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Updated: Nov 19, 2025
Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Recalcitrant Staphylococcus aureus Infections: Obstacles and Solutions
Sarah E Rowe1, Jenna E Beam1, Brian P Conlon2,3
1Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Abstract:
Antibiotic treatment failure of Staphylococcus aureus infections is very common. In addition to genetically encoded mechanisms of antibiotic resistance, numerous additional factors limit the efficacy of antibiotics in vivo Identifying and removing the barriers to antibiotic efficacy are of major importance, as even if new antibiotics become available, they will likely face the same barriers to efficacy as their predecessors. One major obstacle to antibiotic efficacy is the proficiency of S. aureus to enter a physiological state that is incompatible with antibiotic killing. Multiple pathways leading to antibiotic tolerance and the formation of tolerant subpopulations called persister cells have been described for S. aureus Additionally, S. aureus is a versatile pathogen that can infect numerous tissues and invade a variety of cell types, of which some are poorly penetrable to antibiotics. It is therefore unlikely that there will be a single solution to the problem of recalcitrant S. aureus infection. Instead, specific approaches may be required for targeting tolerant cells within different niches, be it through direct targeting of persister cells, sensitization of persisters to conventional antibiotics, improved penetration of antibiotics to particular niches, or any combination thereof. Here, we examine two well-described reservoirs of antibiotic-tolerant S. aureus, the biofilm and the macrophage, the barriers these environments present to antibiotic efficacy, and potential solutions to the problem.
Insights
Antibiotic treatment failure in Staphylococcus aureus infections is common due to bacterial tolerance and poor drug penetration. Strategies targeting tolerant cells in biofilms and macrophages are crucial for effective treatment.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Antibiotic treatment failure for Staphylococcus aureus infections is a significant clinical challenge.
- Bacterial antibiotic resistance is exacerbated by factors beyond genetic encoding, limiting antibiotic efficacy in vivo.
- Staphylococcus aureus exhibits tolerance by entering physiological states resistant to antibiotics, forming persister cells.
Purpose of the Study:
- To investigate barriers to antibiotic efficacy against Staphylococcus aureus.
- To examine antibiotic tolerance in Staphylococcus aureus within specific host niches.
- To explore potential strategies for overcoming antibiotic recalcitrance in Staphylococcus aureus infections.
Main Methods:
- Review of literature on Staphylococcus aureus antibiotic tolerance and resistance mechanisms.
- Analysis of factors affecting antibiotic penetration into various host tissues and cell types.
- Examination of biofilm and macrophage environments as reservoirs for antibiotic-tolerant Staphylococcus aureus.
Main Results:
- Staphylococcus aureus employs multiple pathways to achieve antibiotic tolerance, including the formation of persister cells.
- The pathogen's ability to infect diverse tissues and invade poorly penetrable cell types creates barriers to antibiotic treatment.
- Biofilms and macrophages represent key niches where Staphylococcus aureus exhibits significant antibiotic tolerance.
Conclusions:
- A single solution for recalcitrant Staphylococcus aureus infections is unlikely due to the pathogen's versatility.
- Targeting tolerant cells, sensitizing persisters, or improving antibiotic penetration are potential strategies.
- Addressing antibiotic tolerance within specific niches like biofilms and macrophages is essential for improving treatment outcomes.
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