How much is enough?

Oeiras, 11.05.2015

Many biological processes require an organized ensemble of different proteins. But are all of those proteins equally necessary? Or are some proteins more important than others for a particular process to occur? Researchers from the labs of Bacterial Cell Biology and Bacterial Cell Surfaces and Pathogenesis, and collaborators, decided to answer this question for the synthesis of a bacterial cell wall material, the peptidoglycan. The results now published in PLOS Pathogens show that only two out of the nine proteins known to be involved in the synthesis of peptidoglycan are necessary for Staphylococcus aureus to thrive in the lab. Still, things might be more complicated in real life.

Knowing the minimal requirements for bacteria to function helps identifying essential targets for the unfair war against antibiotic resistance and this is particularly relevant for Staphylococcus aureus. Contemporary antibiotics target the peptidoglycan synthesis machine and this study exposes which of the enzymes involved in the final stages of the process are the most vulnerable and thus most attractive for developing new drugs or new strategies to increase the efficacy of available antibiotics.

In order to identify the minimal functional unit necessary for peptidoglycan synthesis, researchers produced different strains of Staphylococcus aureus, deleting, in various combinations, some of nine genes known to be involved in the last stages of peptidoglycan synthesis. Two specific genes were enough to ensure this process, and the bacterial cells with these two genes were able to grow and divide in vitro. However, when challenged in a more realistic environment, like in the presence of antibiotics or in a Drosophila fly infection model, these bacteria showed loss of resistance and decreased virulence, highlighting the role of non-essential enzymes for bacterial survival in the host.

In their paper, researchers point out another application for the identification of minimal functional units of molecular machines, which is the expanding field of synthetic biology: pinpointing the essential biological components should help designing systems with reduced complexity.

This work involved researchers from ITQB, University of Oxford (UK), Instituto Gulbenkian de Ciência (Portugal), Johns Hopkins Bloomberg School of Public Health (USA), The University of Sheffield (UK), and Merck Research Laboratories (USA).
 

Original Article

PLOS Pathogens (2015) DOI: 10.1371/journal.ppat.1004891

Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance

Patricia Reed, Magda L. Atilano, Renato Alves, Egbert Hoiczyk, Xinwei Sher, Nathalie T. Reichmann, Pedro M. Pereira, Terry Roemer, Sérgio R. Filipe, José B. Pereira-Leal, Petros Ligoxygakis, Mariana G. Pinho.