Molecular Characterization of Nitroimidazole Resistance in Metronidazole-Resistant &lt;i&gt;Bacteroides&lt;/i&gt; Species Isolated from Hospital Patients in Kuwait

Jamal, Wafaa; Rotimi, Vincent O.; Brazier, Jon S.; Johny, Molly; Wetieh, Wafaa M.; Duerden, B. I.

doi:10.1159/000076954

Cited by 15 publications

(12 citation statements)

References 29 publications

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“…Soki J et al 26 , Stubbs et al 27 , Trinhs and Reysset et al 28 . Jamal W Y et al 29 had shown Metronidazole resistant Bacteroides fragilis which are in support of our study.…”

Section: Discussionsupporting

confidence: 91%

“…Thus maximum recovery of Bacteroides fragilis isolates were from pus (21%), and less number of isolates were from blood and aspirates. Table 4 (Chart 3) shows that out of the total 32 isolates, 14 (8%) were isolated from post-operative wound infections, 11 (6.2%) isolated from diabetic foot ulcers, 2 (1.1%) isolates were from wound infections following Burns, 2 (1.1%) were from open injury following accidents, 1 (0.5%) was isolated from decubitus ulcers, septicaemia and intra-abdominal 29 (90.7%) susceptible and 3 (9.3%) resistant for tetracycline. Thus, it was found that only one organism was resistant for metronidazole and chloramphenicol, i.e.…”

Section: Resultsmentioning

confidence: 99%

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Bacteroides Fragilis in Sepsis

Chandrasegaran¹

2016

jemds

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PURPOSE1. To find out the prevalence of Bacteroides fragilis in patients with Sepsis and to perform Antimicrobial susceptibility testing. 2. To identify the Metronidazole resistant Bacteroides fragilis and to confirm the resistant pattern genomically by gene sequencing. MATERIALS AND METHODSThis prospective study was conducted for 6 months in 175 patients with varied infections. The presumptive identification of Bacteroides fragilis was confirmed and Antimicrobial susceptibility testing was performed by Broth disc method described by Kurynski & Co-workers. Resistant strains confirmed by short sequencing by NCBI Blast. RESULTSBacteroides fragilis was isolated from 32 of 175 samples with a prevalence of 18.3%. Out of this 32 samples, only one organism revealed resistance to Metronidazole. CONCLUSIONThe prevalence of Bacteroides fragilis resistant to metronidazole was isolated in post-operative wound infections giving a warning signal to the clinicians on emerging Metronidazole resistance on nosocomial infections in this hospital.

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“…Soki J et al 26 , Stubbs et al 27 , Trinhs and Reysset et al 28 . Jamal W Y et al 29 had shown Metronidazole resistant Bacteroides fragilis which are in support of our study.…”

Section: Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Bacteroides Fragilis in Sepsis

Chandrasegaran¹

2016

jemds

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“…More importantly, because of its unstable nature on mobilizable plasmids, Nim gene-based resistance poses a real threat to the existing applications of 5-Ni drugs. Indeed, a recent study identified seven Bacteroides-resistant strains with minimum inhibitory concentrations of Ͼ32 g/ml, all containing Nim genes (23).…”

Section: Dimetridazole (Dmz) and Tinidazole (Tnz) Mtr Is Extensivelmentioning

confidence: 99%

Structural Basis of 5-Nitroimidazole Antibiotic Resistance

Leiros¹,

Kozielski-Stuhrmann²,

Kapp

et al. 2004

Journal of Biological Chemistry

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5-Nitroimidazole-based antibiotics are compounds extensively used for treating infections in humans and animals caused by several important pathogens. They are administered as prodrugs, and their activation depends upon an anaerobic 1-electron reduction of the nitro group by a reduction pathway in the cells. Bacterial resistance toward these drugs is thought to be caused by decreased drug uptake and/or an altered reduction efficiency. One class of resistant strains, identified in Bacteroides, has been shown to carry Nim genes (NimA, -B, -C, -D, and -E), which encode for reductases that convert the nitro group on the antibiotic into a non-bactericidal amine. In this paper, we have described the crystal structure of NimA from Deinococcus radiodurans (drNimA) at 1.6 Å resolution. We have shown that drNimA is a homodimer in which each monomer adopts a ␤-barrel fold. We have identified the catalytically important His-71 along with the cofactor pyruvate and antibiotic binding sites, all of which are found at the monomer-monomer interface. We have reported three additional crystal structures of drNimA, one in which the antibiotic metronidazole is bound to the protein, one with pyruvate covalently bound to His-71, and one with lactate covalently bound to His-71. Based on these structures, a reaction mechanism has been proposed in which the 2-electron reduction of the antibiotic prevents accumulation of the toxic nitro radical. This mechanism suggests that Nim proteins form a new class of reductases, conferring resistance against 5-nitroimidazole-based antibiotics.Antibiotic resistance is an increasing problem throughout the developed world, and knowledge about different resistance mechanisms is important for efficient treatment of bacterial infections. One important class of antibiotics, the 5-nitroimidazole (5-Ni) 1 drug derivatives, includes metronidazole (MTR), dimetridazole (DMZ), and tinidazole (TNZ). MTR is extensively used in the treatment of anaerobic infections caused by Trichomonas vaginalis, Entamoeba histolytica, Enterococcus species, Giardia lamblia, Clostridium species, and Bacteroides (1-4) and is also a critical ingredient of modern multidrug therapies for Helicobacter pylori eradication regimes used to control ulcers (5). The mode of action for the 5-Ni antibiotics, as illustrated in Fig. 1, has been shown to be similar in different pathogens (6 -8). The inactive prodrug enters cells by simple diffusion and is then reduced in a 1-electron reduction into the toxic compound, the short-lived radical anion R-N⅐O 2 Ϫ . This reaction is mediated by ferredoxin, which receives an electron from the pyruvate-ferredoxin oxidoreductase (PFOR) complex via conversion of pyruvate to acetyl coenzyme A (9). The resulting nitro radical anion probably causes DNA strand breaks, DNA helix destabilization, unwinding of DNA, and finally cell death (1, 2, 10, 11), and damage to other vital cell systems is also possible (6).The success of such drugs depends on the reductive activation of the nitro group on the 5-Ni drug, which ...

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“…Four of the nim genes are associated with mobile insertion-sequence (IS) elements, posing a threat to the existing applications of 5-Ni drugs. Indeed, one study identified seven resistant Bacteroides strains with minimum inhibitory concentrations of >32 mg ml À1 , all of which contained nim genes (Jamal et al, 2004). Even if the rate of 5-Ni resistance is still low, organisms with metronidazole resistance are beginning to emerge (Haggoud et al, 1994;Lö fmark et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

High-resolution structure of the antibiotic resistance protein NimA fromDeinococcus radiodurans

2008

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Many anaerobic human pathogenic bacteria are treated using 5-nitroimidazole-based (5-Ni) antibiotics, a class of inactive prodrugs that contain a nitro group. The nitro group must be activated in an anaerobic one-electron reduction and is therefore dependent on the redox system in the target cells. Antibiotic resistance towards 5-Ni drugs is found to be related to the nim genes (nimA, nimB, nimC, nimD, nimE and nimF), which are proposed to encode a reductase that is responsible for converting the nitro group of the antibiotic into a nonbactericidal amine. A mechanism for the Nim enzyme has been proposed in which two-electron reduction of the nitro group leads to the generation of nontoxic derivatives and confers resistance against these antibiotics. The cofactor was found to be important in the mechanism and was found to be covalently linked to the reactive His71. In this paper, the 1.2 A atomic resolution crystal structure of the 5-nitroimidazole antibiotic resistance protein NimA from Deinococcus radiodurans (DrNimA) is presented. A planar cofactor is clearly visible and well defined in the electron-density map adjacent to His71, the identification of the cofactor and its properties are discussed.

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Molecular Characterization of Nitroimidazole Resistance in Metronidazole-Resistant <i>Bacteroides</i> Species Isolated from Hospital Patients in Kuwait

Cited by 15 publications

References 29 publications

Bacteroides Fragilis in Sepsis

Bacteroides Fragilis in Sepsis

Structural Basis of 5-Nitroimidazole Antibiotic Resistance

High-resolution structure of the antibiotic resistance protein NimA fromDeinococcus radiodurans

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