Flagellin is essential for initial attachment to mucosal surfaces by Clostridioides difficile

Ben Sidner; Armando Lerma; Baishakhi Biswas; Thi Van Thanh Do; Yafan Yu; Leslie A. Ronish; Hugh McCullough; Jennifer M. Auchtung; Kurt H. Piepenbrink

doi:10.1128/spectrum.02120-23

Microbiology Spectrum (Dec 2023)

Flagellin is essential for initial attachment to mucosal surfaces by Clostridioides difficile

Ben Sidner,
Armando Lerma,
Baishakhi Biswas,
Thi Van Thanh Do,
Yafan Yu,
Leslie A. Ronish,
Hugh McCullough,
Jennifer M. Auchtung,
Kurt H. Piepenbrink

Affiliations

Ben Sidner: Department of Food Science and Technology, University of Nebraska-Lincoln , Lincoln, Nebraska, USA
Armando Lerma: Department of Food Science and Technology, University of Nebraska-Lincoln , Lincoln, Nebraska, USA
Baishakhi Biswas: Department of Food Science and Technology, University of Nebraska-Lincoln , Lincoln, Nebraska, USA
Thi Van Thanh Do: Department of Food Science and Technology, University of Nebraska-Lincoln , Lincoln, Nebraska, USA
Yafan Yu: Department of Biochemistry, University of Nebraska-Lincoln , Lincoln, Nebraska, USA
Leslie A. Ronish: Department of Biochemistry, University of Nebraska-Lincoln , Lincoln, Nebraska, USA
Hugh McCullough: Department of Food Science and Technology, University of Nebraska-Lincoln , Lincoln, Nebraska, USA
Jennifer M. Auchtung: Department of Food Science and Technology, University of Nebraska-Lincoln , Lincoln, Nebraska, USA
Kurt H. Piepenbrink: Department of Food Science and Technology, University of Nebraska-Lincoln , Lincoln, Nebraska, USA

DOI: https://doi.org/10.1128/spectrum.02120-23
Journal volume & issue: Vol. 11, no. 6

Abstract

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ABSTRACT Mucins are glycoproteins which can be found in host cell membranes and as a gelatinous surface formed from secreted mucins. Mucosal surfaces in mammals form a barrier to invasive microbes, particularly bacteria, but are a point of attachment for others. Clostridioides difficile is an anaerobic bacterium, which colonizes the mammalian gastrointestinal (GI) tract and is a common cause of acute GI inflammation leading to a variety of negative outcomes. Although C. difficile toxicity stems from secreted toxins, colonization is a prerequisite for C. difficile disease. While C. difficile is known to associate with the mucous layer and underlying epithelium, the mechanisms underlying these interactions that facilitate colonization are less well understood. To understand the molecular mechanisms by which C. difficile interacts with mucins, we used ex vivo mucosal surfaces to test the ability of C. difficile to bind to mucins from different mammalian tissues. We found significant differences in C. difficile adhesion based upon the source of mucins, with highest levels of binding observed to mucins purified from the human colonic adenocarcinoma line LS174T and lowest levels of binding to porcine gastric mucin. We also observed defects in adhesion by mutants deficient in flagella but not type IV pili. These results imply that interactions between host mucins and C. difficile flagella facilitate the initial host attachment of C. difficile to host cells and secreted mucus. IMPORTANCE Clostridioides difficile is one of the leading causes of hospital-acquired infections worldwide and presents challenges in treatment due to recurrent gastrointestinal disease after treatment with antimicrobials. The mechanisms by which C. difficile colonizes the gut represent a key gap in knowledge, including its association with host cells and mucosa. Our results show the importance of flagellin for specific adhesion to mucosal hydrogels and can help to explain prior observations of adhesive defects in flagellin and pilin mutants.

Published in Microbiology Spectrum

ISSN: 2165-0497 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/spectrum

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