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Moraxella-Dependent ₁-Antichymotrypsin Neutralization

A Unique Virulence Mechanism

¹ Medical Microbiology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, Malmö, Sweden; and ² Department of Internal Medicine, Singapore General Hospital, Singapore

Correspondence and reprint requests should be addressed to Kristian Riesbeck, MD, PhD, Medical Microbiology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, SE-205 02 Malmö, Sweden. E-mail: kristian.riesbeck{at}med.lu.se

The acute phase reactant and protease inhibitor 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.

Key Words: bacteria • inflammation • protease inhibitor

CLINICAL RELEVANCE 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.