Peptidoglycan hydrolases - an outlook to cell wall synthesis, remodeling and antimicrobial resistance in S. aureus
Perttu Permi
Department of Biological and Environmental Science, Department of Chemistry, Nanoscience Center,
University of Jyvaskyla, FI-40014, Jyvaskyla, Finland.
Abstract:
Antimicrobial resistance (AMR) is one of the most urgent threats to human health. It can affect anyone, regardless of health, age or country. As antibiotics become less effective, once easily treatable illnesses lead to dangerous, even fatal infections. AMR is the new long-standing pandemic - bacteria develop resistance at a pace faster than new therapeutics are approved. Access to affordable, effective drugs guarantees equal prospects for people wellbeing.
Staphylococcus aureus is among the most infamous pathogens and its resistance to antibiotics has increased rapidly - MRSA strains can be simultaneously resistant to different classes of antibiotics, including
the so-called “drugs of last resort” such as ceftaroline and vancomycin. The need for new drugs against resistant S. aureus is high.
We investigate enzymes that kill S. aureus by breaking glycine bonds in the peptidoglycan of S. aureus cell wall. Due to their binding specificity and lytic activity, these enzymes are attractive targets for drug development.
They can be exploited either by interfering with their tightly controlled regulation or alternatively by exogenous
administration.
In this talk, I will provide you with a comprehensive overview of peptidoglycan synthesis and cell wall remodeling in S. aureus. In addition, I will discuss our latest results regarding determination of the substrate specificity of S. aureus specific cell wall hydrolases and their implication in the PG remodeling (Antenucci et al., 2024). This knowledge is essential for understanding how these hydrolases degrade the cell wall and ascertain their applicability as next-generation antimicrobials.
References:
Lina Antenucci, Salla Virtanen, Chandan Thapa, Minne Jartti, Ilona Pitkänen, Helena Tossavainen, Perttu Permi (2024) Reassessing the substrate specificities of the major Staphylococcus aureus peptidoglycan hydrolases lysostaphin and LytM eLife 13:RP93673
