Outer membrane protein UspA1 and lipooligosaccharide are involved in invasion of human epithelial cells by Moraxella catarrhalis.
Invasion of non-professional phagocytes is a strategy employed by several mucosal pathogens, but has not been investigated in detail for Moraxella catarrhalis, a major cause of human respiratory tract infections. We investigated the role of outer membrane protein (OMP) UspA1 and lipooligosaccharide (LOS) in M. catarrhalis invasion into epithelial cells. An isogenic mutant of strain O35E, which lacked expression of the UspA1 adhesin, demonstrated not only severely impaired adherence (86%) to but also reduced invasion (77%) into Chang conjunctival cells in comparison with the wild-type strain. The isogenic, LOS-deficient mutant strain O35E.lpxA was attenuated in adherence (93%) and its capacity to invade was severely reduced (95%), but not abolished. Inhibition assays using sucrose and cytochalasin D, respectively, demonstrated that clathrin and actin polymerization contribute to internalization of M. catarrhalis by Chang cells. Furthermore, inhibition of UspA1-mediated binding to cell-associated fibronectin and alpha5beta1 integrin decreased invasion of M. catarrhalis strain O35E (72% and 41%, respectively). These data indicate that OMP UspA1 and LOS profoundly affect the capacity of M. catarrhalis to invade epithelial cells.
Spaniol
Violeta
V
Institute for Infectious Diseases, University of Bern, CH-3010 Bern, Switzerland.
Heiniger
Nadja
N
Troller
Rolf
R
Aebi
Christoph
C
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D001422:Bacterial Adhesion / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002966:Clathrin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015169:Colony Count, Microbial; D003600:Cytosol / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology*; D017353:Gene Deletion; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D001936:Moraxella catarrhalis / Q000235:genetics / Q000472:pathogenicity*; D016254:Mutagenesis, Insertional; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D001425:Bacterial Outer Membrane Proteins; D002966:Clathrin; D008070:Lipopolysaccharides; C089675:UspA protein, Moraxella catarrhalis; D037521:Virulence Factors; C023023:lipid-linked oligosaccharides