Research Topic

Role Of Small Colony Variants (SCVs) And Persisters In Staphylococcus aureus Pathogenesis And Development Of Therapeutic Approaches

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Staphylococcus aureus is a facultative pathogenic bacterium that can colonize the epithelial surface of many healthy individuals but is also one of the most frequent causes of sepsis, endocarditis, and osteomyelitis. This pathogen is one of the main causes of chronic and therapy-refractory infections which ...

Staphylococcus aureus is a facultative pathogenic bacterium that can colonize the epithelial surface of many healthy individuals but is also one of the most frequent causes of sepsis, endocarditis, and osteomyelitis. This pathogen is one of the main causes of chronic and therapy-refractory infections which are an unsolved clinical problem despite the availability of antibiotics to which the bacterium is susceptible.
Chronic staphylococcal infections have been linked to different adaptive strategies that these bacteria use to survive in the intracellular environment, during biofilm formation, and to evade the host response. The persistent phenotype includes bacteria in a dormant, non-growing state such as small colony variants (SCVs) as well as non-SCV S. aureus persisters and L-form bacteria (i.e., cell-wall-deficient bacteria). Due to slow metabolism, SCVs are phenotypically resistant to several antibiotics and cannot produce virulence factors. The long-term persistence of SCVs in the host tissue is facilitated by the non-activation of the host defenses and in the intracellular survival where the bacteria are largely protected against antimicrobial treatments and the host immune system. The intracellular localization may be temporal and represents a possible reservoir of S. aureus. However, SCVs can leave the intracellular shelter and revert to the fully-aggressive wild-type phenotype that can initiate a new episode of infection. Several factors were described as inducers of SCVs such as gentamycin, the concentration of oxygen, pH and oxidative burst among others. However, it is still unclear whether SCVs are part of the initial bacterial population or they are induced in the intracellular environment or whether both processes may happen during the process of infection.
Additionally, heterogeneity within bacterial populations can explain the successful survival of S. aureus. The heterogeneity may involve several alternative mechanisms to SCV and non-SCV persister formation which allow S. aureus to survive extracellularly and within the host cells, and evade the host immune system.

New alternative infection models are required to study the development/selection of SCVs and non-SCV persisters during the process of infections. Also, a better understanding of the molecular pathways involved in the formation of SCVs as well as of persistence in non-SCV, and of cell death mechanisms are needed in order to design improved treatments for chronic infections.
This Research Topic investigates the interplay/evolution between host and pathogen during the S. aureus infection and will help to optimize treatment strategies for invasive and therapy-refractory infection courses. Sub-topics of interest include:
1- Investigate host signals that impact on S. aureus phenotype switch from wild type to dormant state, affecting the heterogeneity in the bacterial population
2- Study molecular mechanism involved in persistence and cell death of S. aureus
3- Develop models in vivo and in vitro to study persistent infections and interaction host-pathogen from acute to chronic infection
The following article types are particularly welcomed:
• Original articles
• Review
• Mini Review
• Perspective


Keywords: S. aureus, Persisters, Small Colony Variants, Pathogenesis, Antimicrobial Treatment


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