Loading…
The msaABCR Operon Regulates Persister Formation by Modulating Energy Metabolism in Staphylococcus aureus
is a major human pathogen that causes chronic, systemic infections, and the recalcitrance of these infections is mainly due to the presence of persister cells, which are a bacterial subpopulation that exhibits extreme, yet transient, antibiotic tolerance accompanied by a transient halt in growth. Ho...
Saved in:
Published in: | Frontiers in microbiology 2021-04, Vol.12, p.657753-657753 |
---|---|
Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | is a major human pathogen that causes chronic, systemic infections, and the recalcitrance of these infections is mainly due to the presence of persister cells, which are a bacterial subpopulation that exhibits extreme, yet transient, antibiotic tolerance accompanied by a transient halt in growth. However, upon cessation of antibiotic treatment, a resumption in growth of persister cells causes recurrence of infections and treatment failure. Previously, we reported the involvement of
in several important staphylococcal phenotypes, including the formation of persister cells. Additionally, observations of the regulation of several metabolic genes by the
operon in transcriptomics and proteomics analyses have suggested its role in the metabolic activities of
. Given the importance of metabolism in persister formation as our starting point, in this study we demonstrated how the
operon regulates energy metabolism and subsequent antibiotic tolerance. We showed that deletion of the
operon results in increased tricarboxylic acid (TCA) cycle activity, accompanied by increased cellular ATP content and higher NADH content in
cells. We also showed that
(through MsaB) represses the
and
genes, thereby regulating TCA cycle activity and the generation of membrane potential, respectively. Together, the observations from this study led to the conclusion that
operon deletion induces a metabolically hyperactive state, leading to decreased persister formation in
. |
---|---|
ISSN: | 1664-302X 1664-302X |
DOI: | 10.3389/fmicb.2021.657753 |