nim gene-independent metronidazole-resistant Bacteroides fragilis in surgical site infections

Akhi, Mohammad Taghi; Ghotaslou, Reza; Alizadeh, Naser; Yekani, Mina; Beheshtirouy, Samad; Asgharzadeh, Mohammad; Pirzadeh, Tahereh; Memar, Mohammad Yousef

doi:10.3205/dgkh000298

“…The European data from the early 1990s showed no resistance, but in the succeeding years, there was an increase to 0.5% [31][32][33]. On the contrary, a significantly higher resistance of up to 15% has been seen in many western countries [34][35][36] and up to 30% from a few Asian regions [22,[35][36][37][38]. In our study, a 41.1% resistance was seen in Bacteroides spp., whereas resistance varying from 7% to 31% has been reported in other Indian studies [26,39].…”

Section: Discussioncontrasting

confidence: 59%

Anaerobic Gram-Negative Bacteria: Role as a Reservoir of Antibiotic Resistance

Sood

¹

,

Ray

²

,

Angrup

³

2023

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Background: Anaerobic Gram-negative bacteria (AGNB) play a significant role as both pathogens and essential members of the human microbiota. Despite their clinical importance, there remains limited understanding regarding their antimicrobial resistance (AMR) patterns. This knowledge gap poses challenges in effectively managing AGNB-associated infections, as empirical treatment approaches may not adequately address the evolving resistance landscape. To bridge this research gap, we conducted a comprehensive study aimed at exploring the role of human AGNB as a reservoir of AMR. This can provide valuable insights for the prevention and management of anaerobic infections. Methods: We studied the prevalence of AMR and AMR determinants conferring resistance to metronidazole (nimE), imipenem (cfiA), piperacillin–tazobactam (cepA), cefoxitin (cfxA), clindamycin (ermF), chloramphenicol (cat) and mobile genetic elements (MGEs) such as cfiAIS and IS1186 associated with the cfiA and nim gene expression. These parameters were studied in Bacteroides spp., Fusobacterium spp., Prevotella spp., Veillonella spp., Sutterella spp., and other clinical AGNB. Results: Resistance to metronidazole, clindamycin, imipenem, piperacillin–tazobactam, cefoxitin and chloramphenicol was 29%, 33.5%, 0.5%, 27.5%, 26.5% and 0%, respectively. The presence of resistance genes, viz., nim, ermF, cfiA, cepA, cfxA, was detected in 24%, 33.5%, 10%, 9.5%, 21.5% isolates, respectively. None of the tested isolates showed the presence of a cat gene and MGEs, viz., cfiAIS and IS1186. The highest resistance to all antimicrobial agents was exhibited by Bacteroides spp. The association between resistant phenotypes and genotypes was complete in clindamycin, as all clindamycin-resistant isolates showed the presence of ermF gene, and none of the susceptible strains harbored this gene; similarly, all isolates were chloramphenicol-susceptible and also lacked the cat gene, whereas the association was low among imipenem and piperacillin–tazobactam. Metronidazole and imipenem resistance was seen to be dependent on insertion sequences for the expression of AMR genes. A constrained co-existence of cepA and cfiA gene in B. fragilis species was seen. Based on the absence and presence of the cfiA gene, we divided B. fragilis into two categories, Division I (72.6%) and Division II (27.3%), respectively. Conclusion: AGNB acts as a reservoir of specific AMR genes, which may pose a threat to other anaerobes due to functional compatibility and acquisition of these genes. Thus, AST-complying standard guidelines must be performed periodically to monitor the local and institutional susceptibility trends, and rational therapeutic strategies must be adopted to direct empirical management.

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“…fragilis clinical isolates in recent studies [87–90]. While the nitroimidazole reductase enzyme that is encoded by nim genes is responsible for contributing to reduced metronidazole susceptibility in encoding strains, by inhibiting the formation of toxic nitroso residues, metronidazole resistance can occur in the absence of these AMR genes and indicates that other mechanisms can confer metronidazole resistance [88, 91]. Such unrelated nim gene mechanisms include overexpression of multidrug efflux pumps and the DNA repair protein, RecA, as well as ferrous iron transporter deficiency [92–94].…”

Section: Resultsmentioning

confidence: 99%

Genomic analyses of Bacteroides fragilis: subdivisions I and II represent distinct species

English,

Newberry,

Hoyles

et al. 2023

Journal of Medical Microbiology

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Introduction. Bacteroides fragilis is a Gram-negative anaerobe that is a member of the human gastrointestinal microbiota and is frequently found as an extra-intestinal opportunistic pathogen. B. fragilis comprises two distinct groups – divisions I and II – characterized by the presence/absence of genes [cepA and ccrA (cfiA), respectively] that confer resistance to β-lactam antibiotics by either serine or metallo-β-lactamase production. No large-scale analyses of publicly available B. fragilis sequence data have been undertaken, and the resistome of the species remains poorly defined. Hypothesis/Gap Statement. Reclassification of divisions I and II B. fragilis as two distinct species has been proposed but additional evidence is required. Aims. To investigate the genomic diversity of GenBank B. fragilis genomes and establish the prevalence of division I and II strains among publicly available B. fragilis genomes, and to generate further evidence to demonstrate that B. fragilis division I and II strains represent distinct genomospecies. Methodology. High-quality (n=377) genomes listed as B. fragilis in GenBank were included in pangenome and functional analyses. Genome data were also subject to resistome profiling using The Comprehensive Antibiotic Resistance Database. Results. Average nucleotide identity and phylogenetic analyses showed B. fragilis divisions I and II represent distinct species: B. fragilis sensu stricto (n=275 genomes) and B. fragilis A (n=102 genomes; Genome Taxonomy Database designation), respectively. Exploration of the pangenome of B. fragilis sensu stricto and B. fragilis A revealed separation of the two species at the core and accessory gene levels. Conclusion. The findings indicate that B. fragilis A, previously referred to as division II B. fragilis , is an individual species and distinct from B. fragilis sensu stricto. The B. fragilis pangenome analysis supported previous genomic, phylogenetic and resistome screening analyses collectively reinforcing that divisions I and II are two separate species. In addition, it was confirmed that differences in the accessory genes of B. fragilis divisions I and II are primarily associated with carbohydrate metabolism and suggest that differences other than antimicrobial resistance could also be used to distinguish between these two species.

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Collateral sensitivity: An evolutionary trade‐off between antibiotic resistance mechanisms, attractive for dealing with drug‐resistance crisis

Yekani

¹

,

Azargun

²

,

Sharifi

³

et al. 2023

Health Science Reports

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Background: The discovery and development of antimicrobial drugs were one of the most significant advances in medicine, but the evolution of microbial resistance limited the efficiency of these drugs.Aim: This paper reviews the collateral sensitivity in bacteria and its potential and limitation as a new target for treating infections.Results and Discussion: Knowledge mechanisms of resistance to antimicrobial agents are useful to trace a practical approach to treat and control of resistant pathogens. The effect of a resistance mechanism to certain antibiotics on the susceptibility or resistance to other drugs is a key point that may be helpful for applying a strategy to control resistance challenges. In an evolutionary trade-off known as collateral sensitivity, the resistance mechanism to a certain drug may be mediated by the hypersensitivity to other drugs. Collateral sensitivity has been described for different drugs in various bacteria, but the molecular mechanisms affecting susceptibility are not well demonstrated. Collateral sensitivity could be studied to detect its potential in the battle against resistance crisis as well as in the treatment of pathogens adapting to antibiotics. Collateral sensitivity-based antimicrobial therapy may have the potential to limit the emergence of antibiotic resistance.

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nim gene-independent metronidazole-resistant Bacteroides fragilis in surgical site infections

Cited by 10 publications

References 23 publications

Anaerobic Gram-Negative Bacteria: Role as a Reservoir of Antibiotic Resistance

Anaerobic Gram-Negative Bacteria: Role as a Reservoir of Antibiotic Resistance

Genomic analyses of Bacteroides fragilis: subdivisions I and II represent distinct species

Collateral sensitivity: An evolutionary trade‐off between antibiotic resistance mechanisms, attractive for dealing with drug‐resistance crisis

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