Novel Bacterial Inhibitor Blocks Lysozyme Activity in Model

A team of molecular microbiologists has identified a mechanism by which certain bacteria – in particular the Gram-negative pathogen Neisseria gonorrhoeae – avoid lysozyme destruction.

Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase is an antimicrobial enzyme produced by animals that forms part of the innate immune system. Lysozyme is a glycoside hydrolase that catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan, which is the major component of gram-positive bacterial cell wall. This hydrolysis in turn compromises the integrity of bacterial cell walls causing lysis of the bacteria.

Lysozymes are ubiquitous as the first line of immune defense against microbes in animals. They exert bactericidal action through antimicrobial peptide activity and peptidoglycan hydrolysis. Gram-negative bacteria developed several weapons to battle lysozymes, including inhibitors of c-type lysozymes in the MliC/PliC family and the Neisseria adhesin complex protein (ACP). Until the recent discovery of ACP, no proteinaceous lysozyme inhibitors were reported for the genus Neisseria, including the important human pathogen N. gonorrhoeae.

Investigators at Oregon State University (Corvallis, USA) have changed this picture. In a paper published in the July 5, 2018, online edition of the journal PLOS Pathogens, they described a previously unrecognized gonococcal virulence mechanism involving a protein encoded by the open reading frame ngo1063 that acted to counteract c-type lysozyme and provided a competitive advantage to the microorganism in a gonorrhea mouse model. They named this protein SliC for "surface-exposed lysozyme inhibitor of c-type lysozyme."

Although SliC displayed low overall primary sequence similarity to the MliC/PliC inhibitors, it was found to have a parallel inhibitory mechanism. The investigators showed that SliC was a surface-displayed lipoprotein in N. gonorrhoeae and, through its lysozyme-blocking function, played a critical role in colonization of genital tract mucosae during infection in the female gonorrhea mouse model.

"The infections very often are silent," said senior author Dr. Aleksandra Sikora, assistant professor of pharmacy at Oregon State University. "Up to 50% of infected women do not have symptoms, but those asymptomatic cases can still lead to some very severe consequences for the patient's reproductive health, miscarriage or premature delivery. This is the first time an animal model has been used to demonstrate a lysozyme inhibitor's role in gonorrhea infection. Together, all of our experiments show how important the lysozyme inhibitor is. This is very exciting."

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