Reactive nitrogen species (RNS) are a family of molecules including nitric oxide (NO) and peroxynitrite (ONOO) which are important constituents of most living organisms as they participate in a variety of physiological processes. However, they can be poisonous to certain cells due to their ability to disrupt a variety of essential biological processes.
Reactive nitrogen species (RNS) dilate blood vessels, regulate blood pressure, initiate immune responses, promote cellular growth, act as muscle relaxant, participate in signalling networks and orchestrate the execution of pathogens. The latter function is essentially restricted in the macrophages since elevated amounts of RNS are required to kill invading bacteria. In this instance, RNS interact with DNA, inactivate enzymes and arrest the energy-generating machinery of the microbial intruders.
In a review from Biological Chemistry, the authors 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
Yet, resistant microbes are known to devise intricate strategies to fend off the toxic influence of RNS. They neutralize the RNS and elaborate intricate metabolic pathways in order to survive. Since Adenosine triphosphate (ATP) production via aerobic respiration is severely impeded, RNS-resistant microbes utilize alternative energymaking machinery whereby oxygen is not required.
The ATP-synthesizing network is propelled by enzymes like citrate lyase, phosphoenol carboxylase, and phosphoenol diphosphate kinase. This molecular arrangement supplies a constant flow of ATP and ensures the survival of the resistant microbes.
The metabolic adaptation in these bacteria is immune to the RNS-killing machine and exposes important therapeutic targets. Drugs designed to inactivate the alternative ATP-synthesizing enzymes that are absent in humans may lead to an intriguing repertoire of medications aimed at microbes that are persistent despite the treatment with known antibiotics.
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