title: Moraxella-dependent alpha 1-antichymotrypsin neutralization: a unique virulence mechanism.
abstract: The acute phase reactant and protease inhibitor alpha(1)-antichymotrypsin is considered to play a protective role in the airways, but whether it interacts with respiratory bacteria is not known. We analyzed whether the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and other bacterial species interact with antichymotrypsin. M. catarrhalis was the only species that bound antichymotrypsin among 25 bacterial species tested by flow cytometry and direct binding assay. We compared a series of clinical isolates in addition to wild-type and ubiquitous surface protein-deficient Moraxella to study the nature of antichymotrypsin binding by the bacteria. Experiments with Moraxella mutants revealed that ubiquitous surface proteins A1 and A2 were responsible for the interaction, and using recombinant fragments, a consensus sequence within ubiquitous surface proteins A1 and A2 was defined. Binding of iodine-labeled antichymotrypsin was dose dependent and strong (dissociation constant [K(d)] 24.9-44.8 nM). Moreover, a chymotrypsin activity assay showed that antichymotrypsin, when bound to the bacterial surface, was neutralized. Moraxella antichymotrypsin neutralization is a novel microbial virulence mechanism that may induce excessive inflammation resulting in more exposed extracellular matrix that is beneficial for bacterial colonization.
authors: Medical Microbiology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, SE-205 02 Malmö, Sweden.
authors: Taras
authors: T
authors: Manolov
authors: Thuan Tong
authors: TT
authors: Tan
authors: Arne
authors: A
authors: Forsgren
authors: Kristian
authors: K
authors: Riesbeck
mesh_terms: D000595:Amino Acid Sequence; D001422:Bacterial Adhesion / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000502:physiology; D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000382:microbiology; D002469:Cell Separation; D005434:Flow Cytometry; D006193:Haemophilus influenzae / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D001936:Moraxella catarrhalis / Q000235:genetics / Q000472:pathogenicity*; D045828:Moraxellaceae Infections / Q000378:metabolism / Q000382:microbiology; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; C089675:UspA protein, Moraxella catarrhalis; D000514:alpha 1-Antichymotrypsin