What is it about?

Lytic polysaccharide monooxygenases (LPMOs) are oxidative enzymes that use electrons together with oxygen or peroxide to dissolve chemical bonds and break down long carbohydrate chains such as cellulose found in plants or chitin found in crab shells. Recently, UC San Diego (UCSD) researchers collaborated with colleagues in Norway to show that an LPMO enzyme produced by the leading human bacterial pathogen, Pseudomonas aeruginosa, can protect against lethal pneumonia and sepsis in mice when used as a vaccine antigen. The research findings are published online this week in the Proceedings of the National Academy of Sciences (PNAS).

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Why is it important?

The discovery of LPMOs in 2010 launched a new field within carbohydrate biochemistry and created intensive study devoted to potential industrial applications in biomass conversion. However, a 2019 paper spearheaded by Fatemeh Askarian, PhD, UC San Diego Assistant Project Scientist in the UCSD Department of Pediatrics, showed that P. aeruginosa produced an LPMO, called chitin binding protein D (CbpD), that was required for it to produce disease in experimental mouse models. This unexpected and intriguing finding held medical significance, since P. aeruginosa causes serious and sometimes life-threatening infections in hospitalized or immunocompromised patients, including those with cystic fibrosis lung disease or undergoing cancer chemotherapy.

Perspectives

These results inspired Dr. Askarian and other team members in the laboratory of Victor Nizet, MD, UC San Diego Distinguished Professor of Pediatrics and Pharmacy, to explore whether the CpbD protein could be purified and used as a vaccine antigen for defense against serious P. aeruginosa infection. The new PNAS manuscript describes how X-ray crystallography and machine learning algorithms allowed structure-based mapping of the optimal immune epitopes for vaccine performance, and how full length CbpD protein and certain of its domains could be used to immunize mice and protect them against lethal pneumonia or sepsis. The research demonstrates that CbpD helps P. aeruginosa to avoid clearance from lung tissues and the blood, but that stimulating the production of antibodies to neutralize CbpD helps the host immune system regain the upper hand. Since LPMOs are found in several additional important human bacterial pathogens, the UC San Diego researchers are expanding their study of these curious enzymes in host-pathogen interactions and as potential therapeutic targets.

Victor Nizet
University of California San Diego

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This page is a summary of: Immunization with lytic polysaccharide monooxygenase CbpD induces protective immunity against Pseudomonas aeruginosa pneumonia, Proceedings of the National Academy of Sciences, July 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2301538120.
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