AUTHOR=da Cruz Nizer Waleska Stephanie , Adams Madison Elisabeth , Inkovskiy Vasily , Beaulieu Carole , Overhage Joerg 

TITLE=The secondary metabolite hydrogen cyanide protects Pseudomonas aeruginosa against sodium hypochlorite-induced oxidative stress

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1294518

DOI=10.3389/fmicb.2023.1294518

ISSN=1664-302X

ABSTRACT=<p>The high pathogenicity of <italic>Pseudomonas aeruginosa</italic> is attributed to the production of many virulence factors and its resistance to several antimicrobials. Among them, sodium hypochlorite (NaOCl) is a widely used disinfectant due to its strong antimicrobial effect. However, bacteria develop many mechanisms to survive the damage caused by this agent. Therefore, this study aimed to identify novel mechanisms employed by <italic>P. aeruginosa</italic> to resist oxidative stress induced by the strong oxidizing agent NaOCl. We analyzed the growth of the <italic>P. aeruginosa</italic> mutants Δ<italic>katA</italic>, Δ<italic>katE</italic>, Δ<italic>ahpC</italic>, Δ<italic>ahpF</italic>, Δ<italic>msrA</italic> at 1 μg/mL NaOCl, and showed that these known H<sub>2</sub>O<sub>2</sub> resistance mechanisms are also important for the survival of <italic>P. aeruginosa</italic> under NaOCl stress. We then conducted a screening of the <italic>P. aeruginosa</italic> PA14 transposon insertion mutant library and identified 48 mutants with increased susceptibility toward NaOCl. Among them were 10 mutants with a disrupted <italic>nrdJa, bvlR, hcnA, orn, sucC, cysZ, nuoJ,</italic> PA4166, <italic>opmQ,</italic> or <italic>thiC</italic> gene, which also exhibited a significant growth defect in the presence of NaOCl. We focussed our follow-up experiments (i.e., growth analyzes and kill-kinetics) on mutants with defect in the synthesis of the secondary metabolite hydrogen cyanide (HCN). We showed that HCN produced by <italic>P. aeruginosa</italic> contributes to its resistance toward NaOCl as it acts as a scavenger molecule, quenching the toxic effects of NaOCl.</p>