Uncover genetic determinants involved in the oxacillin tolerance phenotype of clinical methicillin-susceptible Staphylococcus aureus isolates
Duration: 44 weeks (School year internship (full time), Master’s thesis)
BACKGROUND
Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of hospital-, community-, and livestock-associated infections and is listed, as a high priority pathogen by the World Health Organization (WHO). S. aureus is a versatile microbe that can evolve rapidly to adapt to new environmental conditions. Under antibiotic pressure, for instance, S. aureus can escape the killing action of antibiotics by entering in a tolerant, non-dividing physiological state, becoming undetectable to clinicians. This adaptive behavior does not imply a change in the level of resistance. This phenomenon may lead to misclassification of tolerant strains as resistant, or vice versa, resulting in ineffective treatments. Once the antibiotic is removed, tolerant bacteria can resume their growth and lead to recurrent infections. Recent in vitro and in vivo studies showed that intermittent antibiotic exposures, the most common therapy approach used to treat patients, lead to the rapid evolution of tolerance followed by emergence of resistance, stressing the possible threat to human health. In a previous study, we identified, through whole-genome sequencing (WGS), genes that may be involved in the tolerance phenotype in clinical methicillin-susceptible S. aureus isolates recovered from bloodstream infection samples.
OBJECTIVES
The goal of this project is to produce proof for the concept that the identified genes may be involved on the β-lactam tolerance phenotype in S. aureus.