Peptidoglycan Recognition Proteins Kill Bacteria by Inducing Oxidative, Thiol, and Metal Stress

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Bacterial infections are still a major cause of morbidity and mortality because of increasing antibiotic resistance. New targets for developing new approaches to antibacterial therapy are needed, because discovering new or improving current antibiotics have become increasingly difficult. One such approach is developing new antibacterial agents based on the antibacterial mechanisms of bactericidal innate immunity proteins, such as human peptidoglycan recognition proteins (PGRPs). Thus, our aim was to determine how PGRPs kill bacteria. We previously proposed that PGRPs kill bacteria by inducing toxic oxygen by-products (“reactive oxygen species”, ROS) in bacteria. It was also previously proposed, but recently refuted, that bactericidal antibiotics kill bacteria by inducing ROS production in bacteria. These findings prompted us to evaluate in greater detail the mechanism of PGRP-induced bacterial killing, including the role of ROS in PGRP killing. We show here that PGRPs kill bacteria through synergistic induction of ROS, depletion of thiols, and increasing intracellular concentration of metals, which are all required, but individually not sufficient for bacterial killing. Our results reveal a novel bactericidal mechanism of innate immunity proteins, which differs from killing by antibiotics and offers alternative targets for developing new antibacterial therapies for antibiotic-resistant bacteria.

Vyšlo v časopise: Peptidoglycan Recognition Proteins Kill Bacteria by Inducing Oxidative, Thiol, and Metal Stress. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004280
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004280

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