title: Moraxella catarrhalis expresses a cardiolipin synthase that impacts adherence to human epithelial cells.
abstract: The major phospholipid constituents of Moraxella catarrhalis membranes are phosphatidylglycerol, phosphatidylethanolamine, and cardiolipin (CL). However, very little is known regarding the synthesis and function of these phospholipids in M. catarrhalis. In this study, we discovered that M. catarrhalis expresses a cardiolipin synthase (CLS), termed MclS, that is responsible for the synthesis of CL within the bacterium. The nucleotide sequence of mclS is highly conserved among M. catarrhalis isolates and is predicted to encode a protein with significant amino acid similarity to the recently characterized YmdC/ClsC protein of Escherichia coli. Isogenic mclS mutant strains were generated in M. catarrhalis isolates O35E, O12E, and McGHS1 and contained no observable levels of CL. Site-directed mutagenesis of a highly conserved HKD motif of MclS also resulted in a CL-deficient strain. Moraxella catarrhalis, which depends on adherence to epithelial cells for colonization of the human host, displays significantly reduced levels of adherence to HEp-2 and A549 cell lines in the mclS mutant strains compared to wild-type bacteria. The reduction in adherence appears to be attributed to the absence of CL. These findings mark the first instance in which a CLS has been related to a virulence-associated trait.
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.
authors.forename: Sean W
authors.initials: SW
authors.lastname: Buskirk
authors.forename: Eric R
authors.initials: ER
authors.lastname: Lafontaine
mesh_terms: D001422:Bacterial Adhesion; D002308:Cardiolipins / Q000096:biosynthesis*; D002460:Cell Line; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004847:Epithelial Cells / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics; D017353:Gene Deletion; D022781:Hepatocytes / Q000382:microbiology; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D001936:Moraxella catarrhalis / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D017855:Transferases (Other Substituted Phosphate Groups) / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D002308:Cardiolipins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D017855:Transferases (Other Substituted Phosphate Groups); C100091:cardiolipin synthetase