Effect of different nitroheterocyclic compounds on aerobic, microaerophilic, and anaerobic bacteria

H, Hof; Ströder, J; Buisson, Jean‐Pierre; Royer, Robert E.

doi:10.1128/aac.30.5.679

Cited by 14 publications

(8 citation statements)

References 19 publications

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“…Metronidazole, a nitroimidazole derivative, is active against mizroaerophilic and anaerobic bacteria; although it has been reported that facultative anaerobic bacteria such as E. coli may respond to metronidazole, at least under strict anaerobic conditions (Hof et al, 1986). The drug is often Hung et al, 2007).…”

Section: Discussionmentioning

confidence: 97%

Antibiotic resistance pattern among the Salmonella isolated from human, animal and meat in India

Singh

Agarwal

Tiwari

et al. 2011

Trop Anim Health Prod

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The present study was conducted to study the antibiotic resistance pattern among nontyphoidal Salmonella isolated from human, animal and meat. A total of 37 Salmonella strains isolated from clinical cases (human and animal) and meat during 2008-2009 belonging to 12 serovars were screened for their antimicrobial resistance pattern using 25 antimicrobial agents falling under 12 different antibiotic classes. All the Salmonella isolates tested showed multiple drug resistance varying from 5.40% to 100% with 16 of the 25 antibiotics tested. None of the isolates were sensitive to erythromycin and metronidazole. Resistance was also observed against clindamycin (94.59%), ampicillin (86.49%), co-trimoxazole (48.65%), colistin (45.94%), nalidixic acid (35.10%), amoxyclave (18.90%), cephalexin, meropenem, tobramycin, nitrofurantoin, tetracycline, amoxicillin (8.10% each), sparfloxacin and streptomycin (5.40% each). Isolates from clinical cases of animals were resistant to as many as 16 antibiotics, whereas isolates from human clinical cases and meat were resistant to 9 and 14 antibiotics, respectively. Overall, 19 resistotypes were recorded. Analysis of multiple antibiotic resistance index (MARI) indicated that clinical isolates from animals had higher MARI (0.25) as compared to isolates from food (0.22) and human (0.21). Among the different serotypes studied for antibiogram, Paratyhi B isolates, showed resistance to three to 13 antibiotics, whereas Typhimurium strains were resistant to four to seven antibiotics. Widespread multidrug resistance among the isolates from human, animal and meat was observed. Some of the uncommon serotypes exhibited higher resistance rate. Considerable changes in the resistance pattern were also noted. An interesting finding was the reemergence of sensitivity to some of the old antibiotics (chloromphenicol, tetracycline).

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Section: Discussionmentioning

confidence: 97%

Antibiotic resistance pattern among the Salmonella isolated from human, animal and meat in India

Singh

Agarwal

Tiwari

et al. 2011

Trop Anim Health Prod

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“…Mechanism of action of NTZ and nitrofurans. The antimicrobial action of nitrofurans, nitrothiazoles, and nitroimidazoles is generally believed to result from a 4-electron reduction of the 5-nitro group to short-lived redox active intermediates, including hydroxylamine adducts that are biologically active (7,12,22). We had found that MTZ reduction leads to transversion and transition base mutations and sufficient DNA fragmentation to cause lethality (29).…”

Section: Discussionmentioning

confidence: 99%

“…These considerations have stimulated interest in alternative redox-active prodrugs in either first-line or salvage (failed eradication) therapies, especially those against which resistance may be uncommon in H. pylori. Alternative prodrugs include the nitrofurans and nitrothiazoles, which exhibit antimicrobial activity against H. pylori and also against facultative anaerobes, anaerobic bacterial and protozoan species, and helminths (12,19,21,30,32,33). For these drugs, the spectrum of bioactivity and the mechanisms of activation are largely a function of the redox potential (EЈ 7 ) of the 5-nitro groups.…”

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confidence: 99%

Enzymes Associated with Reductive Activation and Action of Nitazoxanide, Nitrofurans, and Metronidazole in Helicobacter pylori

Sisson¹,

Goodwin

Raudonikiene³

et al. 2002

Antimicrob Agents Chemother

158

170

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Nitazoxanide (NTZ) is a redox-active nitrothiazolyl-salicylamide prodrug that kills Helicobacter pylori and also many anaerobic bacterial, protozoan, and helminthic species. Here we describe development and use of a spectrophotometric assay, based on nitroreduction of NTZ at 412 nm, to identify H. pylori enzymes responsible for its activation and mode of action. Three enzymes that reduce NTZ were identified: two related NADPH nitroreductases, which also mediate susceptibility to metronidazole (MTZ) (RdxA and FrxA), and pyruvate oxidoreductase (POR). Recombinant His-tagged RdxA, FrxA, and POR, overexpressed in nitroreductasedeficient Escherichia coli, each rapidly reduced NTZ, whereas only FrxA and to a lesser extent POR reduced nitrofuran substrates (furazolidone, nitrofurantoin, and nitrofurazone). POR exhibited no MTZ reductase activity either in extracts of H. pylori or following overexpression in E. coli; RdxA exhibited no nitrofuran reductase activity, and FrxA exhibited no MTZ reductase activity. Analysis of mutation to rifampin resistance (Rif r ) indicated that NTZ was not mutagenic and that nitrofurans were only weakly mutagenic. Alkaline gel DNA electrophoresis indicated that none of these prodrugs caused DNA breakage. In contrast, MTZ caused DNA damage and was strongly mutagenic. We conclude that POR, an essential enzyme, is responsible for most or all of the bactericidal effects of NTZ against H. pylori. While loss-of-function mutations in rdxA and frxA produce a Mtz r phenotype, they do not contribute much to the innate susceptibility of H. pylori to NTZ or nitrofurans.Prodrugs are particularly appealing as therapeutic agents because of their selective toxicity for microorganisms possessing specific activating enzymes (7). Metronidazole (MTZ) is a nitroimidazole prodrug that is often used in combination therapies against Helicobacter pylori, the microaerobic bacterium that causes gastritis and peptic ulcer disease and that is an early risk factor for gastric cancer (6,19,30). However, resistance to MTZ is very common and reduces the efficacy of MTZ-containing regimes (10). MTZ is also highly mutagenic, and hence its use may accelerate development of resistance to other clinically important antibiotics, such as clarithromycin (24,29). These considerations have stimulated interest in alternative redox-active prodrugs in either first-line or salvage (failed eradication) therapies, especially those against which resistance may be uncommon in H. pylori. Alternative prodrugs include the nitrofurans and nitrothiazoles, which exhibit antimicrobial activity against H. pylori and also against facultative anaerobes, anaerobic bacterial and protozoan species, and helminths (12,19,21,30,32,33). For these drugs, the spectrum of bioactivity and the mechanisms of activation are largely a function of the redox potential (EЈ 7 ) of the 5-nitro groups. For example, nitrofurans (nitrofurazone, nitrofurantoin, and furazolidone) display relatively high redox potentials (Ϫ250 to Ϫ270 mV) and are reductively activated by a...

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“…In this subsection, we will address the cases with evidence and, preferentially, quantitative demonstration of the contribution of reductive processes to the action of ArNO 2 . Nitroreductase-deficient mutants of E. coli were resistant to all types of nitroaromatic compounds [281,282]. This points to the principal role of NRs in their bioactivation.…”

Section: Role Of Bioreductive Processes In Antibacterial and Antiparasitic Action Of Nitroaromaticsmentioning

confidence: 99%

Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity

Čėnas

Nemeikaitė-Čėnienė

Kosychova

2021

IJMS

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Nitroaromatic compounds (ArNO2) maintain their importance in relation to industrial processes, environmental pollution, and pharmaceutical application. The manifestation of toxicity/therapeutic action of nitroaromatics may involve their single- or two-electron reduction performed by various flavoenzymes and/or their physiological redox partners, metalloproteins. The pivotal and still incompletely resolved questions in this area are the identification and characterization of the specific enzymes that are involved in the bioreduction of ArNO2 and the establishment of their contribution to cytotoxic/therapeutic action of nitroaromatics. This review addresses the following topics: (i) the intrinsic redox properties of ArNO2, in particular, the energetics of their single- and two-electron reduction in aqueous medium; (ii) the mechanisms and structure-activity relationships of reduction in ArNO2 by flavoenzymes of different groups, dehydrogenases-electrontransferases (NADPH:cytochrome P-450 reductase, ferredoxin:NADP(H) oxidoreductase and their analogs), mammalian NAD(P)H:quinone oxidoreductase, bacterial nitroreductases, and disulfide reductases of different origin (glutathione, trypanothione, and thioredoxin reductases, lipoamide dehydrogenase), and (iii) the relationships between the enzymatic reactivity of compounds and their activity in mammalian cells, bacteria, and parasites.

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Effect of different nitroheterocyclic compounds on aerobic, microaerophilic, and anaerobic bacteria

Abstract: The antibacterial activities of different nitroheterocyclic compounds were assessed by an agar dilution method against aerobic, microaerophilic, and anaerobic bacteria. Nitronaphthofurans inhibited the multipli-

Cited by 14 publications

References 19 publications

Antibiotic resistance pattern among the Salmonella isolated from human, animal and meat in India

Antibiotic resistance pattern among the Salmonella isolated from human, animal and meat in India

Enzymes Associated with Reductive Activation and Action of Nitazoxanide, Nitrofurans, and Metronidazole in Helicobacter pylori

Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity

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