A cfr- like gene cfr (C) conferring linezolid resistance is common in Clostridium difficile

Candela, Thomas; Marvaud, Jean-Christophe; Nguyen, Tiep Khac; Lambert, Thierry

doi:10.1016/j.ijantimicag.2017.03.013

Cited by 43 publications

(25 citation statements)

References 19 publications

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“…Resistance to MLS antibiotics in C. difficile is usually due to ribosomal methylation mediated by the rRNA adenine N-6-methyltransferase encoded by ermB , and also, but less frequently, by the chloramphenicol-florfenicol resistance gene, cfr , which encodes a 23S rRNA methyltransferase that confers resistance to linezolid (Candela et al, 2017). Both these genes are carried by mobile genetic elements such as conjugative transposons (Spigaglia, 2016).…”

Section: Discussionmentioning

confidence: 99%

Genomic Study of a Clostridium difficile Multidrug Resistant Outbreak-Related Clone Reveals Novel Determinants of Resistance

et al. 2018

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Background: Clostridium difficile infection (CDI) is prevalent in healthcare settings. The emergence of hypervirulent and antibiotic resistant strains has led to an increase in CDI incidence and frequent outbreaks. While the main virulence factors are the TcdA and TcdB toxins, antibiotic resistance is thought to play a key role in the infection by and dissemination of C. difficile.Methods: A CDI outbreak involving 12 patients was detected in a tertiary care hospital, in Lisbon, which extended from January to July, with a peak in February, in 2016. The C. difficile isolates, obtained from anaerobic culture of stool samples, were subjected to antimicrobial susceptibility testing with Etest®strips against 11 antibiotics, determination of toxin genes profile, PCR-ribotyping, multilocus variable-number tandem-repeat analysis (MLVA) and whole genome sequencing (WGS).Results: Of the 12 CDI cases detected, 11 isolates from 11 patients were characterized. All isolates were tcdA-/tcdB+ and belonged to ribotype 017, and showed high level resistance to clindamycin, erythromycin, gentamicin, imipenem, moxifloxacin, rifampicin and tetracycline. The isolates belonged to four genetically related MLVA types, with six isolates forming a clonal cluster. Three outbreak isolates, each from a different MLVA type, were selected for WGS. Bioinformatics analysis showed the presence of several antibiotic resistance determinants, including the Thr82Ile substitution in gyrA, conferring moxifloxacin resistance, the substitutions His502Asn and Arg505Lys in rpoB for rifampicin resistance, the tetM gene, associated with tetracycline resistance, and two genes encoding putative aminoglycoside-modifying enzymes, aadE and aac(6′)-aph(2″). Furthermore, a not previously described 61.3 kb putative mobile element was identified, presenting a mosaic structure and containing the genes ermG, mefA/msrD and vat, associated with macrolide, lincosamide and streptogramins resistance. A substitution found in a class B penicillin-binding protein, Cys721Ser, is thought to contribute to imipenem resistance.Conclusion: We describe an epidemic, tcdA-/tcdB+, multidrug resistant clone of C. difficile from ribotype 017 associated with a hospital outbreak, providing further evidence that the lack of TcdA does not impair the infectious potential of these strains. We identified several determinants of antimicrobial resistance, including new ones located in mobile elements, highlighting the importance of horizontal gene transfer in the pathogenicity and epidemiological success of C. difficile.

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Section: Discussionmentioning

confidence: 99%

Genomic Study of a Clostridium difficile Multidrug Resistant Outbreak-Related Clone Reveals Novel Determinants of Resistance

et al. 2018

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“…This plasmid-mediated gene determines cross-resistance to phenicols, lincosamides, pleuromutilins, streptogramin A and oxazolidinones, including linezolid, listed as a critically important antimicrobial [41]. The gene was reported in multidrug-resistant Campylobacter and Clostridium difficile isolates [42,43]. In this light, the evidence for pathogens we found in poultry indicates a serious threat to public health.…”

Section: Plos Onementioning

confidence: 93%

A metagenomic glimpse into the gut of wild and domestic animals: Quantification of antimicrobial resistance and more

et al. 2020

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Antimicrobial resistance (AMR) in bacteria is a complex subject, why one need to look at this phenomenon from a wider and holistic perspective. The extensive use of the same antimicrobial classes in human and veterinary medicine as well as horticulture is one of the main drivers for the AMR selection. Here, we applied shotgun metagenomics to investigate the AMR epidemiology in several animal species including farm animals, which are often exposed to antimicrobial treatment opposed to an unique set of wild animals that seems not to be subjected to antimicrobial pressure. The comparison of the domestic and wild animals allowed to investigate the possible anthropogenic impact on AMR spread. Inclusion of animals with different feeding behaviors (carnivores, omnivores) enabled to further assess which AMR genes that thrives within the food chain. We tested fecal samples not only of intensively produced chickens, turkeys, and pigs, but also of wild animals such as wild boars, red foxes, and rodents. A multi-directional approach mapping obtained sequences to several databases provided insight into the occurrence of the different AMR genes. The method applied enabled also analysis of other factors that may influence AMR of intestinal microbiome such as diet. Our findings confirmed higher levels of AMR in farm animals than in wildlife. The results also revealed the potential of wildlife in the AMR dissemination. Particularly in red foxes, we found evidence of several AMR genes conferring resistance to critically important antimicrobials like quinolones and cephalosporins. In contrast, the lowest abundance of AMR was observed in rodents originating from natural environment with presumed limited exposure to antimicrobials. Shotgun metagenomics enabled us to demonstrate that discrepancies between AMR profiles found in the intestinal microbiome of various animals probably resulted from the different antimicrobial exposure, habitats, and behavior of the tested animal species.

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“…Since cfr was first identified in bovine Staphylococcus sciuri , it has also been reported in various Staphylococcus species from humans, pets, and farm animals 4,9–11 . Recently, a cfr homolog, cfr (B), has been discovered in Clostridium difficile and Enterococcus faecium strains in Europe 12,13 , while cfr (C) was identified in Campylobacter coli and Clostridium difficile 14–16 .…”

Section: Introductionmentioning

confidence: 99%

Analysis of combined resistance to oxazolidinones and phenicols among bacteria from dogs fed with raw meat/vegetables and the respective food items

Fan

Wang

et al. 2019

Sci Rep

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The gene optrA is the first gene that confers resistance to the oxazolidinone tedizolid, a last resort antimicrobial agent in human medicine. In this study we investigated the presence of optrA and the multi-resistance genes poxtA and cfr in enterococci and staphylococci from (i) pet animals known to be fed raw meat and vegetables and (ii) the respective food items. We examined 341 bacterial isolates from cats and dogs, 195 bacterial isolates from supermarket food items and only one E. faecium collected from industrial food in Beijing during 2016. Thirty-five (6.5%) of the 537 isolates, including 31/376 (8.2%) enterococci and 4/161 (2.5%) staphylococci, were positive for optrA, while all isolates were negative for poxtA and cfr. S1-nuclease pulsed-field gel electrophoresis (PFGE) and Southern blotting confirmed that optrA was located in the chromosomal DNA of 19 isolates and on a plasmid in the remaining 16 isolates. Whole genome sequencing revealed several different genetic environments of optrA in plasmid- or chromosome-borne optrA genes. PFGE, multilocus sequence typing (MLST) and/or SNP analysis demonstrated that the optrA-carrying Staphylococcus and Enterococcus isolates were genetically heterogeneous. However, in single cases, groups of related isolates were identified which might suggest a transfer of closely related optrA-positive E. faecalis isolates between food items and dogs.

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A cfr- like gene cfr (C) conferring linezolid resistance is common in Clostridium difficile

Cited by 43 publications

References 19 publications

Genomic Study of a Clostridium difficile Multidrug Resistant Outbreak-Related Clone Reveals Novel Determinants of Resistance

Genomic Study of a Clostridium difficile Multidrug Resistant Outbreak-Related Clone Reveals Novel Determinants of Resistance

A metagenomic glimpse into the gut of wild and domestic animals: Quantification of antimicrobial resistance and more

Analysis of combined resistance to oxazolidinones and phenicols among bacteria from dogs fed with raw meat/vegetables and the respective food items

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