Surface-Layer Protein A (SlpA) Is a Major Contributor to Host-Cell Adherence of Journal Article

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Authors: Merrigan, M. M.; Venugopal, A.; Roxas, J. L.; Anwar, F.; Mallozzi, M. J.; Roxas, B. A.; Gerding, D. N.; Viswanathan, V. K.; Vedantam, G.
Article Title: Surface-Layer Protein A (SlpA) Is a Major Contributor to Host-Cell Adherence of
Abstract: Clostridium difficile is a leading cause of antibiotic-associated diarrhea, and a significant etiologic agent of healthcare-associated infections. The mechanisms of attachment and host colonization of C. difficile are not well defined. We hypothesize that non-toxin bacterial factors, especially those facilitating the interaction of C. difficile with the host gut, contribute to the initiation of C. difficile infection. In this work, we optimized a completely anaerobic, quantitative, epithelial-cell adherence assay for vegetative C. difficile cells, determined adherence proficiency under multiple conditions, and investigated C. difficile surface protein variation via immunological and DNA sequencing approaches focused on Surface-Layer Protein A (SlpA). In total, thirty-six epidemic-associated and non-epidemic associated C. difficile clinical isolates were tested in this study, and displayed intra- and inter-clade differences in attachment that were unrelated to toxin production. SlpA was a major contributor to bacterial adherence, and individual subunits of the protein (varying in sequence between strains) mediated host-cell attachment to different extents. Pre-treatment of host cells with crude or purified SlpA subunits, or incubation of vegetative bacteria with anti-SlpA antisera significantly reduced C. difficile attachment. SlpA-mediated adherence-interference correlated with the attachment efficiency of the strain from which the protein was derived, with maximal blockage observed when SlpA was derived from highly adherent strains. In addition, SlpA-containing preparations from a non-toxigenic strain effectively blocked adherence of a phylogenetically distant, epidemic-associated strain, and vice-versa. Taken together, these results suggest that SlpA plays a major role in C. difficile infection, and that it may represent an attractive target for interventions aimed at abrogating gut colonization by this pathogen.
Journal Title: PloS one
Volume: 8
Issue: 11
ISSN: 1932-6203; 1932-6203
Publisher: Unknown  
Date Published: 2013
Start Page: e78404
Language: ENG
DOI/URL:

10.1371/journal.pone.0078404
Notes: JID: 101285081; 2013 [ecollection]; 2013/05/29 [received]; 2013/09/11 [accepted]; 2013/11/12 [epublish]; epublish