Dataset Information

Activation of the extracytoplasmic function ? factor ?^V by lysozyme.

ABSTRACT: ?^V is an extracytoplasmic function (ECF) ? factor that is found exclusively in Firmicutes including Bacillus subtilis and the opportunistic pathogens Clostridioides difficile and Enterococcus faecalis. ?^V is activated by lysozyme and is required for lysozyme resistance. The activity of ?^V is normally inhibited by the anti-? factor RsiV, a transmembrane protein. RsiV acts as a receptor for lysozyme. The binding of lysozyme to RsiV triggers a signal transduction cascade which results in degradation of RsiV and activation of ?^V . Like the anti-? factors for several other ECF ? factors, RsiV is degraded by a multistep proteolytic cascade that is regulated at the step of site-1 cleavage. Unlike other anti-? factors, site-1 cleavage of RsiV is not dependent upon a site-1 protease whose activity is regulated. Instead constitutively active signal peptidase cleaves RsiV at site-1 in a lysozyme-dependent manner. The activation of ?^V leads to the transcription of genes, which encode proteins required for lysozyme resistance.

SUBMITTER: Ho TD

PROVIDER: S-EPMC6703919 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Activation of the extracytoplasmic function σ factor σV by lysozyme.

Ho Theresa D TD Ellermeier Craig D CD

Molecular microbiology 20190718 2

σV is an extracytoplasmic function (ECF) σ factor that is found exclusively in Firmicutes including Bacillus subtilis and the opportunistic pathogens Clostridioides difficile and Enterococcus faecalis. σV is activated by lysozyme and is required for lysozyme resistance. The activity of σV is normally inhibited by the anti-σ factor RsiV, a transmembrane protein. RsiV acts as a receptor for lysozyme. The binding of lysozyme to RsiV triggers a signal transduction ca ...[more]

PMID: 31286585

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Project description:Clostridioides (Clostridium) difficile is one of the leading causes of nosocomial diarrhea. Lysozyme is a common host defense against many pathogenic bacteria. C. difficile exhibits high levels of lysozyme resistance, which is due in part to the extracytoplasmic functioning (ECF) σ factor, σV. It has been previously demonstrated that genes regulated by σV are responsible for peptidoglycan modifications that provide C. difficile with high lysozyme resistance. σV is not unique to C. difficile however, and its role in lysozyme resistance and its mechanism of activation has been well characterized in Bacillus subtilis where the anti-σ, RsiV, sequesters σV until lysozyme directly binds to RsiV, activating σV. However, it remains unclear if the mechanism of σV activation is similar in C. difficile. Here, we investigated how activation of σV is controlled in C. difficile by lysozyme. We found that C. difficile RsiV was degraded in the presence of lysozyme. We also found that disruption of a predicted signal peptidase cleavage site blocked RsiV degradation and σV activation, indicating that the site-1 protease is likely a signal peptidase. We also identified a conserved site-2 protease, RasP, that was required for site-2 cleavage of RsiV and σV activation in response to lysozyme. Combined with previous work showing RsiV directly binds lysozyme, these data suggested that RsiV directly binds lysozyme in C. difficile, which leads to RsiV destruction via cleavage at site-1 by signal peptidase and then at site-2 by RasP, ultimately resulting in σV activation and increased resistance to lysozyme. IMPORTANCE Clostridioides difficile is a major cause of hospital-acquired diarrhea and represents an urgent concern due to the prevalence of antibiotic resistance and the rate of recurrent infections. We previously showed that σV and the regulon under its control were involved in lysozyme resistance. We have also shown in B. subtilis that the anti-σ RsiV acts as a direct sensor for lysozyme. which results in the destruction of RsiV and activation of σV. Here, we described the proteases required for degradation of RsiV in C. difficile in response to lysozyme. Our data indicated that the mechanism is highly conserved between B. subtilis and C. difficile.

Dataset Information

Activation of the extracytoplasmic function ? factor ?^V by lysozyme.

Publications

Activation of the extracytoplasmic function σ factor σ<sup>V</sup> by lysozyme.

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Dataset Information

Activation of the extracytoplasmic function ? factor ?V by lysozyme.

Publications

Activation of the extracytoplasmic function σ factor σ<sup>V</sup> by lysozyme.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Activation of the extracytoplasmic function ? factor ?^V by lysozyme.