The Serine Protease Autotransporter Pic Modulates Citrobacter rodentium Pathogenesis and Its Innate Recognition by the Host

Bhullar, Kirandeep; Zarepour, Maryam; Yu, Hongbing; Yang, Hong; Croxen, Matthew; Stahl, Martin; Finlay, B. Brett; Turvey, Stuart E.; Vallance, Bruce A.

doi:10.1128/iai.00025-15

Cited by 29Escherichia coli research studiesBacterial Genetics and BiotechnologyEnterobacteriaceae and Cronobacter Research

The Serine Protease Autotransporter Pic Modulates Citrobacter rodentium Pathogenesis and Its Innate Recognition by the Host

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Bhullar, Kirandeep, Zarepour, Maryam, Yu, Hongbing, Yang, Hong, Croxen, Matthew, Stahl, Martin, Finlay, B. Brett, Turvey, Stuart E. +1 more·2015·Infection and Immunity

DOI 10.1128/iai.00025-15PMC PMC4468532

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Abstract

Bacterial pathogens produce a number of autotransporters that possess diverse functions. These include the family of serine protease autotransporters of Enterobacteriaceae (SPATEs) produced by enteric pathogens such as Shigella flexneri and enteroaggregative Escherichia coli . Of these SPATEs, one termed “protein involved in colonization,” or Pic, has been shown to possess mucinase activity in vitro , but to date, its role in in vivo enteric pathogenesis is unknown. Testing a pic null (Δ picC ) mutant in Citrobacter rodentium , a natural mouse pathogen, found that the C. rodentium Δ picC strain was impaired in its ability to degrade mucin in vitro compared to the wild type. Upon infection of mice, the Δ picC mutant exhibited a hypervirulent phenotype with dramatically heavier pathogen burdens found in intestinal crypts. Δ picC mutant-infected mice suffered greater barrier disruption and more severe colitis and weight loss, necessitating their euthanization between 10 and 14 days postinfection. Notably, the virulence of the Δ picC mutant was normalized when the picC gene was restored; however, a PicC point mutant causing loss of mucinase activity did not replicate the Δ picC phenotype. Exploring other aspects of PicC function, the Δ picC mutant was found to aggregate to higher levels in vivo than wild-type C. rodentium . Moreover, unlike the wild type, the C. rodentium Δ picC mutant had a red, dry, and rough (RDAR) morphology in vitro and showed increased activation of the innate receptor Toll-like receptor 2 (TLR2). Interestingly, the C. rodentium Δ picC mutant caused a degree of pathology similar to that of wild-type C. rodentium when infecting TLR2-deficient mice, showing that despite its mucinase activity, PicC's major role in vivo may be to limit C. rodentium 's stimulation of the host's innate immune system.

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The serine protease Pic produced by E. coli (EAEC), Citrobacter and Shigella flexneri is a virulence factor associated with adherence, colonization and evasion of the innate immune system.
“the serine protease Pic produced by E. coli (EAEC), Citrobacter and Shigella flexneri is a virulence factor associated with adherence, colonization and evasion of the innate immune system.68–71”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [70]

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Authors: Bhullar, K., Zarepour, M., Yu, H., Yang, H., Croxen, M., Stahl, M., Finlay, B. B., Turvey, S. E., & Vallance, B. A.
Affiliations: Child and Family Research Institute (CA)
University of British Columbia (CA)
ORCID: Yang, Hong
Croxen, Matthew
Finlay, B. Brett
Turvey, Stuart E.
Vallance, Bruce A.
Venue: Infection and Immunity
Publisher: American Society for Microbiology
Published: 2015-07
Volume: 83
Issue: 7
Pages: 2636-2650
ISSN: 0019-9567 (ISSN-L)
1098-5522
DOI: 10.1128/iai.00025-15
PMC: PMC4468532
OpenAlex: W2129028798
Cited by: 29
References: 51
Citations by year: 2026: 2 · 2025: 5 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 3
FWCI: 1.55
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Infection and Immunity (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: University of British Columbia
Canadian Institutes of Health Research
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Enterobacteriaceae and Cronobacter Research
Keywords: peripherally inserted central catheter, Citrobacter rodentium, mucin degradation, bacterial virulence, innate immune recognition, TLR2, colitis, intestinal barrier disruption, bacterial aggregation, host-pathogen interaction
MeSH terms: Animals, Enterobacteriaceae Infections, Genetic Complementation Test, Hydrolysis, Mice, Inbred C57BL, Mucins, Gene Deletion, Point Mutation, Virulence Factors, Citrobacter rodentium, Serine Proteases, Proteolysis

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The Serine Protease Autotransporter Pic Modulates Citrobacter rodentium Pathogenesis and Its Innate Recognition by the Host

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