Статті в журналах: "QacA"

1

Bayer, A. S., L. I. Kupferwasser, M. H. Brown, R. A. Skurray, S. Grkovic, T. Jones, K. Mukhopadhay, and M. R. Yeaman. "Low-Level Resistance of Staphylococcus aureus to Thrombin-Induced Platelet Microbicidal Protein 1 In Vitro Associated with qacA Gene Carriage Is Independent of Multidrug Efflux Pump Activity." Antimicrobial Agents and Chemotherapy 50, no. 7 (July 2006): 2448–54. http://dx.doi.org/10.1128/aac.00028-06.

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ABSTRACT Thrombin-induced platelet microbial protein 1 (tPMP-1), a cationic antimicrobial polypeptide released from thrombin-stimulated rabbit platelets, targets the Staphylococcus aureus cytoplasmic membrane to initiate its microbicidal effects. In vitro resistance to tPMP-1 correlates with survival advantages in vivo. In S. aureus, the plasmid-carried qacA gene encodes a multidrug transporter, conferring resistance to organic cations (e.g., ethidium [Et]) via proton motive force (PMF)-energized export. We previously showed that qacA also confers a tPMP-1-resistant (tPMP-1r) phenotype in vitro. The current study evaluated whether (i) transporters encoded by the qacB and qacC multidrug resistance genes also confer tPMP-1r and (ii) tPMP-1r mediated by qacA is dependent on efflux pump activity. In contrast to tPMP-1r qacA-bearing strains, the parental strain and its isogenic qacB- and qacC-containing strains were tPMP-1 susceptible (tPMP-1s). Efflux pump inhibition by cyanide m-chlorophenylhydrazone abrogated Etr, but not tPMP-1r, in the qacA-bearing strain. In synergy assays, exposure of the qacA-bearing strain to tPMP-1 did not affect the susceptibility of Et (ruling out Et-tPMP-1 cotransport). The following cytoplasmic membrane parameters did not differ significantly between the qacA-bearing and parental strains: contents of the major phospholipids; asymmetric distributions of the positively charged species, lysyl-phosphotidylglycerol; fatty acid composition; and relative surface charge. Of note, the qacA-bearing strain exhibited greater membrane fluidity than that of the parental, qacB-, or qacC-bearing strain. In conclusion, among these families of efflux pumps, only the multidrug transporter encoded by qacA conferred a tPMP-1r phenotype. These data suggest that qacA-encoded tPMP-1r results from the impact of a specific transporter upon membrane structure or function unrelated to PMF-dependent peptide efflux.

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2

Kawai, Mako, Sakuo Yamada, Ai Ishidoshiro, Yoshihiro Oyamada, Hideaki Ito, and Jun-ichi Yamagishi. "Cell-wall thickness: possible mechanism of acriflavine resistance in meticillin-resistant Staphylococcus aureus." Journal of Medical Microbiology 58, no. 3 (March 1, 2009): 331–36. http://dx.doi.org/10.1099/jmm.0.004184-0.

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Acriflavine resistance in the clinical meticillin-resistant Staphylococcus aureus isolate KT24 was found not to be mediated by multidrug efflux pumps encoded by qacA/B, smr, qacE, qacG, qacH, qacJ or norA. Early uptake and accumulation of ethidium bromide in MRSA KT24 was significantly lower than that in a susceptible strain, although the efflux rates were similar. Therefore, a permeability barrier in MRSA KT24 may be the conceivable mechanism of acriflavine resistance. Interestingly, it was found that MRSA KT24 had a significantly thickened cell wall, and that cell-wall thickness increased gradually during bacterial growth. In contrast, cell size and surface area in MRSA KT24 were not different from those in the susceptible strain. Moreover, MRSA KT24 exposure to sub-MIC concentrations of acriflavine resulted in a thicker cell wall. These results indicate that cell-wall thickness may be responsible for acriflavine resistance in S. aureus.

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3

He, Gui-Xin, Michael Landry, Huizhong Chen, Conner Thorpe, Dennis Walsh, Manuel F. Varela, and Hongmiao Pan. "Detection of benzalkonium chloride resistance in community environmental isolates of staphylococci." Journal of Medical Microbiology 63, no. 5 (May 1, 2014): 735–41. http://dx.doi.org/10.1099/jmm.0.073072-0.

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We isolated a total of 653 strains from 64 community environmental samples in Massachusetts, USA. Among these isolates, 9.65 % (63 strains) were benzalkonium chloride (BC)-resistant staphylococci. All BC-resistant strains were collected from surfaces upon which antibacterial wipes or antibacterial sprays containing 0.02–0.12 % BC had frequently been used in the fitness centres. However, isolates from surfaces upon which antibacterial wipes or antibacterial sprays had not been used were all sensitive to BC. All BC-resistant strains were also resistant to erythromycin, penicillin and ampicillin. In addition, 51 strains showed resistance to cetyltrimethylammonium bromide (CTAB), 15 strains showed resistance to chloramphenicol, 12 strains showed resistance to ciprofloxacin and four strains showed resistance to meticillin. Resistance gene analysis demonstrated that 41 strains contained qacA/B, 30 strains had qacC, 25 strains contained qacG, 16 strains had qacH and eight strains contained qacJ. These data indicate that application of BC is associated with environmental staphylococcal antimicrobial resistance.

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4

Nakaminami, Hidemasa, Norihisa Noguchi, and Masanori Sasatsu. "Fluoroquinolone Efflux by the Plasmid-Mediated Multidrug Efflux Pump QacB Variant QacBIII in Staphylococcus aureus." Antimicrobial Agents and Chemotherapy 54, no. 10 (July 26, 2010): 4107–11. http://dx.doi.org/10.1128/aac.01065-09.

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ABSTRACT Plasmids that carry the multidrug efflux genes qacA and qacB are widely distributed in methicillin-resistant Staphylococcus aureus (MRSA). Although the QacA and QacB proteins are similar to each other, their respective substrate specificities may differ. We investigated the variability and structure-function relationships of QacA and QacB in MRSA isolates. The amino acid sequences of 7 QacA and 25 QacB proteins showed that QacB was present in three variants, designated QacBII, QacBIII, and QacBIV, that were different from the prototypic QacB variant encoded by plasmid pSK23, which was named QacBI, while QacA was present in two variants. When cloned and expressed in S. aureus, the strain carrying qacBIII exhibited higher susceptibility to dyes and decreased susceptibility to norfloxacin and ciprofloxacin compared to strains carrying the other QacB variants. Site-directed mutagenesis experiments revealed that the residue at position 320 in QacB plays an important role in the resistance phenotypes to dyes and fluoroquinolones. Furthermore, the accumulation of norfloxacin and ciprofloxacin in the strain carrying qacBIII was significantly decreased. Our data demonstrate that the plasmid-mediated multidrug efflux pump QacB variant QacBIII confers the capability for fluoroquinolone efflux on S. aureus.

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5

Bjorland, Jostein, Terje Steinum, Marianne Sunde, Steinar Waage, and Even Heir. "Novel Plasmid-Borne Gene qacJ Mediates Resistance to Quaternary Ammonium Compounds in Equine Staphylococcus aureus, Staphylococcus simulans, and Staphylococcus intermedius." Antimicrobial Agents and Chemotherapy 47, no. 10 (October 2003): 3046–52. http://dx.doi.org/10.1128/aac.47.10.3046-3052.2003.

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ABSTRACT We identified a novel plasmid-borne gene (designated qacJ) encoding resistance to quaternary ammonium compounds (QACs) in three staphylococcal species associated with chronic infections in four horses. qacJ was located on a 2,650-bp plasmid (designated pNVH01), a new member of the pC194 family of rolling-circle replication plasmids. The 107-amino-acid protein, QacJ, showed similarities to known proteins of the small multidrug resistance family: Smr/QacC (72.5%), QacG (82.6%), and QacH (73.4%). The benzalkonium chloride MIC for a qacJ-containing recombinant was higher than those for otherwise isogenic recombinants expressing Smr, QacG, or QacH. Molecular epidemiological analyses by pulsed-field gel electrophoresis suggested both the clonal spread of a qacJ-harboring Staphylococcus aureus strain and the horizontal transfer of pNVH01 within and between different equine staphylococcal species. The presence of pNVH01 of identical nucleotide sequence in different staphylococcal species suggests that recent transfer has occurred. In three of the horses, a skin preparation containing cetyltrimethylammonium bromide had been used extensively for several years; this might explain the selection of staphylococci harboring the novel QAC resistance gene.

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6

Ergun, Y., Z. Cantekin, K. Gurturk, H. Solmaz, IH Ekin, and D. Ozturk. "Distribution of antiseptic resistance genes in Staphylococcus spp. from bovine mastitis." Veterinární Medicína 62, No. 4 (April 10, 2017): 200–203. http://dx.doi.org/10.17221/265/2015-vetmed.

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The purpose of this study was the determination of antiseptic resistance genes (qacA/B and qacC) from staphylococcal mastitis in cattle in various regions of Turkey. In total, 283 isolates (Burdur: 36, Hatay: 47 and Van: 200) were studied, and the antiseptic resistance genes were detected using simplex PCR. The distribution of the qacA/B and qacC genes, mediating resistance against quaternary ammonium compounds, was found to vary among the different isolates. The qacA/B genes were found in three of the Burdur isolates, six of the Hatay isolates and seven of the Van isolates. The qacC gene was found in two of the Burdur isolates, none of the Hatay isolates and two of the Van isolates. The presence of these genes and transmission among Staphylococcus spp. strains may pose risks in the control of mastitis, as well as to public health.

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7

Et al., Saber. "Detection a New Antiseptic Resistant Variant of qac Gene in Some Multi Drug Resistant Staphylococcus aureus Isolated from Different Clinical Sources." Baghdad Science Journal 16, no. 3 (September 1, 2019): 0571. http://dx.doi.org/10.21123/bsj.2019.16.3.0571.

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The increasing use of antiseptic compounds creates selective pressure cause emergence of antiseptic resistance among Staphylococcus aureus .Resistance mechanism of antiseptic is driven mainly by multi drug resistant (MDR) efflux protein.Sixty five isolates of S.aureuswere collected from different clinical sources and subjected to 11 antibiotics most of them are recognized by efflux systems as extruded substrates. Range of efflux activity was estimated using cartwheel method. Simultaneous discrimination of antiseptic coding genes (qacA/B, smr and norA)as well as nuc and mecA genes among multidrug resistantS.aureus(MRSA) isolates was preformed using multiplex PCR assay , 61 isolatesamong 65 were positive tonucand mecA genes, 58 of them were positive to norA, 14 of them were positive to qacA/B and only two were positive to smr. All isolates detected with qacA/B characterized by fluoroquinolones resistant and most of them show strong efflux activity at cartwheel assay, all of the 14 isolates positive qacA/B were sequenced to differentiate between variants depending on position 323 (aspartic in QacA, alanine in QacB), 3 of them harbored asparagines amino acid at position 323 and considered to be a new variants that reported for the first time.

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8

Paulsen, Ian T., Melissa H. Brown, and Ronald A. Skurray. "Characterization of the Earliest KnownStaphylococcus aureus Plasmid Encoding a Multidrug Efflux System." Journal of Bacteriology 180, no. 13 (July 1, 1998): 3477–79. http://dx.doi.org/10.1128/jb.180.13.3477-3479.1998.

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ABSTRACT The staphylococcal qacB-encoding multidrug resistance plasmid pSK156, isolated from a clinical strain dating from 1951, was characterized. Comparison of the regions flanking qacB with other qacA- and qacB-encoding plasmids provided insights into the evolution and dissemination of these multidrug efflux genes and led to the detection of the earliest known copy of the insertion sequence IS257.

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9

Sidhu, Maan Singh, Even Heir, Truls Leegaard, Karianne Wiger та Askild Holck. "Frequency of Disinfectant Resistance Genes and Genetic Linkage with β-Lactamase Transposon Tn552 among Clinical Staphylococci". Antimicrobial Agents and Chemotherapy 46, № 9 (вересень 2002): 2797–803. http://dx.doi.org/10.1128/aac.46.9.2797-2803.2002.

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ABSTRACT A total of 61 strains of Staphylococcus aureus and 177 coagulase-negative staphylococcal strains were isolated from the blood of patients with bloodstream infections and from the skin of both children under cancer treatment and human immunodeficiency virus-positive patients. The MIC analyses revealed that 118 isolates (50%) were resistant to quaternary ammonium compound-based disinfectant benzalkonium chloride (BC). The frequencies of resistance to a range of antibiotics were significantly higher among BC-resistant staphylococci than among BC-sensitive staphylococci. Of 78 BC-resistant staphylococcal isolates, plasmid DNA from 65 (83%), 2 (3%), 43 (55%), and 15 (19%) isolates hybridized to qacA or -B (qacA/B), qacC, blaZ, and tetK probes, respectively. The qacA/B and blaZ probes hybridized to the same plasmid in 19 (24%) staphylococcal strains. The plasmids harboring both qacA/B and blaZ genes varied from approximately 20 to 40 kb. The Staphylococcus epidermidis Fol62 isolate, harboring multiresistance plasmid pMS62, contained qacA/B and blaZ together with tetK. Molecular and genetic studies indicated different structural arrangements of blaZ and qacA/B, including variable intergenic distances and transcriptional directions of the two genes on the same plasmid within the strains. The different organizations may be due to the presence of various genetic elements involved in cointegration, recombination, and rearrangements. These results indicate that qac resistance genes are common and that linkage between resistance to disinfectants and penicillin resistance occurs frequently in clinical isolates in Norway. Moreover, the higher frequency of antibiotic resistance among BC-resistant strains indicates that the presence of either resistance determinant selects for the other during antimicrobial therapy and disinfection in hospitals.

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10

Kiley, John L., Dana M. Blyth, Dana M. Blyth, Miriam Beckius, Susan Kaiser, M. Leigh Carson, Dan Lu, et al. "543. Biocide Resistance Genes in Klebsiella spp. Infections from Trauma Patients in Iraq and Afghanistan." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S259. http://dx.doi.org/10.1093/ofid/ofz360.612.

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Abstract Background Biocides play an integral role in infection control. Paralleling concern about rising incidence of multidrug-resistant (MDR) organisms is a concern for resistance to biocides. In small studies, several genes involved in the production of efflux pump proteins have been identified as markers of biocide resistance in Klebsiella spp., namely cepA, qacA, qacE, qac∆E, and acrA. This study aimed to analyze the Klebsiella spp. isolates of a previously defined military trauma group with a high incidence of MDR organisms for the presence of these genes and their correlation with other resistance. Methods All infecting K. pneumoniae, K. variicola, and K. quasipneumoniae isolates archived by the Trauma Infectious Disease Outcomes Study (June 2009–December 2014) were selected. Additionally, all colonizing isolates linked with infecting isolates were included; the remainder to total 50 MDR and 46 non-MDR colonizing isolates were chosen randomly. Antimicrobial identification and susceptibilities were determined by CLSI criteria using the BD Phoenix Automated Microbiology System. PCR according to published methods for cepA, qacA, qacE, qac∆E, and acrA was accomplished in duplicate. MDR was defined as either resistance to ≥3 classes of aminoglycosides, β-lactams, carbapenems and/or fluoroquinolones or production of an ESBL or KPC. Results A total of 237 isolates (221 K. pneumoniae, 10 K. variicola, 6 K. quasipneumoniae) met inclusion criteria, of which 149 (63%) were MDR. All isolates had been exposed to antimicrobials prior to isolation. Of all isolates, 234 (98%) carried cepA: 218 (98%) K. pneumoniae carried cepA, 10 (100%) K. variicola carried cepA, and 6 (100%) of K. quasipneumoniae carried cepA. In addition, 148 (62%) isolates with cepA were MDR. One (10%) K. variicola isolate carried qacE along with cepA. This isolate was the only MDR K. variicola. None of the isolates carried qacA, qac∆E, or acrA. Conclusion We confirmed the near universal presence of the cepA biocide resistance gene in Klebsiella spp. isolated from trauma patients in Iraq and Afghanistan. In the largest evaluation of biocide resistance genes in Klebsiella spp. to our knowledge, the presence of qacA, qacE, qac∆E, and acrA was less common than has been reported elsewhere. Disclosures All authors: No reported disclosures.

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11

Hayden, Mary K., Karen Lolans, Katherine Haffenreffer, Taliser R. Avery, Ken Kleinman, Haiying Li, Rebecca E. Kaganov, et al. "Chlorhexidine and Mupirocin Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolates in the REDUCE-MRSA Trial." Journal of Clinical Microbiology 54, no. 11 (August 24, 2016): 2735–42. http://dx.doi.org/10.1128/jcm.01444-16.

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Whether targeted or universal decolonization strategies for the control of methicillin-resistant Staphylococcus aureus (MRSA) select for resistance to decolonizing agents is unresolved. The REDUCE-MRSA trial (ClinicalTrials registration no. NCT00980980) provided an opportunity to investigate this question. REDUCE-MRSA was a 3-arm, cluster-randomized trial of either screening and isolation without decolonization, targeted decolonization with chlorhexidine and mupirocin, or universal decolonization without screening to prevent MRSA infection in intensive-care unit (ICU) patients. Isolates from the baseline and intervention periods were collected and tested for susceptibility to chlorhexidine gluconate (CHG) by microtiter dilution; mupirocin susceptibility was tested by Etest. The presence of the qacA or qacB gene was determined by PCR and DNA sequence analysis. A total of 3,173 isolates were analyzed; 2 were nonsusceptible to CHG (MICs, 8 μg/ml), and 5/814 (0.6%) carried qacA or qacB . At baseline, 7.1% of MRSA isolates expressed low-level mupirocin resistance, and 7.5% expressed high-level mupirocin resistance. In a mixed-effects generalized logistic regression model, the odds of mupirocin resistance among clinical MRSA isolates or MRSA isolates acquired in an ICU in intervention versus baseline periods did not differ across arms, although estimates were imprecise due to small numbers. Reduced susceptibility to chlorhexidine and carriage of qacA or qacB were rare among MRSA isolates in the REDUCE-MRSA trial. The odds of mupirocin resistance were no different in the intervention versus baseline periods across arms, but the confidence limits were broad, and the results should be interpreted with caution.

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12

Lin, Kai-Hsiang, Chien-Yu Lin, Chieh-Chen Huang, Yu-Ling Ho, Shu-Fen Yang, and Cheng-Mao Ho. "Differentiation of qacA and qacB using high-resolution melt curve analysis, and both qacA and qacB but not qacC or norA types increase chlorhexidine minimal inhibitory concentrations in Staphylococcus aureus isolates." Journal of Microbiology, Immunology and Infection 53, no. 6 (December 2020): 900–908. http://dx.doi.org/10.1016/j.jmii.2020.09.006.

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13

Oliveira-Tintino, Cícera Datiane de Morais, Saulo Relison Tintino, Ana Carolina Justino de Araújo, Cristina Rodrigues dos Santos Barbosa, Priscilla Ramos Freitas, José Bezerra de Araújo Neto, Iêda Maria Begnini та ін. "Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains". Molecules 28, № 4 (15 лютого 2023): 1819. http://dx.doi.org/10.3390/molecules28041819.

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The bacterial species Staphylococcus aureus presents a variety of resistance mechanisms, among which the expression of β-lactamases and efflux pumps stand out for providing a significant degree of resistance to clinically relevant antibiotics. The 1,8-naphthyridines are nitrogen heterocycles with a broad spectrum of biological activities and, as such, are promising research targets. However, the potential roles of these compounds on bacterial resistance management remain to be better investigated. Therefore, the present study evaluated the antibacterial activity of 1,8-naphthyridine sulfonamides, addressing their ability to act as inhibitors of β-lactamases and efflux pump (QacA/B and QacC) against the strains SA-K4414 and SA-K4100 of S. aureus. All substances were prepared at an initial concentration of 1024 μg/mL, and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. Subsequently, their effects on β-lactamase- and efflux pump-mediated antibiotic resistance was evaluated from the reduction of the MIC of ethidium bromide (EtBr) and β-lactam antibiotics, respectively. The 1,8-naphthyridines did not present direct antibacterial activity against the strains SA-K4414 and SA-K4100 of S. aureus. On the other hand, when associated with antibiotics against both strains, the compounds reduced the MIC of EtBr and β-lactam antibiotics, suggesting that they may act by inhibiting β-lactamases and efflux pumps such as QacC and QacA/B. However, further research is required to elucidate the molecular mechanisms underlying these observed effects.

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14

Warren, David K., Martin Prager, Satish Munigala, Meghan A. Wallace, Colleen R. Kennedy, Kerry M. Bommarito, John E. Mazuski, and Carey-Ann D. Burnham. "Prevalence of qacA/B Genes and Mupirocin Resistance Among Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates in the Setting of Chlorhexidine Bathing Without Mupirocin." Infection Control & Hospital Epidemiology 37, no. 5 (February 2, 2016): 590–97. http://dx.doi.org/10.1017/ice.2016.1.

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OBJECTIVEWe aimed to determine the frequency of qacA/B chlorhexidine tolerance genes and high-level mupirocin resistance among MRSA isolates before and after the introduction of a chlorhexidine (CHG) daily bathing intervention in a surgical intensive care unit (SICU).DESIGNRetrospective cohort study (2005–2012)SETTINGA large tertiary-care centerPATIENTSPatients admitted to SICU who had MRSA surveillance cultures of the anterior naresMETHODSA random sample of banked MRSA anterior nares isolates recovered during (2005) and after (2006–2012) implementation of a daily CHG bathing protocol was examined for qacA/B genes and high-level mupirocin resistance. Staphylococcal cassette chromosome mec (SCCmec) typing was also performed.RESULTSOf the 504 randomly selected isolates (63 per year), 36 (7.1%) were qacA/B positive (+) and 35 (6.9%) were mupirocin resistant. Of these, 184 (36.5%) isolates were SCCmec type IV. There was a significant trend for increasing qacA/B (P=.02; highest prevalence, 16.9% in 2009 and 2010) and SCCmec type IV (P<.001; highest prevalence, 52.4% in 2012) during the study period. qacA/B(+) MRSA isolates were more likely to be mupirocin resistant (9 of 36 [25%] qacA/B(+) vs 26 of 468 [5.6%] qacA/B(−); P=.003).CONCLUSIONSA long-term, daily CHG bathing protocol was associated with a change in the frequency of qacA/B genes in MRSA isolates recovered from the anterior nares over an 8-year period. This change in the frequency of qacA/B genes is most likely due to patients in those years being exposed in prior admissions. Future studies need to further evaluate the implications of universal CHG daily bathing on MRSA qacA/B genes among hospitalized patients.Infect Control Hosp Epidemiol 2016;37:590–597

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Hang, Nguyen Thi, Vu Duc Hanh, Dam Van Phai, Lai Thi Lan Huong, Nguyen Thi Phuong, Le Van Truong, Mohsen Chitsaz, and Melissa H. Brown. "Successful Application of Site-directed Mutagenesis Polymerase Chain Reaction to Mutate TMS 11 of the Staphylococcal Multidrug Efflux Protein QacA." Vietnam Journal of Agricultural Sciences 3, no. 1 (August 12, 2020): 512–19. http://dx.doi.org/10.31817/vjas.2020.3.1.04.

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Staphylococcus aureus is a major problem in both the clinical setting and within the community. S. aureus can quickly develop resistance to a wide range of antibiotics through a number of different mechanisms, of which, using transporters located in the cell membrane to pump antibiotics out of the cell is the most serious concern. In staphylococcal species, QacA, one such important transporter, is encoded by qacA. QacA is 55kD in size and has 14 transmembrane segments (TMS) (TMS 1-TMS 14). This research describes the mutation process of the amino acid residues in TMS 11 of QacA using site-direct PCR. In this research, 15 primers were successfully designed for site-directed mutagenesis PCR. The site-mutagenesis PCR was successfully conducted to create 15 qacA mutants. These mutants will be used in further functional research of QacA.

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Takeuchi, Koh, Misaki Imai, and Ichio Shimada. "Conformational equilibrium defines the variable induction of the multidrug-binding transcriptional repressor QacR." Proceedings of the National Academy of Sciences 116, no. 40 (September 16, 2019): 19963–72. http://dx.doi.org/10.1073/pnas.1906129116.

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QacR, a multidrug-binding transcriptional repressor in pathogenic bacteria Staphylococcus aureus, modulates the transcriptional level of the multidrug transporter gene, qacA, in response to engaging a set of diverse ligands. However, the structural basis that defines the variable induction level remains unknown. Here, we reveal that the conformational equilibrium between the repressive and inducive conformations in QacR defines the induction level of the transporter gene. In addition, the unligated QacR is already partly populated in the inducive conformation, allowing the basal expression of the transporter. We also showed that, in the known constitutively active QacR mutants, the equilibrium is shifted more toward the inducive conformation, even in the unligated state. These results highlight the unexpected structural mechanism, connecting the promiscuous multidrug binding to the variable transcriptional regulation of QacR, which provide clues to dysfunctioning of the multidrug resistance systems.

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Nor A'shimi, Muhammad Harith, Ahmed Ghazi Alattraqchi, Farahiyah Mohd Rani, Nor Iza A Rahman, Salwani Ismail, Fatimah Haslina Abdullah, Norlela Othman, David W. Cleary, Stuart C. Clarke, and Chew Chieng Yeo. "Biocide susceptibilities and biofilm-forming capacities of Acinetobacter baumannii clinical isolates from Malaysia." Journal of Infection in Developing Countries 13, no. 07 (July 31, 2019): 626–33. http://dx.doi.org/10.3855/jidc.11455.

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Introduction. Acinetobacter baumannii is a Gram-negative nosocomial pathogen that has the capacity to develop resistance to all classes of antimicrobial compounds. However, very little is known regarding its susceptibility to biocides (antiseptics and disinfectants) and capacity to form biofilms, particularly for Malaysian isolates. Aim. To determine the susceptibility of A. baumannii isolates to commonly-used biocides, investigate their biofilm-forming capacities and the prevalence of biocide resistance and biofilm-associated genes. Methodology. The minimum inhibitory concentration (MIC) values of 100 A. baumannii hospital isolates from Terengganu, Malaysia, towards the biocides benzalkonium chloride (BZK), benzethonium chloride (BZT) and chlorhexidine digluconate (CLX), were determined by broth microdilution. The isolates were also examined for their ability to form biofilms in 96-well microplates. The prevalence of biocide resistance genes qacA, qacE and qacDE1 and the biofilm-associated genes bap and abaI were determined by polymerase chain reaction (PCR). Results. Majority of the A. baumannii isolates (43%) showed higher MIC values (> 50 µg/mL) for CLX than for BZK (5% for MIC > 50 µg/mL) and BZT (9% for MIC > 50 µg/mL). The qacDE1 gene was predominant (63%) followed by qacE (28%) whereas no isolate was found harbouring qacA. All isolates were positive for the bap and abaI genes although the biofilm-forming capacity varied among the isolates. Conclusion. The Terengganu A. baumannii isolates showed higher prevalence of qacDE1 compared to qacE although no correlation was found with the biocides’ MIC values. No correlation was also observed between the isolates’ biofilm-forming capacity and the MIC values for the biocides.

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Hassan, Karl A., Talal Souhani, Ronald A. Skurray, and Melissa H. Brown. "Analysis of Tryptophan Residues in the Staphylococcal Multidrug Transporter QacA Reveals Long-Distance Functional Associations of Residues on Opposite Sides of the Membrane." Journal of Bacteriology 190, no. 7 (January 25, 2008): 2441–49. http://dx.doi.org/10.1128/jb.01864-07.

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ABSTRACT Tryptophan residues can possess a multitude of functions within a multidrug transport protein, e.g., mediating interactions with substrates or distal parts of the protein, or fulfilling a structural requirement, such as guiding the depth of membrane insertion. In this study, the nine tryptophan residues of the staphylococcal QacA multidrug efflux protein were individually mutated to alanine and phenylalanine, and the functional consequences of these changes were determined. Phenylalanine substitutions for each tryptophan residue were functionally tolerated. However, alanine modifications revealed an important functional role for three tryptophan residues, W58, W149, and W173, each of which is well conserved among QacA-related transport proteins in the major facilitator superfamily. The most functionally compromising mutation, an alanine substitution for W58, likely to be located at the extracellular interface of transmembrane segment 2, abolished all detectable QacA-mediated resistance and transport function. Second-site suppressor analyses identified several mutations that rescued the function of the W58A QacA mutant. Remarkably, all of these suppressor mutations were shown to be located in cytoplasmic loops between transmembrane helices 2 and 3 or 12 and 13, demonstrating novel functional associations between amino acid positions on opposite sides of the membrane and in distal N- and C-terminal regions of the QacA protein.

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A. A. Jawad and N. M. Utba. "ANTISEPTICS RESISTANCE GENES (QACA/B, SMR) DETECTION AND EXPRESSION IN STAPHYLOCOCCUS AUREUS." IRAQI JOURNAL OF AGRICULTURAL SCIENCES 54, no. 4 (August 29, 2023): 1147–54. http://dx.doi.org/10.36103/ijas.v54i4.1808.

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This study was aimed to investigate the resistance of S. aureus to different antiseptics.This research indicate that the resistance of S.aureus to antiseptics is due to possessing either the smr gene or the qacA/B genes that associated with decreased susceptibility to antiseptics there for this study amid to determine the frequencies of S. aureus chloroxylenol resistant isolates and the presence of the previous genes in these isolates as well as the effect of chloroxylenol on the expression of these genes.189 clinical isolates isolated from skin infections identified as S. aureus in Baghdad by microscopical and biochemical tests. The chloroxylenol resistance S. aureus isolates was identified and chloroxylenol MIC was evaluated for these isolates. Antiseptic resistance genes (qacA/B, smr) were detected by PCR method and the results reveled that 21(84%) out of 25 isolates harbored qacA/B gene. While the smr gene was not demonstrated in any isolates. Furthermore, the chloroxylenol had no effect on qacA/B gene expression in these isolates.

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20

McGann, Patrick, Yoon I. Kwak, Amy Summers, James F. Cummings, Paige E. Waterman, and Emil P. Lesho. "Detection of qacA/B in Clinical Isolates of Methicillin-Resistant Staphylococcus aureus from a Regional Healthcare Network in the Eastern United States." Infection Control & Hospital Epidemiology 32, no. 11 (November 2011): 1116–19. http://dx.doi.org/10.1086/662380.

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We describe the clinical, microbiologic, and molecular features of the first series of qacA/B-containing strains of methicillin-resistant Staphylococcus aureus from infected US patients. All qac-carrying strains were clonally diverse, and qacA strains exhibited increased tolerance to chlorhexidine as measured by minimum inhibitory concentrations, minimum bactericidal concentrations, and postexposure colony counts.

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21

Mayer, S. "Distribution of the antiseptic resistance genes qacA, qacB and qacC in 497 methicillin-resistant and -susceptible European isolates of Staphylococcus aureus." Journal of Antimicrobial Chemotherapy 47, no. 6 (June 1, 2001): 896–97. http://dx.doi.org/10.1093/jac/47.6.896.

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22

Mitchell, Bernadette A., Melissa H. Brown, and Ronald A. Skurray. "QacA Multidrug Efflux Pump fromStaphylococcus aureus: Comparative Analysis of Resistance to Diamidines, Biguanidines, and Guanylhydrazones." Antimicrobial Agents and Chemotherapy 42, no. 2 (February 1, 1998): 475–77. http://dx.doi.org/10.1128/aac.42.2.475.

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ABSTRACT The staphylococcal multidrug efflux pump QacA mediates resistance to a broad spectrum of monovalent and divalent antimicrobial cations. Resistance toward various classes of these compounds identified features of the substrate that may be important for interaction with QacA. Analysis of combinations of two substrates suggested that the same mechanism is used for the extrusion of different classes of compounds.

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23

Grkovic, Steve, Melissa H. Brown, Maria A. Schumacher, Richard G. Brennan, and Ronald A. Skurray. "The Staphylococcal QacR Multidrug Regulator Binds a Correctly Spaced Operator as a Pair of Dimers." Journal of Bacteriology 183, no. 24 (December 15, 2001): 7102–9. http://dx.doi.org/10.1128/jb.183.24.7102-7109.2001.

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ABSTRACT Expression of the Staphylococcus aureusplasmid-encoded QacA multidrug transporter is regulated by the divergently encoded QacR repressor protein. To circumvent the formation of disulfide-bonded degradation products, site-directed mutagenesis to replace the two cysteine residues in wild-type QacR was undertaken. Analysis of a resultant cysteineless QacR derivative indicated that it retained full DNA-binding activities in vivo and in vitro and continued to be fully proficient for the mediation of induction ofqacA expression in response to a range of structurally dissimilar multidrug transporter substrates. The cysteineless QacR protein was used in cross-linking and dynamic light-scattering experiments to show that its native form was a dimer, whereas gel filtration indicated that four QacR molecules bound per DNA operator site. The addition of inducing compounds led to the dissociation of the four operator-bound QacR molecules from the DNA as dimers. Binding of QacR dimers to DNA was found to be dependent on the correct spacing of the operator half-sites. A revised model proposed for the regulation ofqacA expression by QacR features the unusual characteristic of one dimer of the regulatory protein binding to each operator half-site by a process that does not appear to require the prior self-assembly of QacR into tetramers.

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24

Xia, Yue Hua, and Yue Guang Li. "An Improved Quantum Ant Colony Algorithm of Solving Nonlinear Equation Groups." Advanced Materials Research 1049-1050 (October 2014): 1363–66. http://dx.doi.org/10.4028/www.scientific.net/amr.1049-1050.1363.

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In this paper, according to the characteristics of nonlinear equations. A new algorithm, Quantum Ant Colony Algorithm (QACA) is proposed. The core is that Q-bit and quantum rotation gate adopted in QEA are introduced into ACS to represent and update the pheromone respectively, so it has better diversity and global search capacity. The experimental result demonstrates that QACA can get better solutions to nonlinear equations.

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25

Kupferwasser, Leon Iri, Ronald A. Skurray, Melissa H. Brown, Neville Firth, Michael R. Yeaman, and Arnold S. Bayer. "Plasmid-Mediated Resistance to Thrombin-Induced Platelet Microbicidal Protein in Staphylococci: Role of theqacA Locus." Antimicrobial Agents and Chemotherapy 43, no. 10 (October 1, 1999): 2395–99. http://dx.doi.org/10.1128/aac.43.10.2395.

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ABSTRACT Thrombin-induced platelet microbicidal protein 1 (tPMP-1) is a small, cationic peptide released from rabbit platelets following thrombin stimulation. In vitro resistance to this peptide among strains of Staphylococcus aureus correlates with the survival advantage of such strains at sites of endothelial damage in humans as well as in experimental endovascular infections. The mechanisms involved in the phenotypic resistance of S. aureus to tPMP-1 are not fully delineated. The plasmid-encoded staphylococcal gene qacA mediates multidrug resistance to multiple organic cations via a proton motive force-dependent efflux pump. We studied whether the qacA gene might also confer resistance to cationic tPMP-1. Staphylococcal plasmids encoding qacA were found to confer resistance to tPMP-1 in an otherwise susceptible parental strain. Deletions which removed the region containing theqacA gene in the S. aureus multiresistance plasmid pSK1 abolished tPMP-1 resistance. Resistance to tPMP-1 in theqacA-bearing strains was inoculum independent but peptide concentration dependent, with the level of resistance decreasing at higher peptide concentrations for a given inoculum. There was no apparent cross-resistance in qacA-bearing strains to other endogenous cationic antimicrobial peptides which are structurally distinct from tPMP-1, including human neutrophil defensin 1, protamine, or the staphylococcal lantibiotics pep5 and nisin. These data demonstrate that the staphylococcal multidrug resistance geneqacA also mediates in vitro resistance to cationic tPMP-1.

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Grkovic, Steve, Melissa H. Brown, Natalie J. Roberts, Ian T. Paulsen, and Ronald A. Skurray. "QacR Is a Repressor Protein That Regulates Expression of theStaphylococcus aureusMultidrug Efflux Pump QacA." Journal of Biological Chemistry 273, no. 29 (July 17, 1998): 18665–73. http://dx.doi.org/10.1074/jbc.273.29.18665.

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27

Gahongayire, Solange, Adamu Almustapha Aliero, Charles Drago Kato, and Alice Namatovu. "Prevalence and Detection of qac Genes from Disinfectant-Resistant Staphylococcus aureus Isolated from Salon Tools in Ishaka Town, Bushenyi District of Uganda." Canadian Journal of Infectious Diseases and Medical Microbiology 2020 (August 12, 2020): 1–9. http://dx.doi.org/10.1155/2020/1470915.

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Bacterial infections are on a rise with causal-resistant strains increasing the economic burden to both patients and healthcare providers. Salons are recently reported as one of the sources for transmission of such resistant bacterial strains. The current study aimed at the identification of the prevalent bacteria and characterization of quaternary ammonium compound (qac) genes from disinfectant-resistant S. aureus isolated from salon tools in Ishaka town, Bushenyi District of Uganda. A total of 125 swabs were collected from different salon tools (combs, brushes, scissors, clippers, and shaving machines), and prevalent bacteria were isolated using standard microbiological methods. Identification of isolated bacteria was done using standard phenotypic methods including analytical profile index (API). Susceptibility patterns of the isolated bacteria to disinfectant were determined using the agar well diffusion method. Quaternary ammonium compound (qac) genes (qacA/B and qacC) associated with disinfectant resistances were detected from disinfectant-resistant S. aureus using multiplex polymerase chain reaction (PCR) and Sanger sequencing methods. Of the 125 swab samples collected from salons, 78 (62.4%) were contaminated with different bacteria species. Among the salon tools, clippers had the highest contamination of 20 (80.0%), while shaving machines had the lowest contamination of 11 (44.0%). The most prevalent bacteria identified were Staphylococcus epidermidis (28.1%) followed by S. aureus (26.5%). Of all the disinfectants tested, the highest resistance was shown with sodium hypochlorite 1%. Out of the eight (8) disinfectant-resistant S. aureus analysed for qac genes, 2 (25%) isolates (STP6 and STP9) were found to be qacA/B positive, while 2 (25%) isolates (STP8 and STP9) were found to be qacC gene positive. This study has shown that bacterial contamination of salon tools is common, coupled with resistance to disinfectants with sodium hypochlorite resistance being more common. Furthermore, observed resistance was attributed to the presence of qac genes among S. aureus isolates. A search for qac genes for disinfectant resistance from other bacteria species is recommended.

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Allaion, Josisleine Recalde, Karina Ghougassian Barrionuevo, Maria Jose Grande Burgos, Antonio Gálvez, and Bernadette Dora Gombossy de Melo Franco. "Staphylococcus aureus from Minas Artisanal Cheeses: Biocide Tolerance, Antibiotic Resistance and Enterotoxin Genes." Applied Sciences 12, no. 3 (January 19, 2022): 1019. http://dx.doi.org/10.3390/app12031019.

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Staphylococcus aureus is a common contaminant in artisanal raw-milk cheeses. Tolerance of S. aureus to biocides is a threat to disinfection in the cheese production environment, while antibiotic resistance and enterotoxin production are additional health concerns. This study aimed to evaluate the tolerance of S. aureus isolated from Minas artisanal cheeses to the biocides benzalkonium chloride, hexadecylpyridinium chloride, cetrimide, triclosan, hexachlorophene, and chlorhexidine, and the simultaneous occurrence of genes coding for antibiotic resistance (mecA, aacA-aphD, and tetK), efflux pumps [qacA/B and smr (qacC/D)], and enterotoxins (sea, seb, sec, sed, see, seg, seh, sei, and sej). Among the tested isolates, 38.2% were resistant to at least one biocide, and 73.1% were positive for one or more antibiotic resistance gene. Most of the biocide-tolerant and antibiotic-resistant isolates harbored efflux pump genes, and were positive for at least one staphylococcal enterotoxin gene. The study highlights the need for correct hygiene monitoring programs to ensure the safety of these products.

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JIA, Bei, Ting-quan ZHOU, Ai-long HUANG, and Wen-xiang HUANG. "Role of TMS5: staphylococcal multidrug-efflux protein QacA." Chinese Medical Journal 121, no. 5 (March 2008): 409–13. http://dx.doi.org/10.1097/00029330-200803010-00008.

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30

Mitchell, Bernadette A., Ian T. Paulsen, Melissa H. Brown, and Ronald A. Skurray. "Bioenergetics of the Staphylococcal Multidrug Export Protein QacA." Journal of Biological Chemistry 274, no. 6 (February 5, 1999): 3541–48. http://dx.doi.org/10.1074/jbc.274.6.3541.

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31

ZHANG, M., M. O'DONONGHUE, and M. V. BOOST. "Characterization of staphylococci contaminating automated teller machines in Hong Kong." Epidemiology and Infection 140, no. 8 (October 19, 2011): 1366–71. http://dx.doi.org/10.1017/s095026881100207x.

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SUMMARYEnvironmental staphylococcal contamination was investigated by culture of 400 automated teller machines (ATMs). Isolates were characterized for antibiotic and antiseptic susceptibility, carriage of antiseptic resistance genes (QAC genes), and spa types. MRSA, which was similar to local clinical isolates, was present on two (0·5%) of the 62 (15·5%) ATMs that yielded Staphylococcus aureus. QAC genes were more common in coagulase-negative staphylococci (qacA/B 26·0%, smr 14%) than S. aureus (11·3% qacA/B, 1·6% smr). QAC-positive isolates had significantly higher minimum inhibitory concentrations/minimum bactericidal concentrations to benzalkonium chloride and chlorhexidine digluconate. QAC gene presence was significantly associated with methicillin and tetracycline resistance. Survival of staphylococci, including MRSA, on common access sites may be facilitated by low disinfectant concentrations, which select for disinfectant-tolerant strains, while co-selecting for antibiotic-resistance determinants. Disinfection procedures should be performed correctly to help prevent spread of resistant pathogens from reservoirs in the community.

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Hrovat, Katja, Jerneja Čremožnik Zupančič, Katja Seme, and Jerneja Ambrožič Avguštin. "QAC Resistance Genes in ESBL-Producing E. coli Isolated from Patients with Lower Respiratory Tract Infections in the Central Slovenia Region—A 21-Year Survey." Tropical Medicine and Infectious Disease 8, no. 5 (May 12, 2023): 273. http://dx.doi.org/10.3390/tropicalmed8050273.

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Biocidal products prevent the spread of pathogenic microorganisms, including extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC), which is one of the most alarming health problems worldwide. Quaternary ammonium compounds (QACs) are surface-active agents that interact with the cytoplasmic membrane and are widely used in hospitals and food processing environments. A collection of 577 ESBL-EC, isolated from lower respiratory tract (LRT) samples, was screened for QAC resistance genes oqxA; oqxB; qacEΔ1; qacE; qacF/H/I; qacG; sugE (p); emrE; mdfA; sugE (c); ydgE; ydgF; and for class 1, 2, and 3 integrons. The prevalence of chromosome-encoded genes ranged from 77 to 100%, while the prevalence of QAC resistance genes encoded on mobile genetic elements (MGEs) was relatively low (0–0.9%), with the exception of qacEΔ1 (54.6%). PCR screening detected the presence of class 1 integrons in 36.3% (n = 210) of isolates, which were positively correlated with qacEΔ1. More correlations between QAC resistance genes, integrons, sequence type group ST131, and β-lactamase genes were presented. The results of our study confirm the presence of QAC resistance genes and also class 1 integrons commonly found in multidrug-resistant clinical isolates and highlight the potential role of QAC resistance genes in the selection of ESBL-producing E. coli in hospitals.

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Johnson, Ryan C., Carey D. Schlett, Katrina Crawford, Jeffrey B. Lanier, D. Scott Merrell, and Michael W. Ellis. "Recurrent Methicillin-Resistant Staphylococcus aureus Cutaneous Abscesses and Selection of Reduced Chlorhexidine Susceptibility during Chlorhexidine Use." Journal of Clinical Microbiology 53, no. 11 (August 19, 2015): 3677–82. http://dx.doi.org/10.1128/jcm.01771-15.

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We describe the selection of reduced chlorhexidine susceptibility during chlorhexidine use in a patient with two episodes of cutaneous USA300 methicillin-resistantStaphylococcus aureusabscess. The second clinical isolate harbors a novel plasmid that encodes the QacA efflux pump. Greater use of chlorhexidine for disease prevention warrants surveillance for resistance.

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34

Yuanping Li, Ling Feng, and Tharam Dillon. "QACA: Quality Assured Context Acquisition in Context-Aware Computing." Journal of Convergence Information Technology 6, no. 1 (January 31, 2011): 94–107. http://dx.doi.org/10.4156/jcit.vol6.issue1.12.

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35

Hassan, Karl A., Ronald A. Skurray, and Melissa H. Brown. "Transmembrane Helix 12 of the Staphylococcus aureus Multidrug Transporter QacA Lines the Bivalent Cationic Drug Binding Pocket." Journal of Bacteriology 189, no. 24 (October 19, 2007): 9131–34. http://dx.doi.org/10.1128/jb.01492-07.

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ABSTRACT An acidic residue in transmembrane segment (TMS) 10 is important for recognition of bivalent cationic substrates by the QacA multidrug transporter. Remarkably, an acidic residue in TMS 12 compensated for the absence of such a residue in TMS 10, suggesting that TMS 12 is a component of the bivalent cation-binding region.

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36

Xia, Guoqing, Zhiwei Han, Bo Zhao, Caiyun Liu, and Xinwei Wang. "Global Path Planning for Unmanned Surface Vehicle Based on Improved Quantum Ant Colony Algorithm." Mathematical Problems in Engineering 2019 (April 24, 2019): 1–10. http://dx.doi.org/10.1155/2019/2902170.

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As a tool to monitor marine environments and to perform dangerous tasks instead of manned vessels, unmanned surface vehicles (USVs) have extensive applications. Because most path planning algorithms have difficulty meeting the mission requirements of USVs, the purpose of this study was to plan a global path with multiple objectives, such as path length, energy consumption, path smoothness, and path safety, for USV in marine environments. A global path planning algorithm based on an improved quantum ant colony algorithm (IQACA) is proposed. The improved quantum ant colony algorithm is an algorithm that benefits from the high efficiency of quantum computing and the optimization ability of the ant colony algorithm. The proposed algorithm can plan a path considering multiple objectives simultaneously. The simulation results show that the proposed algorithm’s obtained minimum was 2.1–6.5% lower than those of the quantum ant colony algorithm (QACA) and ant colony algorithm (ACA), and the number of iterations required to converge to the minimum was 11.2–24.5% lower than those of the QACA and ACA. In addition, the optimized path for the USV was obtained effectively and efficiently.

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37

Paulsen, I. T., M. H. Brown, T. G. Littlejohn, B. A. Mitchell, and R. A. Skurray. "Multidrug resistance proteins QacA and QacB from Staphylococcus aureus: membrane topology and identification of residues involved in substrate specificity." Proceedings of the National Academy of Sciences 93, no. 8 (April 16, 1996): 3630–35. http://dx.doi.org/10.1073/pnas.93.8.3630.

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38

JIA, Bei, Ting-quan ZHOU, Ai-long HUANG, and Wen-xiang HUANG. "Retraction: Role of helix 5: staphylococcal multidrug efflux protein QacA." Chinese Medical Journal 124, no. 23 (December 2011): 4104. http://dx.doi.org/10.1097/00029330-201112010-00050.

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39

Correa, J. E., A. De Paulis, S. Predari, D. O. Sordelli, and P. E. Jeric. "First report of qacG, qacH and qacJ genes in Staphylococcus haemolyticus human clinical isolates." Journal of Antimicrobial Chemotherapy 62, no. 5 (July 18, 2008): 956–60. http://dx.doi.org/10.1093/jac/dkn327.

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40

Betchen, Melanie, Holly M. Giovinco, Michael Curry, Jackson Luu, Henry Fraimow, Valerie J. Carabetta, and Raquel Nahra. "Evaluating the Effectiveness of Hospital Antiseptics on Multidrug-Resistant Acinetobacter baumannii: Understanding the Relationship between Microbicide and Antibiotic Resistance." Antibiotics 11, no. 5 (May 3, 2022): 614. http://dx.doi.org/10.3390/antibiotics11050614.

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Анотація:

Acinetobacter baumannii hospital infections are difficult to treat due to the rapid emergence of multidrug-resistant (MDR) strains. In addition, A. baumannii can survive in numerous adverse environments, including in the presence of common hospital antiseptics. We hypothesized that in addition to accumulating drug resistance determinants, MDR A. baumannii strains also accumulate mutations that allow for greater microbicide tolerance when compared to pan-susceptible (PS) strains. To test this hypothesis, we compared the survival of five MDR and five PS patient isolates when exposed to bleach, ethanol, quaternary ammonium compounds, chlorhexidine gluconate, and povidone. We evaluated bacteria in a free-living planktonic state and under biofilm conditions. Each disinfectant eliminated 99.9% of planktonic bacteria, but this was not the case for bacterial biofilms. Next, we characterized strains for the presence of the known microbicide-resistance genes cepA, qacEΔ1, qacE, and qacA. MDR strains did not survive more than PS strains in the presence of microbicides, but microbicide-resistant strains had higher survival rates under some conditions. Interestingly, the PS strains were more likely to possess microbicide-resistance genes. Microbicide resistance remains an important topic in healthcare and may be independent of antimicrobial resistance. Hospitals should consider stricter isolation precautions that take pan-susceptible strains into account.

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41

Abd El-Aziz, Norhan K., Ahmed M. Ammar, Hend M. El Damaty, Rehab A. Abd Elkader, Hosam A. Saad, Waleed El-Kazzaz, and Eman Khalifa. "Environmental Streptococcus uberis Associated with Clinical Mastitis in Dairy Cows: Virulence Traits, Antimicrobial and Biocide Resistance, and Epidemiological Typing." Animals 11, no. 7 (June 22, 2021): 1849. http://dx.doi.org/10.3390/ani11071849.

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Mastitis remains a serious problem for dairy animals. The misappropriation of antimicrobial agents helps accelerate resistance, which poses a serious challenge in controlling environmental S. uberis infection. Here, we study the virulence attributes, antimicrobial and biocide resistance, and epidemiological typing of S. uberis recovered from bovine clinical mastitis in dairy farms of diverse hygienic interventions in Egypt. The overall S. uberis infection rate was 20.59%; all were multidrug-resistant (MDR). The sua gene was the most frequent virulence gene (42.02%), followed by pauA (40.57%), cfu (21.73%), skc (20.28%), and opp (11.59%). The erm(B) gene served as the predominant antimicrobial-resistant gene (75.36%), followed by fexA (52.63%) and tet(M), blaZ, and aac(6′)aph(2″) genes (46.38% each). Of note, 79.71%, 78.26%, and 18.84% of S. uberis isolates harbored qacED1, qacC/D, and qacA/B genes, respectively. All analyzed isolates were S. uberis type I by their unique RFLP–PCR pattern. In conclusion, the sustained presence of pauA and sua genes throughout the investigated farms contributes to a better understanding of the bacterium’s pathogenicity. Furthermore, MDR coupled with the existence of biocide resistance genes indicates the importance of S. uberis surveillance and the prudent use of antimicrobials in veterinary clinical medicine to avoid the dissemination of antimicrobial resistance.

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Hassan, Karl A., Zhiqiang Xu, Ryan E. Watkins, Richard G. Brennan, Ronald A. Skurray, and Melissa H. Brown. "Optimized production and analysis of the staphylococcal multidrug efflux protein QacA." Protein Expression and Purification 64, no. 2 (April 2009): 118–24. http://dx.doi.org/10.1016/j.pep.2008.11.009.

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43

Anthonisen, I. L., M. Sunde, T. M. Steinum, M. S. Sidhu та H. Sørum. "Organization of the Antiseptic Resistance Gene qacA and Tn552-Related β-Lactamase Genes in Multidrug- Resistant Staphylococcus haemolyticus Strains of Animal and Human Origins". Antimicrobial Agents and Chemotherapy 46, № 11 (листопад 2002): 3606–12. http://dx.doi.org/10.1128/aac.46.11.3606-3612.2002.

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ABSTRACT A part (12 kb) of a plasmid containing the β-lactamase genes of Tn552, the disinfectant resistance gene qacA, and flanking DNA has been cloned from a Staphylococcus haemolyticus isolate and sequenced. This region was used to map the corresponding regions in six other multiresistant S. haemolyticus isolates of human and animal origin. The organizations of the genetic structures were almost identical in all isolates studied. The β-lactamase and qacA genes from S. haemolyticus have >99.9% identities at the nucleotide level with the same genes from S. aureus, demonstrating that various staphylococcal species able to colonize animal and human hosts can exchange the genetic elements involved in resistance to antibiotics and disinfectants. The use of antibiotics and disinfectants in veterinary practice and animal husbandry may also contribute to the selection and maintenance of resistance factors among the staphylococcal species. Different parts of the 12-kb section analyzed had high degrees of nucleotide identity with regions from several other different Staphylococcus aureus plasmids. This suggests the contribution of interplasmid recombination in the evolutionary makeup of this 12-kb section involving plasmids that can intermingle between various staphylococcal species. The lateral spread of resistance genes between various staphylococcal species is probably facilitated by the generation of large multiresistance plasmids and the subsequent interspecies exchange of them.

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44

Ho, Cheng-Mao, Chi-Yuan Li, Mao-Wang Ho, Chien-Yu Lin, Shu-Hui Liu, and Jang-Jih Lu. "High Rate ofqacA- andqacB-Positive Methicillin-Resistant Staphylococcus aureus Isolates from Chlorhexidine-Impregnated Catheter-Related Bloodstream Infections." Antimicrobial Agents and Chemotherapy 56, no. 11 (August 20, 2012): 5693–97. http://dx.doi.org/10.1128/aac.00761-12.

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ABSTRACTChlorhexidine has been widely used for infection control. Although the use of chlorhexidine-impregnated catheters has reduced catheter-related infections, chlorhexidine-resistantStaphylococcus aureushas emerged. The correlation between the existence of the chlorhexidine-resistant genesqacAandqacB(qacA/B) in methicillin-resistantStaphylococcus aureus(MRSA) isolates and the effectiveness of chlorhexidine-impregnated catheters in the prevention of MRSA infections is unknown. Sixty methicillin-sensitiveStaphylococcus aureus(MSSA) and 96 MRSA isolates from the blood cultures of different patients were collected, and a case-control study was conducted to determine whether more clinicalS. aureusisolates from chlorhexidine-impregnated catheter-related bloodstream infections (CRBSI) have the biocide-resistant genes (qacA/Borsmr) than those from other infections. The chlorhexidine MIC50s of MSSA and MRSA isolates were 1 μg/ml and 2 μg/ml, respectively. Results of PCR analyses showed that 3.3% (n= 2) of MSSA and 43.8% (n= 42) of MRSA isolates harboredqacA/Band 5% (n= 3) of MSSA and 25% (n= 24) of MRSA isolates containedsmr. With multivariate logistic regression analyses, the significant risk factors for definite CRBSI with chlorhexidine-impregnated catheters were determined to beS. aureusisolates withqacA/Band a chlorhexidine MIC of ≥2 μg/ml (odds ratios [OR], 9.264 and 8.137, respectively, in all 156S. aureusisolates and 6.097 and 4.373, respectively, in the 96 MRSA isolates). Further prospective studies are needed to investigate the transmission of these biocide-resistant genes.

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45

HORNER, C., L. UTSI, L. COOLE, and M. DENTON. "Epidemiology and microbiological characterization of clinical isolates of Staphylococcus aureus in a single healthcare region of the UK, 2015." Epidemiology and Infection 145, no. 2 (October 28, 2016): 386–96. http://dx.doi.org/10.1017/s0950268816002387.

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SUMMARYWe investigated the epidemiology and characterization of isolates of Staphylococcus aureus within the Yorkshire and Humber (YH) region in the UK. In July 2015, each laboratory within YH (n = 14) was assigned two consecutive days during which all clinical isolates of S. aureus were collected. Isolates were tested for antibiotic susceptibilities and the presence of genes encoding methicillin resistance (mecA and mecC), Panton–Valentine leukocidin (PVL) (lukS-PV), and efflux-mediated chlorhexidine resistance (qacA); isolates were also characterized by spa-types. Minimum inhibitory concentrations (MICs) to chlorhexidine were determined by the broth dilution method. Of 520 isolates collected, 6·2% were methicillin-resistant S. aureus (MRSA, all mecA-positive) and mupirocin resistance was low [0·8%, 95% confidence interval (CI) 0·3–2·0] and only found in MRSA. Carriage of the qacA gene was identified in 1·7% (95% CI 0·8–3·3) of isolates and 3·5% (95% CI 2·2–5·4) had a chlorhexidine MIC of 4 mg/l. The PVL gene was infrequent (3·7%, 95% CI 2·4–5·6). Genotyping identified 234 spa-types that mapped to 22 clonal complexes. Comparison of these current data with previous work suggest that the widespread use of staphylococcal decolonization regimens over the past decade or more has not had an adverse impact on resistance rates, PVL carriage or the prevalence of specific S. aureus lineages.

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46

Ye, H. F., M. Zhang, M. O’Donoghue, and M. Boost. "Are qacG, qacH and qacJ genes transferring from food isolates to carriage isolates of staphylococci?" Journal of Hospital Infection 80, no. 1 (January 2012): 95–96. http://dx.doi.org/10.1016/j.jhin.2011.08.024.

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47

Bardasheva, Alevtina, Artem Tikunov, Yuliya Kozlova, Elena Zhirakovskaia, Valeriya Fedorets, Natalya Fomenko, Tatyana Kalymbetova, et al. "Antibiotic Resistance and Pathogenomics of Staphylococci Circulating in Novosibirsk, Russia." Microorganisms 9, no. 12 (November 30, 2021): 2487. http://dx.doi.org/10.3390/microorganisms9122487.

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A total of 394 strains of staphylococci found in humans and pets in Novosibirsk, Siberian Russia, were characterized in terms of antibiotic resistance and corresponding genes. Two coagulase-positive and 17 coagulase-negative species were identified. The majority of isolates, with the exception of S. haemolyticus and hospital S. epidermidis isolates, were sensitive to most of the tested antibiotics, and isolates from pets displayed the lowest level of resistance. Nevertheless, methicillin-resistant (MRS) and/or multidrug-resistant (MDR) isolates were found in all prevailed species, including coagulase-negative. A set of genes corresponding to the detected resistance was identified: mecA (beta-lactam resistance), aac(6′)-Ie-aph(2″)-Ia, aph(3′)-IIIa, ant(4′)-Ia (aminoglycoside-modifying enzymes), ermA/ermC, and msrA (macrolide resistance). Complete genome analysis for ten MDR S. epidermidis and five MDR S. haemolyticus isolates revealed additional antibiotic resistance genes mphC, qacA/qacB, norA, dfrC/dfrG, lnuA, BseSR, and fosB. NorA, dfrC, and fosB were present in all S. epidermidis genomes, whereas mphC and msrA were identified in all S. haemolyticus ones. All investigated MDR S. epidermidis and four of five S. haemolyticus strains were moderate or strong biofilm producers, whereas multiple genes responsible for this function and for virulence and pathogenicity were identified mostly in S. epidermidis, but were less frequently represented in S. haemolyticus.

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48

Bonsaglia, Erika C. R., Gustavo H. Calvo, Daniel O. Sordelli, Nathalia C. C. Silva, Vera L. M. Rall, Adriana Casas, and Fernanda Buzzola. "The Impact of Low-Level Benzalkonium Chloride Exposure on Staphylococcus spp. Strains and Control by Photoinactivation." Antibiotics 12, no. 8 (July 28, 2023): 1244. http://dx.doi.org/10.3390/antibiotics12081244.

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Exposure of bacteria to low concentrations of biocides can facilitate horizontal gene transfer, which may lead to bacterial adaptive responses and resistance to antimicrobial agents. The emergence of antibacterial resistance not only poses a significant concern to the dairy industry but also adds to the complexity and cost of mastitis treatment. This study was aimed to evaluate how selective stress induced by benzalkonium chloride (BC) promotes antibiotic non-susceptibility in Staphylococcus spp. In addition, we investigated the efficacy of photodynamic inactivation (PDI) in both resistant and susceptible strains. The study determined the minimum inhibitory concentration (MIC) of BC using the broth microdilution method for different Staphylococcus strains. The experiments involved pairing strains carrying the qacA/qacC resistance genes with susceptible strains and exposing them to subinhibitory concentrations of BC for 72 h. The recovered isolates were tested for MIC BC and subjected to disc diffusion tests to assess changes in susceptibility patterns. The results demonstrated that subinhibitory concentrations of BC could select strains with reduced susceptibility and antibiotic resistance, particularly in the presence of S. pasteuri. The results of PDI mediated by toluidine blue (100 µM) followed by 60 min irradiation (total light dose of 2.5 J/cm2) were highly effective, showing complete inactivation for some bacterial strains and a reduction of up to 5 logs in others.

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Cheng, J., K. Baldwin, A. A. Guffanti, and T. A. Krulwich. "Na+/H+ antiport activity conferred by Bacillus subtilis tetA(L), a 5' truncation product of tetA(L), and related plasmid genes upon Escherichia coli." Antimicrobial Agents and Chemotherapy 40, no. 4 (April 1996): 852–57. http://dx.doi.org/10.1128/aac.40.4.852.

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An Escherichia coli transformant expressing the Bacillus subtilis tetA(L) gene from a weak promoter was challenged by growth on medium with low, increasing tetracycline concentrations. Changes in the substrate preference ratios of the TetA(L)-mediated resistances and antiports were examined in view of recent findings suggesting that TetA(L) catalyzes efflux of Na+ in exchange for protons in addition to having the ability to catalyze metal-tetracycline/H+ antiport. After growth of the transformant on 1 microgram or more of tetracycline per ml for 12 to 15 h, the tetA(L) gene in the plasmid was found to be disrupted by an IS10 element 50 bp from the 5' end of the coding sequence. This disrupted recombinant plasmid, pKB1, conferred greater tetracycline resistance and higher levels of membrane metal-tetracycline/proton antiport than the original plasmid, pJTA1, but conferred lower NA+ resistance and Na+/H+ antiport levels than the original plasmid. The results indicate that the 5' end of the gene is necessary for optimal Na+/H+ antiport but that some such activity as well as robust tetracycline/H+ antiport persists in its absence. Two plasmid genes, tet(K) and qacA, were compared with tetA(L) vis-à-vis their abilities to enhance the Na+/H+ antiporter activity of everted vesicles from E. coli transformants. tet(K), which is more closely related to tetA(L), catalyzed 22Na+ uptake by energized vesicles, whereas the less closely related qacA gene did not.

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Miyazaki, Neide H. Tokumaru, Alessandra O. Abreu, Victor A. Marin, Cleide AF Rezende, Márcia TB Moraes, and Maria Helena S. Villas Bôas. "The presence of qacA/B gene in Brazilian methicillin-resistant Staphylococcus aureus." Memórias do Instituto Oswaldo Cruz 102, no. 4 (June 2007): 539–40. http://dx.doi.org/10.1590/s0074-02762007000400018.

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