A small membrane stabilising protein critical to the pathogenicity of Staphylococcus aureus

Seána Duggan, Maisem Laabei, Alaa Alnahari, Eoin T O'Brien, Keenan Lacey, Leann Bacon, Kate J Heesom, Chih-Lung Fu, Michael Otto, Eric Skaar, Rachel M McLoughlin, Ruth C Massey

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Abstract

Staphylococcus aureus is a major human pathogen, where the emergence of antibiotic resistant strains is making all types of S. aureus infections more challenging to treat. With a pressing need to develop alternative control strategies to use alongside or in place of conventional antibiotics, one approach is the targeting of established virulence factors. However, attempts at this have had little success to date, suggesting that we need to better understand how this pathogen causes disease if effective targets are to be identified. To address this, using a functional genomics approach we have identified a small membrane bound protein that we have called MspA. Inactivation of this protein results in the loss of the ability of S. aureus to secrete cytolytic toxins, protect itself from several aspects of the human innate immune system and control its iron homeostasis. These changes appear to be mediated though a change in the stability of the bacterial membrane as a consequence of iron toxicity. These pleiotropic effects on the ability of the pathogen to interact with its host result in a significant impairment in the ability of S. aureus to cause infection in both a subcutaneous and sepsis model of infection. Given the scale of the effect the inactivation of MspA causes, it represents a unique and promising target for the development of a novel therapeutic approach.
Original languageEnglish
Article number e00162-20
Number of pages20
JournalInfection and Immunity
Early online date19 Aug 2020
DOIs
Publication statusE-pub ahead of print - 19 Aug 2020

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