Bioenergetics and Reactive Nitrogen Species in Bacteria

Borisov, Vitaliy B.; Forte, Elena

doi:10.3390/ijms23137321

Cited by 12 publications

(6 citation statements)

References 171 publications

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“…However, cyt bc 1 -aa 3 is not essential for cell survival and as long as the alternate cyt bd is expressed, bc 1 -aa 3 inhibitors do not induce bactericidal effects. The central role of the bc 1 -aa 3 complex in the ETC and the significant differences to the mammalian counterpart make the supercomplex a good therapeutical target [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ].…”

Section: Emerging Mtb Drug Targetsmentioning

confidence: 99%

Target Identification in Anti-Tuberculosis Drug Discovery

Capela

Félix

Clariano

et al. 2023

IJMS

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Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis (TB), a disease that, although preventable and curable, remains a global epidemic due to the emergence of resistance and a latent form responsible for a long period of treatment. Drug discovery in TB is a challenging task due to the heterogeneity of the disease, the emergence of resistance, and uncomplete knowledge of the pathophysiology of the disease. The limited permeability of the cell wall and the presence of multiple efflux pumps remain a major barrier to achieve effective intracellular drug accumulation. While the complete genome sequence of Mtb has been determined and several potential protein targets have been validated, the lack of adequate models for in vitro and in vivo studies is a limiting factor in TB drug discovery programs. In current therapeutic regimens, less than 0.5% of bacterial proteins are targeted during the biosynthesis of the cell wall and the energetic metabolism of two of the most important processes exploited for TB chemotherapeutics. This review provides an overview on the current challenges in TB drug discovery and emerging Mtb druggable proteins, and explains how chemical probes for protein profiling enabled the identification of new targets and biomarkers, paving the way to disruptive therapeutic regimens and diagnostic tools.

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Section: Emerging Mtb Drug Targetsmentioning

confidence: 99%

Target Identification in Anti-Tuberculosis Drug Discovery

Capela

Félix

Clariano

et al. 2023

IJMS

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“…NO is a diatomic free radical that is produced by the host immune system in response to bacterial infection. Exposure to NO and its congeners is both bactericidal and bacteriostatic, the effects being mediated through a range of well-known mechanisms, including modification of iron sulphur clusters [ 2 ], nitrosylation of thiol groups [ 3 ], nitration of tyrosine residues in the presence of superoxide [ 4 ], and through the inhibition of aerobic respiration via binding to haem cofactors of oxygen-dependent terminal oxidoreductases [ 5 ]. Bacteria can produce a variety of responses to NO [ 6 ], including systems involved in NO-detoxification, iron-sulphur (Fe-S) cluster repair, and the synthesis of NO-tolerant respiratory complexes such as cytochrome bd .…”

Section: No Is An Antimicrobial Respiratory Inhibitormentioning

confidence: 99%

The nitric oxide paradox: antimicrobial and inhibitor of antibiotic efficacy

Webster,

Shepherd

2023

Emerging Topics in Life Sciences

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It is well-known that antibiotics target energy-consuming processes and a significant body of research now supports the conclusion that the metabolic state of bacteria can have a profound impact upon the efficacy of antibiotics. Several articles implicate bacterial energetics and the respiratory inhibitor nitric oxide (NO) in this process, although pinpointing the precise mechanism for how NO can diminish the potency of a range of antibiotics through modulating bacterial energy metabolism has proved challenging. Herein, we introduce the role of NO during infection, consider known links between NO and antibiotic efficacy, and discuss potential mechanisms via which NO present at the site of infection could mediate these effects through controlling bacterial energetics. This perspective article highlights an important relationship between NO and antibiotic action that has largely been overlooked and outlines future considerations for the development of new drugs and therapies that target bacterial energy metabolism.

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“…A large body of evidence has demonstrated that bd -type oxidases, in addition to sustaining cell bioenergetics, can support virulence in several pathogens by providing protection against several stressors [ 25 ], including antibiotics [ 25 , 34 , 35 ], peroxynitrite [ 36 , 37 ], NO [ 38 , 39 ], hydrogen peroxide (H 2 O 2 ) [ 40 , 41 , 42 ], reactive oxygen species produced by macrophages, and H 2 S [ 43 ]. Significant sulfate concentrations and high H 2 S production have recently been reported in CF individuals infected by P. aeruginosa both at the site of infection and in the expectorate [ 44 , 45 ].…”

Section: Introductionmentioning

confidence: 99%

Cyanide Insensitive Oxidase Confers Hydrogen Sulfide and Nitric Oxide Tolerance to Pseudomonas aeruginosa Aerobic Respiration

Nastasi,

Caruso,

Giordano

et al. 2024

Antioxidants

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Hydrogen sulfide (H2S) and nitric oxide (NO) are long-known inhibitors of terminal oxidases in the respiratory chain. Yet, they exert pivotal signaling roles in physiological processes, and in several bacterial pathogens have been reported to confer resistance against oxidative stress, host immune responses, and antibiotics. Pseudomonas aeruginosa, an opportunistic pathogen causing life-threatening infections that are difficult to eradicate, has a highly branched respiratory chain including four terminal oxidases of the haem-copper type (aa3, cbb3-1, cbb3-2, and bo3) and one oxidase of the bd-type (cyanide-insensitive oxidase, CIO). As Escherichia coli bd-type oxidases have been shown to be H2S-insensitive and to readily recover their activity from NO inhibition, here we tested the effect of H2S and NO on CIO by performing oxygraphic measurements on membrane preparations from P. aeruginosa PAO1 and isogenic mutants depleted of CIO only or all other terminal oxidases except CIO. We show that O2 consumption by CIO is unaltered even in the presence of high levels of H2S, and that CIO expression is enhanced and supports bacterial growth under such stressful conditions. In addition, we report that CIO is reversibly inhibited by NO, while activity recovery after NO exhaustion is full and fast, suggesting a protective role of CIO under NO stress conditions. As P. aeruginosa is exposed to H2S and NO during infection, the tolerance of CIO towards these stressors agrees with the proposed role of CIO in P. aeruginosa virulence.

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Bioenergetics and Reactive Nitrogen Species in Bacteria

Cited by 12 publications

References 171 publications

Target Identification in Anti-Tuberculosis Drug Discovery

Target Identification in Anti-Tuberculosis Drug Discovery

The nitric oxide paradox: antimicrobial and inhibitor of antibiotic efficacy

Cyanide Insensitive Oxidase Confers Hydrogen Sulfide and Nitric Oxide Tolerance to Pseudomonas aeruginosa Aerobic Respiration

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