Unravelling the mechanisms for recruitment and activation of septal peptidoglycan hydrolases in Staphylococcus aureus

Peptidoglycan (PG) hydrolases are instrumental in mediating bacterial daughter cell separation via septum splitting, an essential process for the ability of bacteria to multiply.

In a gram-positive pathogen such as Staphylococcus aureus, the division septum is completed before PG hydrolases initiate septum splitting. S. aureus is an important pathogen, as it is one of the most common causes of death by antibiotic resistant infections.

Premature splitting of the division septum could expose an immature bacterial cell surface, devoid of virulence factors, leading to pathogen elimination by the innate immune system of an infected host.

Hence, the activity of PG hydrolases must be tightly regulated to avoid deleterious effects on bacteria, including lysis-inducing breaches in the cell surface that would lead to bacterial death. S. aureus encodes 19 PG hydrolases, most of which have ill-characterized functions and regulation mechanisms.

In this project I will identify the complete set of PG hydrolases that have a role in septum splitting, uncover their mechanisms of localization to the division septum and identify how they are regulated during the cell cycle and particularly what triggers their activation to initiate septum splitting at the right timing.

For this I will join the laboratory of Prof.

Mariana Pinho ITQB Universidade NOVA de Lisboa, due to their unmatchable expertise in the field of staphylococcal cell wall biology and their commitment to promote my career development during the MSCA-PF project.

This fellowship is a unique opportunity to develop my research and complementary skills, acting as a critical stepping-stone towards a tenure-track faculty position.