Conjugative Transfer of a Novel Staphylococcal Plasmid Encoding the Biocide Resistance Gene, qacA.

Patrick T Labreck,Eugene V Millar,Kimberly A Bishop-Lilly,Natasha N Law,Gregory K Rice,Emad M Elassal,Adrian C Paskey,Michael W Ellis,Carey D Schlett,D Scott Merrell,Theron Hamilton,Regina Z Cer,Jason W Bennett

doi:10.3389/fmicb.2018.02664

Abstract

Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTI). Some S. aureus strains harbor plasmids that carry genes that affect resistance to biocides. Among these genes, qacA encodes the QacA Multidrug Efflux Pump that imparts decreased susceptibility to chlorhexidine, a biocide used ubiquitously in healthcare facilities. Furthermore, chlorhexidine has been considered as a S. aureus decolonization strategy in community settings. We previously conducted a chlorhexidine-based SSTI prevention trial among Ft. Benning Army trainees. Analysis of a clinical isolate (C02) from that trial identified a novel qacA-positive plasmid, pC02. Prior characterization of qacA-containing plasmids is limited and conjugative transfer of those plasmids has not been demonstrated. Given the implications of increased biocide resistance, herein we characterized pC02. In silico analysis identified genes typically associated with conjugative plasmids. Moreover, pC02 was efficiently transferred to numerous S. aureus strains and to Staphylococcus epidermidis. We screened additional qacA-positive S. aureus clinical isolates and pC02 was present in 27% of those strains; other unique qacA-harboring plasmids were also identified. Ten strains were subjected to whole genome sequencing. Sequence analysis combined with plasmid screening studies suggest that qacA-containing strains are transmitted among military personnel at Ft. Benning and that strains carrying qacA are associated with SSTIs within this population. The identification of a novel mechanism of qacA conjugative transfer among Staphylococcal strains suggests a possible future increase in the prevalence of antiseptic tolerant bacterial strains, and an increase in the rate of infections in settings where these agents are commonly used.

Highlights

Community-Associated Methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are a significant issue in the United States, and it is estimated that they are responsible for 65% of all MRSA infections (Dukic et al, 2013)
There is a lack of genomic information available for CA-MRSA strains that carry qacA
To characterize both colonizing and clinically relevant qacA-positive S. aureus strains, we initially examined 11 qacA/B positive strains and 8 qacA/Bnegative control strains (Tables 1, 2) that were all obtained from a chlorhexidine-based soft tissue infections (SSTI) prevention trial (Ellis et al, 2014; Schlett et al, 2014); the previously characterized C01 and C02 strains (Johnson et al, 2015) were included for comparison (Table 1)

Summary

Introduction

Community-Associated Methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are a significant issue in the United States, and it is estimated that they are responsible for 65% of all MRSA infections (Dukic et al, 2013). Colonization of multiple body sites is known to occur (Albrecht et al, 2015; Singh et al, 2016), and colonization is a clear risk factor for S. aureus infection (Albrecht et al, 2015) Given these possibilities, decolonization of S. aureus has been employed as a disease prevention strategy (Buehlmann et al, 2008; Coates et al, 2009). Decolonization of S. aureus has been employed as a disease prevention strategy (Buehlmann et al, 2008; Coates et al, 2009) Antimicrobials such as mupirocin and/or chlorhexidine can be administered to high-risk patients as a means to decolonize these individual and to decrease the potential for subsequent infections; several studies have shown decolonization with these agents as a successful means of reducing HA-MRSA infections (Buehlmann et al, 2008; Septimus and Schweizer, 2016). These successful colonization interventions within the hospital setting have prompted calls for a similar approach for the prevention of CA-MRSA (Fritz et al, 2011; Ellis et al, 2014; Karanika et al, 2016; Tidwell et al, 2016)

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Results

Conclusion