Remodeling of pSK1 Family Plasmids and Enhanced Chlorhexidine Tolerance in a Dominant Hospital Lineage of Methicillin-Resistant
            <i>Staphylococcus aureus</i>

Baines, Sarah L.; Jensen, Slade O.; Firth, Neville; Silva, Anders Gonçalves da; Seemann, Torsten; Carter, Glen P.; Williamson, Deborah A.; Howden, Benjamin P; Stinear, Timothy P.

doi:10.1128/aac.02356-18

Cited by 20 publications

(22 citation statements)

References 63 publications

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“…pGO1evol 2 and pGO1evol 3 also exhibited reduction via recombination between these sites. These data are consistent with others’ observations that IS elements facilitate distinct remodelling strategies for the evolution of medium-to-large composite plasmids 27 .…”

Section: Resultssupporting

confidence: 93%

Staphylococcal phages and pathogenicity islands drive plasmid evolution

et al. 2021

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Conjugation has classically been considered the main mechanism driving plasmid transfer in nature. Yet bacteria frequently carry so-called non-transmissible plasmids, raising questions about how these plasmids spread. Interestingly, the size of many mobilisable and non-transmissible plasmids coincides with the average size of phages (~40 kb) or that of a family of pathogenicity islands, the phage-inducible chromosomal islands (PICIs, ~11 kb). Here, we show that phages and PICIs from Staphylococcus aureus can mediate intra- and inter-species plasmid transfer via generalised transduction, potentially contributing to non-transmissible plasmid spread in nature. Further, staphylococcal PICIs enhance plasmid packaging efficiency, and phages and PICIs exert selective pressures on plasmids via the physical capacity of their capsids, explaining the bimodal size distribution observed for non-conjugative plasmids. Our results highlight that transducing agents (phages, PICIs) have important roles in bacterial plasmid evolution and, potentially, in antimicrobial resistance transmission.

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Section: Resultssupporting

confidence: 93%

Staphylococcal phages and pathogenicity islands drive plasmid evolution

et al. 2021

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“…Conversely, a strain with a lower plasmid copy number would produce less QacR, and thus qacA expression could be higher due to a decrease in the amount of the repressor. Intriguingly, this regulatory model also explains the increased resistance seen upon qacA and qacR integration into the chromosome (48); in a single copy, smaller amounts of functional QacR dimers would lead to increased expression of qacA and thus increased CHX resistance. Future targeted mechanistic studies will seek to investigate the proposed regulatory model.…”

Section: Discussionmentioning

confidence: 90%

“…For example, CHX is a well-tolerated antiseptic that has been shown to be effective as a presurgical skin preparation. Though prior thought suggested that antiseptic resistance was unlikely (7), the ubiquitous use of CHX in hospitals and the community has led to the appearance of strains of bacteria, including S. aureus, that are more resistant to CHX (9,48). Furthermore, the increasing presence of QACs such as BKC in everyday personalcare products appears to have provided an additional selection for efflux-mediated antiseptic resistance in bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…In all three of these genomes, the two genes are separated by Ͼ200 kb, suggesting that separate integration events are responsible for dual carriage. While the majority of S. aureus literature indicates that qacA typically resides on a plasmid (23), a recent publication from Australia described stable chromosomal integration of a qacA-positive plasmid in S. aureus clinical isolates (48). The integration event was linked to increased CHX tolerance and was hypothesized to result in a change in qacA expression.…”

Section: Discussionmentioning

confidence: 99%

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Systematic Analysis of Efflux Pump-Mediated Antiseptic Resistance in Staphylococcus aureus Suggests a Need for Greater Antiseptic Stewardship

LaBreck

Bochi-Layec

Stanbro

et al. 2020

mSphere

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Staphylococcus aureus-associated infections can be difficult to treat due to multidrug resistance. Thus, infection prevention is critical. Cationic antiseptics, such as chlorhexidine (CHX) and benzalkonium chloride (BKC), are liberally used in health care and community settings to prevent infection. However, increased administration of antiseptics has selected for S. aureus strains that show reduced susceptibilities to cationic antiseptics. This increased resistance has been associated with carriage of specific efflux pumps (QacA, QacC, and NorA). Since prior published studies focused on different strains and on strains carrying only a single efflux gene, the relative importance of these various systems to antiseptic resistance is difficult to ascertain. To overcome this, we engineered a collection of isogenic S. aureus strains that harbored norA, qacA, and qacC, individually or in combination. MIC assays showed that qacA was associated with increased resistance to CHX, cetrimide (CT), and BKC, qacC was associated with resistance to CT and BKC, and norA was necessary for basal-level resistance to the majority of tested antiseptics. When all three pumps were present in a single strain, an additive effect was observed in the MIC for CT. Transcriptional analysis revealed that expression of qacA and norA was significantly induced following exposure to BKC. Alarmingly, in a strain carrying qacA and norA, preexposure to BKC increased CHX tolerance. Overall, our results reveal increased antiseptic resistance in strains carrying multiple efflux pumps and indicate that preexposure to BKC, which is found in numerous daily-use products, can increase CHX tolerance. IMPORTANCE S. aureus remains a significant cause of disease within hospitals and communities. To reduce the burden of S. aureus infections, antiseptics are ubiquitously used in our daily lives. Furthermore, many antiseptic compounds are dual purpose and are found in household products. The increased abundance of antiseptic compounds has selected for S. aureus strains that carry efflux pumps that increase resistance to antiseptic compounds; however, the effect of carrying multiple pumps within S. aureus is unclear. We demonstrated that an isogenic strain carrying multiple efflux pumps had an additive resistance phenotype to cetrimide. Moreover, in a strain carrying qacA and norA, increased chlorhexidine tolerance was observed after the strain was preexposed to subinhibitory concentrations of a different common-use antiseptic. Taken together, our findings demonstrate cooperation between antiseptic resistance efflux pumps and suggest that their protective phenotype may be exacerbated by priming with subinhibitory concentrations of household antiseptics.

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“…The acquisition of these different genetic elements in a single large plasmid can enhance adaptation and dissemination of S. aureus in different environments due to co-selective advantage (Wall et al, 2016). A recent study investigating ST239 MRSA strains evolution over the last 32 years revealed that plasmids coevolved with strains and enhanced resistance to multiple antibiotics (Baines et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization of Staphylococcus aureus Plasmids Associated With Strains Isolated From Various Retail Meats

et al. 2020

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Staphylococcus aureus is considered one of the most important foodborne bacterial pathogens causing food poisoning and related illnesses. S. aureus strains harbor plasmids encoding genes for virulence and antimicrobial resistance, but few studies have investigated S. aureus plasmids, especially megaplasmids, in isolates from retail meats. Furthermore, knowledge about the distribution of genes encoding replication (rep) initiation proteins in food isolates is lacking. In this study, the prevalence of plasmids in S. aureus strains isolated from retail meats purchased in Oklahoma was investigated; furthermore, we evaluated associations between rep families, selected virulence and antimicrobial resistance genes, and food source origin. Two hundred and twenty-two S. aureus isolates from chicken (n = 55), beef liver (n = 43), pork (n = 42), chicken liver (n = 29), beef (n = 24), turkey (n = 22), and chicken gizzards (n = 7) were subjected to plasmid screening with alkaline lysis and PFGE to detect small-to-medium sized and large plasmids, respectively. The S. aureus isolates contained variable sizes of plasmids, and PFGE was superior to alkaline lysis in detecting large megaplasmids. A total of 26 rep families were identified by PCR, and the most dominant rep families were rep 10 and rep 7 in 164 isolates (89%), rep 21 in 124 isolates (56%), and rep 12 in 99 isolates (45%). Relationships between selected rep genes, antimicrobial resistance and virulence genes, and meat sources were detected. In conclusion, S. aureus strains isolated from retail meats harbor plasmids with various sizes and there is an association between rep genes on these plasmids and the meat source or the antimicrobial resistance of the strains harboring them.

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Remodeling of pSK1 Family Plasmids and Enhanced Chlorhexidine Tolerance in a Dominant Hospital Lineage of Methicillin-Resistant Staphylococcus aureus

Cited by 20 publications

References 63 publications

Staphylococcal phages and pathogenicity islands drive plasmid evolution

Staphylococcal phages and pathogenicity islands drive plasmid evolution

Systematic Analysis of Efflux Pump-Mediated Antiseptic Resistance in Staphylococcus aureus Suggests a Need for Greater Antiseptic Stewardship

Molecular Characterization of Staphylococcus aureus Plasmids Associated With Strains Isolated From Various Retail Meats

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