The type VII secretion system of Staphylococcus aureus secretes a nuclease toxin
that targets competitor bacteria
#MMPMID27723728
Cao Z
; Casabona MG
; Kneuper H
; Chalmers JD
; Palmer T
Nat Microbiol
2016[Oct]; 2
(?): 16183
PMID27723728
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The type VII protein secretion system (T7SS) plays a critical role in the
virulence of human pathogens including Mycobacterium tuberculosis and
Staphylococcus aureus. Here, we report that the S. aureus T7SS secretes a large
nuclease toxin, EsaD. The toxic activity of EsaD is neutralized during its
biosynthesis through complex formation with an antitoxin, EsaG, which binds to
its C-terminal nuclease domain. The secretion of EsaD is dependent on a further
accessory protein, EsaE, that does not interact with the nuclease domain, but
instead binds to the EsaD N-terminal region. EsaE has a dual cytoplasmic/membrane
localization, and membrane-bound EsaE interacts with the T7SS secretion ATPase,
EssC, implicating EsaE in targeting the EsaDG complex to the secretion apparatus.
EsaD and EsaE are co-secreted, whereas EsaG is found only in the cytoplasm and
may be stripped off during the secretion process. Strain variants of S. aureus
that lack esaD encode at least two copies of EsaG-like proteins, most probably to
protect themselves from the toxic activity of EsaD secreted by esaD(+) strains.
In support of this, a strain overproducing EsaD elicits significant growth
inhibition against a sensitive strain. We conclude that the T7SS may play
unexpected and key roles in bacterial competitiveness.
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