When a popular industrial enzyme promotes bacterial virulence

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The discovery of Lytic Polysaccharide Monooxygenases (LPMOs) in 2010 (1) received considerable attention and made a large impact in the field of biomass degradation due to their importance in the enzymatic conversion of chitin and cellulose. Prior to then the canonical enzymatic machineries involved in degradation of recalcitrant polysaccharides mostly contained hydrolytic enzymes. LPMOs revolutionized design of industrial enzyme cocktails, as these unique copper-containing redox enzymes employ powerful oxidative chemistry to cleave the glycosidic bonds of polysaccharides and work in synergy with glycoside hydrolases.

How are LPMOs connected to bacterial pathogenesis? These proteins were formerly considered “chitin binding proteins” (CBPs) as several contained auxiliary chitin-binding domains. “CBP” encoding genes were found in numerous bacterial genomes and while their function was unknown, a role in chitin catabolism rather than pathogenesis was suspected. However, several intriguing -omics analyses reported their upregulation upon interaction with host components such as blood, urine or sputum, providing a potential linkage to virulence (reviewed in 2). Indeed, prior to its recognition as an enzymatically functional LPMO, Vibrio cholerae GbpA was implicated in host colonization (3).

 Encouraged by these hints in the literature, we launched a project in 2018 to unravel the role of LPMOs in pathogenesis, placing our top priority on the multidrug-resistant opportunistic human pathogen Pseudomonas aeruginosa. The LPMO expressed by P. aeruginosa is called “chitin-binding protein D” (CbpD), and data suggesting it could play a role in virulence were so far circumstantial. We employed our complementary expertise in wet- and dry-lab technology in an interdisciplinary manner to explore the molecular determinants of this unique copper-dependent redox enzyme that impact colonization vs. invasive infection by P. aeruginosa. In our study, we show that secreted CbpD indeed is a catalytically competent LPMO that provides a strong pathogenicity phenotype and proteome re-organization in the context of systemic infection. Thus, LPMO function is not restricted to polysaccharide degradation, and our in-depth functional analyses revealed CbpD to attenuate the lytic mechanism of complement, allowing the pathogen to resist innate immune clearance in blood. Orthologs of CbpD are found in many Gram-negative and Gram-positive pathogens, including Vibrio cholerae and Enterococcus faecium, suggesting a potential common function of LPMOs in bacterial immune evasion.

 The prospect of effective solutions to counter the expanding antimicrobial resistance crisis has increasingly fallen on innovative basic and translational research. Given the particular importance of CbpD for P. aeruginosa, these proteins may be considered promising vaccine antigens or targets for combating infections through the emerging concept anti-virulence therapeutics.  By rendering the organism more sensitive to complement clearance, the potential may exist to treat P. aeruginosa with reduced antibiotic pressure for resistance evolution and less collateral damage to the healthy microbiota.  


1. Vaaje-Kolstad, G. et al. An oxidative enzyme boosting the enzymatic conversion of recalcitrant polysaccharides. Science 330, 219-222, doi:10.1126/science.1192231 (2010).

2. Agostoni, M., Hangasky, J. A. & Marletta, M. A. Physiological and molecular understanding of bacterial polysaccharide monooxygenases. Microbiol Mol Biol R 81, doi:10.1128/MMBR.00015-17 (2017).

3. Kirn, T. J., Jude, B. A. & Taylor, R. K. A colonization factor links Vibrio cholerae environmental survival and human infection. Nature 438, 863-866, doi:10.1038/nature04249 (2005).


Fatemeh Askarian

Postdoctoral in Bacterial Pathogenesis, Norwegian University of Life Sciences