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

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.

Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen

“…Data about enzymes in A. baumannii continue to culminate; recently, the enzyme CpaA, a glycan-specific adamalysin-like protease, was identified as a virulence factor that inhibits blood coagulation through inactivation of factor XII. As such, CpaA attenuates formation of thrombi in intravascular sites, promoting dissemination capacity of A. baumannii [74].…”

The UDP‐GalNAcA biosynthesis genes gna‐gne2 are required to maintain cell envelope integrity and in vivo fitness in multi‐drug resistant Acinetobacter baumannii

“…Until recently, just a subset of virulence factors had been identified, including capsule, lipooligosaccharide, metal acquisition systems (iron and zinc), secretion systems (Type I, II and VI), the phenotypic switch and a lytic transglycosylase (Wong et al, 2017;Chin et al, 2018;Crépin et al, 2018;Harding et al, 2018;Waack et al, 2018;Runci et al, 2019). However, the regulation of these factors and their specific roles in the pathobiology of A. baumannii infections are yet to be elucidated.…”

Acquisition of plasmids conferring carbapenem and aminoglycoside resistance and loss of surface-exposed macromolecule structures as strategies for the adaptation of Acinetobacter baumannii CC104O/CC15P strains to the clinical setting

“…(iii) CpaA. The cpaA gene encodes a metallopeptidase exhibiting the ability to cleave fibrinogen and coagulation factor XII, thus helping deregulate blood coagulation during infection [84]. CpaA, a substrate of the type-II secretion system, was thus proposed as a bona fide virulence factor [13,85].…”