Reactive nitrogen species (RNS)-resistant microbes: adaptation and medical implications.

Abstract:

:Nitrosative stress results from an increase in reactive nitrogen species (RNS) within the cell. Though the RNS - nitric oxide (·NO) and peroxynitrite (ONOO-) - play pivotal physiological roles, at elevated concentrations, these moieties can be poisonous to both prokaryotic and eukaryotic cells alike due to their capacity to disrupt a variety of essential biological processes. Numerous microbes are known to adapt to nitrosative stress by elaborating intricate strategies aimed at neutralizing RNS. In this review, we will discuss both the enzymatic systems dedicated to the elimination of RNS as well as the metabolic networks that are tailored to generate RNS-detoxifying metabolites - α-keto-acids. The latter has been demonstrated to nullify RNS via non-enzymatic decarboxylation resulting in the production of a carboxylic acid, many of which are potent signaling molecules. Furthermore, as aerobic energy production is severely impeded during nitrosative stress, alternative ATP-generating modules will be explored. To that end, a holistic understanding of the molecular adaptation to nitrosative stress, reinforces the notion that neutralization of toxicants necessitates significant metabolic reconfiguration to facilitate cell survival. As the alarming rise in antimicrobial resistant pathogens continues unabated, this review will also discuss the potential for developing therapies that target the alternative ATP-generating machinery of bacteria.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Tharmalingam S,Alhasawi A,Appanna VP,Lemire J,Appanna VD

doi

10.1515/hsz-2017-0152

subject

Has Abstract

pub_date

2017-10-26 00:00:00

pages

1193-1208

issue

11

eissn

1431-6730

issn

1437-4315

pii

/j/bchm.just-accepted/hsz-2017-0152/hsz-2017-0152.

journal_volume

398

pub_type

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