There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

ABSTRACT Reactive chlorine species (RCS) defense mechanisms are important for bacterial fitness in diverse environments. In addition to the anthropogenic use of RCS in the form of bleach, these compounds are also produced naturally through photochemical reactions of natural organic matter and in vivo by the mammalian immune system in response to invading microorganisms. To gain insight into bacterial RCS defense mechanisms, we investigated Azospira suillum strain PS, which produces periplasmic RCS as an intermediate of perchlorate respiration. Our studies identified an RCS response involving an RCS stress-sensing sigma/anti-sigma factor system (SigF/NrsF), a soluble hypochlorite-scavenging methionine-rich periplasmic protein (MrpX), and a putative periplasmic methionine sulfoxide reductase (YedY1). We investigated the underlying mechanism by phenotypic characterization of appropriate gene deletions, chemogenomic profiling of barcoded transposon pools, transcriptome sequencing, and biochemical assessment of methionine oxidation. Our results demonstrated that SigF was specifically activated by RCS and initiated the transcription of a small regulon centering around yedY1 and mrpX. A yedY1 paralog (yedY2) was found to have a similar fitness to yedY1 despite not being regulated by SigF. Markerless deletions of yedY2 confirmed its synergy with the SigF regulon. MrpX was strongly induced and rapidly oxidized by RCS, especially hypochlorite. Our results suggest a mechanism involving hypochlorite scavenging by sacrificial oxidation of the MrpX in the periplasm. Reduced MrpX is regenerated by the YedY methionine sulfoxide reductase activity. The phylogenomic distribution of this system revealed conservation in several Proteobacteria of clinical importance, including uropathogenic Escherichia coli and Brucella spp., implying a putative role in immune response evasion in vivo.

Related collections

Most cited references 31

Record: found
Abstract: found
Article: not found

The third pillar of bacterial signal transduction: classification of the extracytoplasmic function (ECF) sigma factor protein family.

Anna Nagy-Staroń, Heidi J Sofia, Sascha Dietrich … (2009)

The ability of a bacterial cell to monitor and adaptively respond to its environment is crucial for survival. After one- and two-component systems, extracytoplasmic function (ECF) sigma factors - the largest group of alternative sigma factors - represent the third fundamental mechanism of bacterial signal transduction, with about six such regulators on average per bacterial genome. Together with their cognate anti-sigma factors, they represent a highly modular design that primarily facilitates transmembrane signal transduction. A comprehensive analysis of the ECF sigma factor protein family identified more than 40 distinct major groups of ECF sigma factors. The functional relevance of this classification is supported by the sequence similarity and domain architecture of cognate anti-sigma factors, genomic context conservation, and potential target promoter motifs. Moreover, this phylogenetic analysis revealed unique features indicating novel mechanisms of ECF-mediated signal transduction. This classification, together with the web tool ECFfinder and the information stored in the Microbial Signal Transduction (MiST) database, provides a comprehensive resource for the analysis of ECF sigma factor-dependent gene regulation.

0 comments Cited 150 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Absolute rate constants for the reaction of hypochlorous acid with protein side chains and peptide bonds.

D Pattison, Q Davies (2001)

Hypochlorous acid (HOCl) is a potent oxidant, which is produced in vivo by activated phagocytes. This compound is an important antibacterial agent, but excessive or misplaced production has been implicated in a number of human diseases, including atherosclerosis, arthritis, and some cancers. Proteins are major targets for this oxidant, and such reaction results in side-chain modification, backbone fragmentation, and cross-linking. Despite a wealth of qualitative data for such reactions, little absolute kinetic data is available to rationalize the in vitro and in vivo data. In this study, absolute second-order rate constants for the reactions of HOCl with protein side chains, model compounds, and backbone amide (peptide) bonds have been determined at physiological pH values. The reactivity of HOCl with potential reactive sites in proteins is summarized by the series: Met (3.8 x 10(7) M(-1) x s(-1)) > Cys (3.0 x 10(7) M(-1) x s(-1)) > cystine (1.6 x 10(5) M(-1) x s(-1)) approximately His (1.0 x 10(5) M(-1) x s(-1)) approximately alpha-amino (1.0 x 10(5) M(-1) x s(-1)) > Trp (1.1 x 10(4) M(-1) x s(-1)) > Lys (5.0 x 10(3) M(-1) x s(-1)) > Tyr (44 M(-1) x s(-1)) approximately Arg (26 M(-1) x s(-1)) > backbone amides (10-10(-3) M(-1) x s(-1)) > Gln(0.03 M(-1) x s(-1)) approximately Asn (0.03 M(-1) x s(-1)). The rate constants for reaction of HOCl with backbone amides (peptide bonds) vary by 4 orders of magnitude with uncharged peptide bonds reacting more readily with HOCl than those in a charged environment. These kinetic parameters have been used in computer modeling of the reactions of HOCl with human serum albumin, apolipoprotein-A1 and free amino acids in plasma at different molar excesses. These models are useful tools for predicting, and reconciling, experimental data obtained in HOCl-induced oxidations and allow estimations to be made as to the flux of HOCl to which proteins are exposed in vivo.