Proteolytic activity of surface exposed HtrA determines its expression level and is needed to survive acidic conditions in Clostridioides difficile
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract To survive in the host, pathogenic bacteria need to be able to react to the unfavourable conditions that they encounter, like low pH, elevated temperatures, antimicrobial peptides and many more. These conditions may lead to unfolding of envelope proteins and this may be lethal. One of the mechanisms through which bacteria are able to survive these conditions is through the protease/foldase activity of the high temperature requirement A (HtrA) protein. The gut pathogen Clostridioides difficile encodes one HtrA homolog that is predicted to contain a membrane anchor and a single PDZ domain. The function of HtrA in C. difficile is hitherto unknown but previous work has shown that an insertional mutant of htrA displayed elevated toxin levels, less sporulation and decreased binding to target cells. Here, we show that HtrA is membrane associated and localized on the surface of C. difficile and characterize the requirements for proteolytic activity of recombinant soluble HtrA. In addition, we show that the level of HtrA in the bacteria heavily depends on its proteolytic activity. Finally, we show that proteolytic activity of HtrA is required for survival under acidic conditions.
Authors 7
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Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center of Infectious Diseases (LUCID), Leiden University Medical Center, Leiden The Netherlands
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Bart Claushuis Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center of Infectious Diseases (LUCID), Leiden University Medical Center, Leiden The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden The Netherlands
Leiden University Center of Infectious Diseases (LUCID), Leiden University Medical Center, Leiden The Netherlands
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Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden The Netherlands
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Merle M. van Leeuwen Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center of Infectious Diseases (LUCID), Leiden University Medical Center, Leiden The Netherlands
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Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden The Netherlands
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Wiep Klaas Smits Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center of Infectious Diseases (LUCID), Leiden University Medical Center, Leiden The Netherlands
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