Genetic competence for natural transformation in Staphylococcus aureus: how does an important human pathogen accumulate antibiotic resistances?
Abstract:
Antimicrobial Resistance (AMR) represents a major global public health threat, often referred to as a “hidden pandemic”. Among the bacterial pathogens involved, Staphylococcus aureus is of particular concern due to its ability to acquire and accumulate AMR genes through Horizontal Gene Transfer (HGT). A prominent example is the transfer of the Staphylococcal
Cassette Chromosome mec (SCCmec), which confers methicillin resistance. To date, this transfer has only been demonstrated via Natural Transformation (NT), one of the three main HGT transfer mechanisms. This process requires bacteria to enter a differentiated state called genetic competence, which has only recently been identified in S. aureus.
The aim of this project was to decipher the molecular and physiological mechanisms governing the genetic competence in S. aureus and to identify the environmental conditions that promote HGT in this major human pathogen. I demonstrated that NT is restricted to a transient “window”. Using firefly luciferase as a transcriptional reporter, I also characterized the
dynamics of NT genes expression and identified new regulatory mechanisms of the competence program with high temporal resolution.
In parallel, I have developed a Tn-FACSeq methodology in S. aureus combining transposon mutagenesis, flow cytometry and high-throughput sequencing, for which I generated a highly saturated S. aureus transposon-insertion library. This tool allowed the identification of new regulatory pathways and actors involved in the development of genetic competence.
Altogether, this work provides key insights into how S. aureus acquires AMR and contributes to a better understanding of the in vivo environmental conditions driving the emergence and dissemination of multidrug-resistant strains.
Rapporteur : Karen Moreau, Professeur des Universités - Université Claude Bernard (Lyon 1)
Rapporteur : Nathalie Campo, Chargée de Recherche, HDR - Université Paul Sabatier (Toulouse)
Examinateur : Peter Mergaert, Directeur de Recherche - Université Paris-Saclay
Examinateur : Yoann Augagneur, Professeur des Universités - Université de Rennes 1