Pseudomonas aeruginosa defense systems against microbicidal oxidants.

Abstract:

:The most abundant oxidants controlling bacterial colonization on mucosal barrier epithelia are hypochlorous acid (HOCl), hypobromous acid (HOBr) and hypothiocyanous acid (HOSCN). All three oxidants are highly antimicrobial but little is known about their relative efficacies, their respective cellular targets, or what specific responses they elicit in bacteria. To address these important questions, we directly tested the individual oxidants on the virulent Pseudomonas aeruginosa strain PA14. We discovered that HOCl and HOBr work almost interchangeably, impacting non-growing bacterial cultures more significantly than actively growing bacteria, and eliciting similar stress responses, including the heat shock response. HOSCN treatment is distinctly different, affecting primarily actively growing PA14 and evoking stress responses suggestive of membrane damage. What all three oxidants have in common, however, is their ability to cause substantial protein aggregation. This effect became particularly obvious in strains lacking polyphosphate, a newly recognized chemical chaperone. Treatment of PA14 with the FDA-approved anti-inflammatory drug mesalamine, which has recently been shown to attenuate polyP production in a wide range of bacteria, effectively decreased the resistance of PA14 toward all three oxidants, suggesting that we have discovered a novel, targetable defense system in P. aeruginosa.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Groitl B,Dahl JU,Schroeder JW,Jakob U

doi

10.1111/mmi.13768

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

335-350

issue

3

eissn

0950-382X

issn

1365-2958

journal_volume

106

pub_type

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