Antimicrobial drug resistance in Corynebacterium diphtheriae mitis.
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ABSTRACT:
SUBMITTER: Barraud O
PROVIDER: S-EPMC3310561 | biostudies-literature | 2011 Nov
REPOSITORIES: biostudies-literature
Publications
Antimicrobial drug resistance in Corynebacterium diphtheriae mitis.
Barraud Olivier O Badell Edgar E Denis François F Guiso Nicole N Ploy Marie-Cécile MC
Emerging infectious diseases 20111101 11
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Project description:BackgroundCorynebacterium diphtheriae, the agent of diphtheria, is a genetically diverse bacterial species. Although antimicrobial resistance has emerged against several drugs including first-line penicillin, the genomic determinants and population dynamics of resistance are largely unknown for this neglected human pathogen.MethodsHere, we analyzed the associations of antimicrobial susceptibility phenotypes, diphtheria toxin production, and genomic features in C. diphtheriae. We used 247 strains collected over several decades in multiple world regions, including the 163 clinical isolates collected prospectively from 2008 to 2017 in France mainland and overseas territories.ResultsPhylogenetic analysis revealed multiple deep-branching sublineages, grouped into a Mitis lineage strongly associated with diphtheria toxin production and a largely toxin gene-negative Gravis lineage with few toxin-producing isolates including the 1990s ex-Soviet Union outbreak strain. The distribution of susceptibility phenotypes allowed proposing ecological cutoffs for most of the 19 agents tested, thereby defining acquired antimicrobial resistance. Penicillin resistance was found in 17.2% of prospective isolates. Seventeen (10.4%) prospective isolates were multidrug-resistant (≥ 3 antimicrobial categories), including four isolates resistant to penicillin and macrolides. Homologous recombination was frequent (r/m = 5), and horizontal gene transfer contributed to the emergence of antimicrobial resistance in multiple sublineages. Genome-wide association mapping uncovered genetic factors of resistance, including an accessory penicillin-binding protein (PBP2m) located in diverse genomic contexts. Gene pbp2m is widespread in other Corynebacterium species, and its expression in C. glutamicum demonstrated its effect against several beta-lactams. A novel 73-kb C. diphtheriae multiresistance plasmid was discovered.ConclusionsThis work uncovers the dynamics of antimicrobial resistance in C. diphtheriae in the context of phylogenetic structure, biovar, and diphtheria toxin production and provides a blueprint to analyze re-emerging diphtheria.
| S-EPMC7694903 | biostudies-literature
Project description:The genome sequence of the human pathogen Corynebacterium diphtheriae bv. mitis strain ISS 3319 was determined and closed in this study. The genome is estimated to have 2,404,936 bp encoding 2,257 proteins. This strain also possesses a plasmid of 1,960 bp.
| S-EPMC5794954 | biostudies-literature
Project description:Corynebacterium diphtheriae strains , whole genome shotgun sequencing project.2018.Colombia.
| PRJNA650156 | ENA
Project description:Corynebacterium diphtheriae is the etiological agent of diphtheria, a disease caused by the presence of the diphtheria toxin. However, an increasing number of records report non-toxigenic C. diphtheriae infections. Here, a C. diphtheriae strain was recovered from a patient with a past history of bronchiectasis who developed a severe tracheo-bronchitis with multiple whitish lesions of the distal trachea and the mainstem bronchi. Whole-genome sequencing (WGS), performed in parallel with PCR targeting the toxin gene and the Elek test, provided clinically relevant results in a short turnaround time, showing that the isolate was non-toxigenic. A comparative genomic analysis of the new strain (CHUV2995) with 56 other publicly available genomes of C. diphtheriae revealed that the strains CHUV2995, CCUG 5865 and CMCNS703 share a lower average nucleotide identity (ANI) (95.24 to 95.39%) with the C. diphtheriae NCTC 11397T reference genome than all other C. diphtheriae genomes (>98.15%). Core genome phylogeny confirmed the presence of two monophyletic clades. Based on these findings, we propose here two new C. diphtheriae subspecies to replace the lineage denomination used in previous multilocus sequence typing studies: C. diphtheriae subsp. lausannense subsp. nov. (instead of lineage-2), regrouping strains CHUV2995, CCUG 5865, and CMCNS703, and C. diphtheriae subsp. diphtheriae subsp. nov, regrouping all other C. diphtheriae in the dataset (instead of lineage-1). Interestingly, members of subspecies lausannense displayed a larger genome size than subspecies diphtheriae and were enriched in COG categories related to transport and metabolism of lipids (I) and inorganic ion (P). Conversely, they lacked all genes involved in the synthesis of pili (SpaA-type, SpaD-type and SpaH-type), molybdenum cofactor and of the nitrate reductase. Finally, the CHUV2995 genome is particularly enriched in mobility genes and harbors several prophages. The genome encodes a type II-C CRISPR-Cas locus with 2 spacers that lacks csn2 or cas4, which could hamper the acquisition of new spacers and render strain CHUV2995 more susceptible to bacteriophage infections and gene acquisition through various mechanisms of horizontal gene transfer.
| S-EPMC6108181 | biostudies-literature
Project description:Novel nontoxigenic Corynebacterium diphtheriae was isolated from a domestic cat with severe otitis. Contact investigation and carrier study of human and animal contacts yielded 3 additional, identical isolates from cats, although no evidence of zoonotic transmission was identified. Molecular methods distinguished the feline isolates from known C. diphtheriae.
| S-EPMC3321947 | biostudies-literature
Project description:Corynebacterium diphtheriae bv. mitis str. NC03529 Genome sequencing and assembly
| PRJNA89613 | ENA
Project description:Background/Objectives: Despite a significant reduction in diphtheria incidence and mortality due to vaccination, antitoxin therapy and antibiotic treatments, a concerning resurgence is occurring in Europe. Resistance to penicillins and macrolides is emerging, resulting in a growing challenge for diphtheria management. This retrospective study aims to evaluate and compare antibiotic susceptibilities of both toxigenic Corynebacterium diphtheriae and C. ulcerans. Methods: Susceptibilities were assessed using broth microdilution-the gold standard-disk diffusion and the gradient method, and analyzed on the basis of the EUCAST breakpoint tables for the interpretation of MICs and zone diameters. Antimicrobial resistance genes and mutations were detected by analyzing whole-genome sequences (WGS). Results: A small number of C. diphtheriae isolates were resistant to the first-choice antimicrobial classes, penicillins and macrolides, while higher resistance rates were observed for ciprofloxacin (29%), tetracycline (38%) and trimethoprim-sulfamethoxazole (SXT, 85%). A good correlation was found with resistance genes and mutations detected by WGS. C. ulcerans isolates were susceptible to all tested antibiotics, except clindamycin, to which this species is naturally resistant, and a few ciprofloxacin resistances not confirmed by WGS. Diffusion techniques were found to be acceptable alternatives, but false susceptible results were detected for ciprofloxacin and tetracycline by disk diffusion and ciprofloxacin and SXT by gradient diffusion. Conclusions: Penicillins and macrolides remain the first-choice antibiotics for the treatment of diphtheria. However, antimicrobial susceptibility testing is needed for all toxigenic C. diphtheriae and C. ulcerans isolates, as resistance is emerging. Antimicrobial susceptibility testing should not be limited to penicillins and macrolides, but be extended to other antibiotics. When WGS is performed for epidemiological purposes, resistance genes and mutations should be looked for.
| S-EPMC11851535 | biostudies-literature
Project description:We reviewed Corynebacterium spp. infection cases reported in South Africa during 2015-2023. We analyzed 84 isolates from 83 patients with C. diphtheriae, as well as 1 C. belfantii and 3 C. ulcerans isolates. Among C. diphtheriae cases, we observed respiratory diphtheria (26/83 patients [31%]), endocarditis (14/83 [17%]), cutaneous diphtheria (22/83 [27%]), nonspecific respiratory illnesses (5/83 [6%]), and asymptomatic carriage (16/83 [19%]). The median patient age was 19 (range 0-88) years. Diphtheria-tetanus-pertussis vaccination was incomplete for 26% (5/19) or unknown for 68% (13/19) of children 0-9 years of age. C. diphtheriae was intermediately resistant to penicillin (82/84 [98%] isolates; MIC90 0.5 μg/mL) but susceptible to erythromycin (83/84 [99%] isolates; MIC90 0.25 μg/mL). Eighteen unique sequence types were identified, corroborating C. diphtheriae heterogeneity. Toxin-producing strains were detected among cutaneous and respiratory diphtheria cases, indicating all forms of disease require monitoring and prompt public health action to curb transmission.
| S-EPMC11878320 | biostudies-literature
Project description:Corynebacterium diphtheriae and Corynebacterium ulcerans are rarely isolated from clinical samples in Belgium. A case of toxigenic C. ulcerans in a woman is described, which confirms that this pathogen is still present. During investigation of the patient's cats, only a non-toxigenic toxin-bearing C. diphtheriae strain was detected.
| S-EPMC4184488 | biostudies-literature
Project description:Antimicrobial therapy is important for case management of diphtheria, but knowledge on the emergence of multidrug-resistance in Corynebacterium diphtheriae is scarce. We report on the genomic features of two multidrug-resistant toxigenic isolates sampled from wounds in France 3 years apart. Both isolates were resistant to spiramycin, clindamycin, tetracycline, kanamycin and trimethoprim-sulfamethoxazole. Genes ermX, cmx, aph(3')-Ib, aph(6)-Id, aph(3')-Ic, aadA1, dfrA15, sul1, cmlA, cmlR and tet(33) were clustered in two genomic islands, one consisting of two transposons and one integron, the other being flanked by two IS6100 insertion sequences. One isolate additionally presented mutations in gyrA and rpoB and was resistant to ciprofloxacin and rifampicin. Both isolates belonged to sublineage 453 (SL453), together with 25 isolates from 11 other countries (https://bigsdb.pasteur.fr/diphtheria/). SL453 is a cosmopolitan toxigenic sublineage of C. diphtheriae, a subset of which acquired multidrug resistance. Even though penicillin, amoxicillin and erythromycin, recommended as the first line in the treatment of diphtheria, remain active, surveillance of diphtheria should consider the risk of dissemination of multidrug-resistant strains and their genetic elements.
| S-EPMC9973851 | biostudies-literature