CpaA Is a Glycan-Specific Adamalysin-like Protease Secreted by Acinetobacter baumannii That Inactivates Coagulation Factor XII

Author:

Waack Ursula1,Warnock Mark2,Yee Andrew3,Huttinger Zachary3,Smith Sara1,Kumar Ayush4ORCID,Deroux Alban5,Ginsburg David36789,Mobley Harry L. T.1,Lawrence Daniel A.2,Sandkvist Maria1

Affiliation:

1. Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA

2. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA

3. Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA

4. Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada

5. Grenoble Alpes University Hospital, Grenoble, France

6. Howard Hughes Medical Institute, Ann Arbor, Michigan, USA

7. Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA

8. Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA

9. Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA

Abstract

Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii . Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo . Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro . We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII. We propose adding CpaA to a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Howard Hughes Medical Institute

U.S. Department of Defense

HHS | NIH | National Heart, Lung, and Blood Institute

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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