Abstract
Within a sufficiently large bacterial population, some members will naturally adopt an alternate, metabolically-active state that favors small molecule synthesis over cell division. These isogenic “tolerant” subpopulations have variable responses during antibiotic exposure and can remain viable in the presence of typically bactericidal concentrations. In this study, we determine the ability of typical and atypical antistaphylococcal therapies to reduce the viability of mupirocin-induced tolerant Staphylococcus aureus bacteria. Overall, tolerance-induced staphylococci exhibited a markedly decreased rate and extent of killing following antibiotic exposure. However, oritavancin remained effective at maintaining a similar extent of killing. Further studies to investigate the role of oritavancin against recurrent or relapse staphylococcal infection are warranted.
Highlights
Staphylococcus aureus is the most common invasive human pathogen and remains a major contributor to infection-related morbidity and mortality [1]
Antimicrobial tolerance occurs when a small fraction of a bacterial population ceases to focus on cell division and shifts to an alternate metabolic program favoring small molecule synthesis over growth [4,5]
Antimicrobial tolerance is associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) endovascular infection and poor clinical outcome [3]
Summary
Staphylococcus aureus is the most common invasive human pathogen and remains a major contributor to infection-related morbidity and mortality [1]. It has become clear that antibiotic tolerance can contribute to unfavorable clinical outcomes [3]. Antimicrobial tolerance occurs when a small fraction of a bacterial population ceases to focus on cell division and shifts to an alternate metabolic program favoring small molecule synthesis over growth [4,5]. In S. aureus, this process can be sharply accelerated by multiple factors present during infection including nutrient limitation, host cationic peptide exposure and polymorphonuclear neutrophil internalization [6,7]. Antimicrobial agents in clinical use are typically most effective against rapidly dividing bacteria, allowing this isogenic subpopulation to survive in otherwise bactericidal concentrations. Survivors of the antibiotic exposure can restart cell division upon cessation of antibiotics and cause relapse or recurrent infection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
