Project description:We report intestinal carriage of an extended-spectrum β-lactamase-producing Klebsiella pneumoniae strain with high-level resistance to colistin (MIC 24 mg/L) in a patient in France who had been hospitalized for fungal meningitis. The strain had the mcr-1 plasmid gene and an inactivated mgrB gene, which are associated with colistin resistance.
Project description:Raw milk cheeses are commonly consumed in France and are also a common source of foodborne outbreaks (FBOs). Both an FBO surveillance system and a laboratory-based surveillance system aim to detect Salmonella outbreaks. In early August 2018, five familial FBOs due to Salmonella spp. were reported to a regional health authority. Investigation identified common exposure to a raw goats' milk cheese, from which Salmonella spp. were also isolated, leading to an international product recall. Three weeks later, on 22 August, a national increase in Salmonella Newport ST118 was detected through laboratory surveillance. Concomitantly isolates from the earlier familial clusters were confirmed as S. Newport ST118. Interviews with a selection of the laboratory-identified cases revealed exposure to the same cheese, including exposure to batches not included in the previous recall, leading to an expansion of the recall. The outbreak affected 153 cases, including six cases in Scotland. S. Newport was detected in the cheese and in the milk of one of the producer's goats. The difference in the two alerts generated by this outbreak highlight the timeliness of the FBO system and the precision of the laboratory-based surveillance system. It is also a reminder of the risks associated with raw milk cheeses.
Project description:Colistin-resistance mediated by mobilisable and plasmid-borne mcr genes has emerged worldwide, threatening the efficacy of colistin, a last resort antibiotic increasingly used for treating human invasive infections by multidrug-resistant or extensively drug-resistant Enterobacteriaceae. In this study, we report the first evidence of mcr-1-mediated colistin resistance in four multidrug resistant (MDR) out of 324 Salmonella infantis from the Italian antimicrobial resistance (AMR) monitoring (2001-2017) in broilers and broiler meat. Two were also Extended Spectrum Beta-Lactamases (ESBL)-producing isolates. Characterization by whole genome sequencing (WGS), located mcr-1.1 on an incX4 plasmid. Phylogenetic analysis of these isolates with selected Italian S. Infantis previously isolated from animals, meat and human clinical cases with unknown epidemiological relationship, demonstrated that ESBL-producing, mcr-1-positive isolates belonged to the emerging pESI-like-positive-ESBL-producing clone described in Italy in 2015.
Project description:Colistin resistance in bacteria has become a significant threat to food safety and public health, and its development was mainly attributed to the plasmid-mediated mcr genes. This study aimed to determine the global prevalence and molecular characteristics of mcr-producing Salmonella enterica isolates. A total of 2279 mcr-producing Salmonella genomes were obtained from the public database, which were disseminated in 37 countries from five continents worldwide, including Asia, Europe, America, Australia, and Africa. Human samples (39.5%; 900/2279) were the predominant sources of mcr-producing Salmonella isolates, followed by foods (32.6%), animals (13.7%), and environment (4.4%). Furthermore, 80 Salmonella serotypes were identified, and Typhimurium and 1,4,[5],12:i:- were the predominant serotypes, accounting for 18.3% and 18.7%, respectively. Twenty mcr variants were identified, and the most common ones were mcr-9.1 (65.2%) and mcr-1.1 (24.4%). Carbapenems-resistance gene blaNDM-1 and tigecycline-resistance gene tet(X4) were identified in one isolate, respectively. Phylogenetic results indicated that mcr-producing Salmonella fell into nine lineages (Lineages I-IX), and Salmonella Typhimurium, 1,4,[5],12:i:- and 4,[5],12:i:- isolates from different countries were mixed in Lineages I, II and III, suggesting that international spread occurred. These findings underline further challenges for the spread of Salmonella-bearing mcr genes.
Project description:Characterization of transmission routes of Salmonella among various food-animal reservoirs and their antibiogram is crucial for appropriate intervention and medical treatment. Here, we analyzed 3728 Salmonella enterica serovar Newport (S. Newport) isolates collected from various food-animals, retail meats and humans in the United States between 1996 and 2015, based on their minimum inhibitory concentration (MIC) toward 27 antibiotics. Random Forest and Hierarchical Clustering statistic was used to group the isolates according to their MICs. Classification and Regression Tree (CART) analysis was used to identify the appropriate antibiotic and its cut-off value between human- and animal-population. Two distinct populations were revealed based on the MICs of individual strain by both methods, with the animal population having significantly higher MICs which correlates to antibiotic-resistance (AR) phenotype. Only ∼9.7% (267/2763) human isolates could be attributed to food-animal origins. Furthermore, the isolates of animal origin had less diverse antibiogram than human isolates (P < 0.001), suggesting multiple sources involved in human infections. CART identified trimethoprim-sulfamethoxazole to be the best classifier for differentiating the animal and human isolates. Additionally, two typical AR patterns, MDR-Amp and Tet-SDR dominant in bovine- or turkey-population, were identified, indicating that distinct food-animal sources could be involved in human infections. The AR analysis suggested fluoroquinolones (i.e., ciprofloxacin), but not extended-spectrum cephalosporins (i.e., ceftriaxone, cefoxitin), is the adaptive choice for empirical therapy. Antibiotic-resistant S. Newport from humans has multiple origins, with distinct food-animal-borne route contributing to a significant proportion of heterogeneous isolates.
Project description:The emergence and spread of the mobile colistin resistance gene (mcr-1) has become a major global public health concern. So far, this gene has been widely detected in food animals, pets, food, and humans. However, there is little information on the contamination of mcr-1-containing bacteria in farming soils. In August 2016, a survey of ESBL-producing Escherichia coli isolated from farming soils was conducted in Shandong Province, China. We observed colistin resistance in 12 of 53 (22.6%) ESBL-producing Enterobacteriaceae isolates from farming soil. Six mcr-1-positive E. coli strains originating from a livestock-intensive area were found. The isolates belonged to four different STs (ST2060, ST3014, ST6756, and ST1560) and harbored extensive additional resistance genes. An E. coli with blaNDM-1 was also detected in a soil sample from the same area. Comparative whole genome sequencing and S1-PFGE analysis indicated that mcr-1 was chromosomally encoded in four isolates and located on IncHI2 plasmids in two isolates. To our knowledge, we report the first isolation of mcr-1 in ESBL-producing E. coli from farming soils. This work highlights the importance of active surveillance of colistin-resistant organisms in soil. Moreover, investigations addressing the influence of animal manure application on the transmission of mcr-1-producing bacteria are also warranted.
Project description:Polymyxin acts as an ultimate line of refuge against the severe infections by multidrug-resistant Gram-negative pathogens. This conventional idea is challenged dramatically by the recent discovery of mobile colistin resistance gene (mcr-1) is prevalent in food animals and human beings worldwide. More importantly, the mcr-1 gene was found to be co-localized with other antibiotic resistance genes, raising the possibility that super-bugs with pan-drug resistance are emerging. However, little is reported on the genomes of the mcr-1-positive bacterial host reservoirs. Here we report genome sequencing of three human isolates of the mcr-1-positive Escherichia coli (E15004, E15015 and E15017) and define general features through analyses of bacterial comparative genomics. Further genomic mining together with sequence typing allowed us to elucidate that the MCR-1-carrying E. coli E15017 belongs to the sequence type ST648 and coproduces extended-spectrum ?-lactamase (ESBL). Given the fact that ST648 has been known to associate with either New Delhi metallo-?-lactamase 1 or ESBL, our results highlighted the possibility of ST648 as an epidemic clone with multidrug resistances.
Project description:BACKGROUND:Colistin resistance mediated by mcr-1-harbouring plasmids is an emerging threat in Enterobacteriaceae, like Salmonella. Based on its major contribution to the diarrhoea burden, the epidemic state and threat of mcr-1-harbouring Salmonella in community-acquired infections should be estimated. METHODS:This retrospective study analysed the mcr-1 gene incidence in Salmonella strains collected from a surveillance on diarrhoeal outpatients in Shanghai Municipality, China, 2006-2016. Molecular characteristics of the mcr-1-positive strains and their plasmids were determined by genome sequencing. The transfer abilities of these plasmids were measured with various conjugation strains, species, and serotypes. FINDINGS:Among the 12,053 Salmonella isolates, 37 mcr-1-harbouring strains, in which 35 were serovar Typhimurium, were detected first in 2012 and with increasing frequency after 2015. Most patients infected with mcr-1-harbouring strains were aged <5?years. All strains, including fluoroquinolone-resistant and/or extended-spectrum ?-lactamase-producing strains, were multi-drug resistant. S. Typhimurium had higher mcr-1 plasmid acquisition ability compared with other common serovars. Phylogeny based on the genomes combined with complete plasmid sequences revealed some clusters, suggesting the presence of mcr-1-harbouring Salmonella outbreaks in the community. Most mcr-1-positive strains were clustered together with the pork strains, strongly suggesting pork consumption as a main infection source. INTERPRETATION:The mcr-1-harbouring Salmonella prevalence in community-acquired diarrhoea displays a rapid increase trend, and the ESBL-mcr-1-harbouring Salmonella poses a threat for children. These findings highlight the necessary and significance of prohibiting colistin use in animals and continuous monitoring of mcr-1-harbouring Salmonella.
Project description:BackgroundThe Salmonella enterica serovar Newport red onion outbreak of 2020 was the largest foodborne outbreak of Salmonella in over a decade. The epidemiological investigation suggested two farms as the likely source of contamination. However, single nucleotide polymorphism (SNP) analysis of the whole genome sequencing data showed that none of the Salmonella isolates collected from the farm regions were linked to the clinical isolates-preventing the use of phylogenetics in source identification. Here, we explored an alternative method for analyzing the whole genome sequencing data driven by the hypothesis that if the outbreak strain had come from the farm regions, then the clinical isolates would disproportionately contain plasmids found in isolates from the farm regions due to horizontal transfer.ResultsSNP analysis confirmed that the clinical isolates formed a single, nearly-clonal clade with evidence for ancestry in California going back a decade. The clinical clade had a large core genome (4,399 genes) and a large and sparsely distributed accessory genome (2,577 genes, at least 64% on plasmids). At least 20 plasmid types occurred in the clinical clade, more than were found in the literature for Salmonella Newport. A small number of plasmids, 14 from 13 clinical isolates and 17 from 8 farm isolates, were found to be highly similar (> 95% identical)-indicating they might be related by horizontal transfer. Phylogenetic analysis was unable to determine the geographic origin, isolation source, or time of transfer of the plasmids, likely due to their promiscuous and transient nature. However, our resampling analysis suggested that observing a similar number and combination of highly similar plasmids in random samples of environmental Salmonella enterica within the NCBI Pathogen Detection database was unlikely, supporting a connection between the outbreak strain and the farms implicated by the epidemiological investigation.ConclusionHorizontally transferred plasmids provided evidence for a connection between clinical isolates and the farms implicated as the source of the outbreak. Our case study suggests that such analyses might add a new dimension to source tracking investigations, but highlights the need for detailed and accurate metadata, more extensive environmental sampling, and a better understanding of plasmid molecular evolution.
Project description:BACKGROUND:Fluoroquinolone resistance and ESBL-production are concurrently found in a limited number of Salmonella serotypes. The present study was aimed to characterize fluoroquinolone-resistant and ESBL-producing Salmonella enteric serotype Derby (S. Derby) isolates in terms of antimicrobial susceptibility, relevant genetic mechanisms, and PFGE. RESULTS:From 2013 to 2017 in Ningbo China, 52 S. Derby isolates were identified out of 826 non-typhoidal Salmonella isolates from patient feces, food, and environmental water samples. Three S. derby isolates were identified to be fluoroquinolone-resistant and ESBL-producing with cefotaxime MIC of 64 μg/mL and ciprofloxacin MIC of 4 μg/mL. The three isolates contained the same genetic structure of quinolone resistance, including a silent gyrA mutation S (TCC) 83S (TCT) and three PMQR genes qnrB, qnrS and aac(6')-Ib-cr. As withβ-lactams resistance mechanisms, two isolates contained blaTEM, blaOXA, and blaCTX-M genes and one isolate contained blaOXA and blaCTX-M genes. Additionally, two isolates displayed more identical PFGE pattern than the third isolate, whereas three isolates showed the same plasmid profile of I1, W and P by PCR-based replicon typing. The conjugation experiment showed no dissemination of β-lactam resistance by direct contact among isolates; the transformation experiment failed to transfer plasmid conferring ampicillin resistance to E. coli DH5a. CONCLUSION:The present study demonstrates the emerging fluoroquinolone-resistant and ESBL-producing S. Derby in both humans and the environment. Seeing that S. Derby has become one of the most common Salmonella serotypes, this situation gives rise to a new major risk of food-borne diseases.