prevalence of 3.33% and 13.33%. vatD, allS, iroN, aerobactin, and rmpA were not detected. In the NDM-1-negative K. pneumoniae, all other 14 virulence genes except VatD were detected. After statistical analysis, FimH, WabG, ycf, iutA, kfuB, aerobactin, rmpA, and Alls virulence genes, P<0.005, there was a statistical difference. Conclusion. NDM-1-positive K. pneumoniae exhibited multidrug resistance, MLST typing is mainly ST11, there is small clonal dissemination in the NICU in the hospital, and the NDM-1-positive K. pneumoniae virulence genes carrier rate is lower than the NDM-1-negative K. pneumoniae virulence genes carrier rate.

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Taing, Meng-Wong, Jean-Thomas Pierson, Paul N. Shaw, Ralf G. Dietzgen, Sarah J. Roberts-Thomson, Michael J. Gidley, and Gregory R. Monteith. "Mango Fruit Extracts Differentially Affect Proliferation and Intracellular Calcium Signalling in MCF-7 Human Breast Cancer Cells." Journal of Chemistry 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/613268.

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The assessment of human cancer cell proliferation is a common approach in identifying plant extracts that have potential bioactive effects. In this study, we tested the hypothesis that methanolic extracts of peel and flesh from three archetypal mango cultivars, Irwin (IW), Nam Doc Mai (NDM), and Kensington Pride (KP), differentially affect proliferation, extracellular signal-regulated kinase (ERK) activity, and intracellular calcium ([Ca2+]I) signalling in MCF-7 human breast cancer cells. Mango flesh extracts from all three cultivars did not inhibit cell growth, and of the peel extracts only NDM reduced MCF-7 cell proliferation. Mango cultivar peel and flesh extracts did not significantly change ERK phosphorylation compared to controls; however, some reduced relative maximal peak[Ca2+]Iafter adenosine triphosphate stimulation, with NDM peel extract having the greatest effect among the treatments. Our results identify mango interfruit and intrafruit (peel and flesh) extract variability in antiproliferative effects and[Ca2+]Isignalling in MCF-7 breast cancer cells and highlight that parts of the fruit (such as peel and flesh) and cultivar differences are important factors to consider when assessing potential chemopreventive bioactive compounds in plants extracts.

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Rehman, Md, Mohamed AlAjmi, Afzal Hussain, Gulam Rather, and Meraj Khan. "High-Throughput Virtual Screening, Molecular Dynamics Simulation, and Enzyme Kinetics Identified ZINC84525623 as a Potential Inhibitor of NDM-1." International Journal of Molecular Sciences 20, no. 4 (February 14, 2019): 819. http://dx.doi.org/10.3390/ijms20040819.

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The bacteria expressing New Delhi Metallo-β-lactamase-1 (NDM-1) can hydrolyze all β-lactam antibiotics including carbapenems, causing multi-drug resistance. The worldwide emergence and dissemination of gene blaNDM-1 (produces NDM-1) in hospital and community settings, rising problems for public health. Indeed, there is an urgent need for NDM-1 inhibitors to manage antibiotic resistance. Here, we have identified novel non-β-lactam ring-containing inhibitors of NDM-1 by applying a high-throughput virtual screening of lead-like subset of ZINC database. The screened compounds were followed for the molecular docking, the molecular dynamics simulation, and then enzyme kinetics assessment. The adopted screening procedure funnels out five novel inhibitors of NDM-1 including ZINC10936382, ZINC30479078, ZINC41493045, ZINC7424911, and ZINC84525623. The molecular mechanics-generalized born surface area and molecular dynamics (MD) simulation showed that ZINC84525623 formed the most stable complex with NDM-1. Furthermore, analyses of the binding pose after MD simulation revealed that ZINC84525623 formed two hydrogen bonds (electrostatic and hydrophobic interaction) with key amino acid residues of the NDM-1 active site. The docking binding free energy and docking binding constant for the ZINC84525623 and NDM-1 interaction were estimated to be −11.234 kcal/mol, and 1.74 × 108 M−1 respectively. Steady-state enzyme kinetics in the presence of ZINC84525623 show the decreased catalytic efficiency (i.e., kcat/Km) of NDM-1 on various antibiotics. The findings of this study would be helpful in identifying novel inhibitors against other β-lactamases from a pool of large databases. Furthermore, the identified inhibitor (ZINC84525623) could be developed as efficient drug candidates.

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Barone, Joseph V., Emma M. Tillman, and Robert J. Ferry. "Treatment of Transient Neonatal Diabetes Mellitus with Subcutaneous Insulin Glargine in an Extremely Low Birth Weight Neonate." Journal of Pediatric Pharmacology and Therapeutics 16, no. 4 (October 1, 2011): 291–97. http://dx.doi.org/10.5863/1551-6776-16.4.291.

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Neonatal diabetes mellitus (NDM) results from impaired insulin secretion. While rare, NDM presents complex challenges with regard to the management of glycemic control. NDM is classified as transient neonatal diabetes mellitus (TNDM) or permanent neonatal diabetes mellitus (PNDM). Determination of TNDM vs. PNDM is usually possible only after medical management has been initiated. Management of NDM begins with insulin; however, the correct dose, choice of formulation, and route of administration are complicated by the risk of neonatal hypoglycemia. For the first time, the successful management of TNDM in an extremely low birth weight (ELBW) neonate with the long-acting subcutaneous insulin analog, insulin glargine, is reported. In addition, potential pharmacokinetic barriers to treating ELBW neonates diagnosed with NDM with subcutaneous insulin products are discussed.

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Allander, Lisa, Karin Vickberg, Pernilla Lagerbäck, Linus Sandegren, and Thomas Tängdén. "Evaluation of In Vitro Activity of Double-Carbapenem Combinations against KPC-2-, OXA-48- and NDM-Producing Escherichia coli and Klebsiella pneumoniae." Antibiotics 11, no. 11 (November 17, 2022): 1646. http://dx.doi.org/10.3390/antibiotics11111646.

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Double-carbapenem combinations have shown synergistic potential against carbapenemase-producing Enterobacterales, but data remain inconclusive. This study evaluated the activity of double-carbapenem combinations against 51 clinical KPC-2-, OXA-48-, NDM-1, and NDM-5-producing Escherichia coli and Klebsiella pneumoniae and against constructed E. coli strains harboring genes encoding KPC-2, OXA-48, or NDM-1 in an otherwise isogenic background. Two-drug combinations of ertapenem, meropenem, and doripenem were evaluated in 24 h time-lapse microscopy experiments with a subsequent spot assay and in static time-kill experiments. An enhanced effect in time-lapse microscopy experiments at 24 h and synergy in the spot assay was detected with one or more combinations against 4/14 KPC-2-, 17/17 OXA-48-, 2/17 NDM-, and 1/3 NDM-1+OXA-48-producing clinical isolates. Synergy rates were higher against meropenem- and doripenem-susceptible isolates and against OXA-48 producers. NDM production was associated with significantly lower synergy rates in E. coli. In time-kill experiments with constructed KPC-2-, OXA-48- and NDM-1-producing E. coli, 24 h synergy was not observed; however, synergy at earlier time points was found against the KPC-2- and OXA-48-producing constructs. Our findings indicate that the benefit of double-carbapenem combinations against carbapenemase-producing E. coli and K. pneumoniae is limited, especially against isolates that are resistant to the constituent antibiotics and produce NDM.

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Cuzon, Gaelle, Rémy A. Bonnin, and Patrice Nordmann. "First Identification of Novel NDM Carbapenemase, NDM-7, in Escherichia coli in France." PLoS ONE 8, no. 4 (April 12, 2013): e61322. http://dx.doi.org/10.1371/journal.pone.0061322.

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Journal articles on the topic 'NDM'

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