title: The dlt operon confers resistance to cationic antimicrobial peptides in Clostridium difficile.
abstract: The dlt operon in Gram-positive bacteria encodes proteins that are necessary for the addition of d-alanine to teichoic acids of the cell wall. The addition of d-alanine to the cell wall results in a net positive charge on the bacterial cell surface and, as a consequence, can decrease the effectiveness of antimicrobials, such as cationic antimicrobial peptides (CAMPs). Although the roles of the dlt genes have been studied for some Gram-positive organisms, the arrangement of these genes in Clostridium difficile and the life cycle of the bacterium in the host are markedly different from those of other pathogens. In the current work, we determined the contribution of the putative C. difficile dlt operon to CAMP resistance. Our data indicate that the dlt operon is necessary for full resistance of C. difficile to nisin, gallidermin, polymyxin B and vancomycin. We propose that the d-alanylation of teichoic acids provides protection against antimicrobial peptides that may be essential for growth of C. difficile in the host.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Shonna M
authors.initials: SM
authors.lastname: McBride
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Abraham L
authors.initials: AL
authors.lastname: Sonenshein
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016360:Clostridioides difficile / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D009876:Operon
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins