Fitness costs associated with carriage of a large staphylococcal plasmid are reduced by subinhibitory concentrations of antiseptics

Abstract

Staphylococcus aureus carries a collection of mobile genetic elements that often harbor virulence and antimicrobial resistance genes. Since the introduction of antibiotics, plasmids have become a major genetic element responsible for the distribution of antimicrobial resistance. Under antimicrobial selection, resistance plasmids are maintained within bacterial populations as a means to ensure survival. However, in the absence of selection, large plasmids can be lost due to the fitness costs associated with harboring these genetic elements. pC02 is a previously identified multidrug resistance, conjugative plasmid that is found in S. aureus. In addition to antibiotic resistance, pC02 also carries genes known to be associated with antiseptic resistance.Among these, we previously characterized the contribution of qacA to pC02 mediated reduced chlorhexidine susceptibility. Herein, we demonstrate that pC02 also mediates triclosan resistance, likely due to the presence of fabI, a known triclosan resistance gene. Moreover, we demonstrate that conjugative transfer of pC02 increases triclosan resistance in recipient cells. Competition assays demonstrated a fitness cost associated with carriage of the large pC02 plasmid. However, subinhibitory concentrations of either chlorhexidine or triclosan abrogated this fitness cost. Given the widespread use of these antiseptics, both of which accumulate in wastewater and other environmental reservoirs, indiscriminate use of antiseptics likely imposes a constant selective pressure that promotes maintenance of antimicrobial resistance factors within S. aureus. K E Y W O R D Santibiotic resistance, bacterial plasmids, mobile genetic elements, Staphylococcus

The honeybee gut resistome and its role in antibiotic resistance dissemination

“…2017), suggesting that biofilm in honeybee gut perhaps has an equal role, which has not yet been clarified. Subinhibitory concentrations of antiseptics can reduce the fitness cost associated with plasmid carriage as well (LaBreck & Merrell 2020).…”

“…Biofilms always generate and maintain a large diversity of ARB that better retain a multi-drugresistant plasmid than the ancestor (Ridenhour et al 2017), suggesting that biofilm in honeybee gut perhaps has an equal role, which has not yet been clarified. Subinhibitory concentrations of antiseptics can reduce the fitness cost associated with plasmid carriage as well (LaBreck & Merrell 2020).…”

Large-Scale Analysis of Fitness Cost of tet(X4)-Positive Plasmids in Escherichia coli

“…However, the massive use of antibiotics has led to the emergence of multidrugresistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) bacteria, which severely diminishes the efficacy of clinically relevant antibiotics and constitutes a global public health problem (Zhong et al, 2014;Fang et al, 2020). Tigecycline is a broad-spectrum antibacterial drug of the glycyltetracyclines and has great antibacterial activity against hard-to-treat drug-resistant pathogens such as methicillin-resistant Staphylococcus aureus and carbapenemresistant pathogens (Labreck and Merrell, 2020;Xu et al, 2021a). In clinic, tigecycline is widely used in the treatment of abdominal infections, complicated skin and skin and soft tissue infections, and community-acquired pneumonia (Ni et al, 2016).…”