Phenotypic Switching of Staphylococcus aureus Mu50 Into a Large Colony Variant Enhances Heritable Resistance Against β-Lactam Antibiotics.

Yajun Sun,Xin Zhao,Miaomiao Liu,Mingze Niu

doi:10.3389/fmicb.2021.709841

Yajun Sun, Xin Zhao + Show 2 more

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https://doi.org/10.3389/fmicb.2021.709841

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Abstract

Phenotypic heterogeneity within a bacterial population may confer new functionality and allow microorganisms to adapt to fluctuating environments. Previous work has suggested that Staphylococcus aureus could form small colony variants to avoid elimination by therapeutic antibiotics and host immunity systems. Here we show that a reversible non-pigment large colony morphology (Mu50∆lcpA-LC) was observed in S. aureus Mu50 after knocking out lcpA, coding for the LytR-CpsA-Psr family A protein. Mu50∆lcpA-LC increased resistance to β-lactam antibiotics, in addition, the enlarged cell size, enhanced spreading ability on solid medium, and reduced biofilm formation, suggesting better abilities for bacterial expansion. Moreover, the expression of spa encoding protein A was significantly increased in Mu50∆lcpA-LC. This study shows that besides the small colony variants, S. aureus could fight against antibiotics and host immunity through phenotype switching into a large colony variant.

Highlights

Staphylococcus aureus is an important human opportunistic pathogen that commonly colonizes the skin, mucosal surfaces, and soft tissues
The targets for β-lactam antibiotics are known as penicillin-binding proteins (PBPs). β-Lactam antibiotics inhibit the last step in peptidoglycan synthesis by acylating the penicillin-binding proteins involved in cross-linking peptides to form peptidoglycan, which is a vital constituent of the bacterial cell wall
Our results suggest that the S. aureus can evolve in response to antibiotic stress and host immunity system by phenotypic switching

Summary

Introduction

Staphylococcus aureus is an important human opportunistic pathogen that commonly colonizes the skin, mucosal surfaces, and soft tissues. S. aureus has been notoriously able to acquire resistance to a variety of antibiotics. The targets for β-lactam antibiotics are known as penicillin-binding proteins (PBPs). Β-Lactam antibiotics inhibit the last step in peptidoglycan synthesis by acylating the penicillin-binding proteins involved in cross-linking peptides to form peptidoglycan, which is a vital constituent of the bacterial cell wall. The increasing use of β-lactams has resulted in the worldwide spread of the methicillin-resistant S. aureus (MRSA; Lee et al, 2018). The resistance of MRSA is usually conferred by acquisition of a low-affinity penicillin-binding protein 2A (Hartman and Tomasz, 1984)

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