Pervasive transmission of a carbapenem resistance plasmid in the gut microbiota of hospitalized patients.
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ABSTRACT:
SUBMITTER: Leon-Sampedro R
PROVIDER: S-EPMC7610705 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The massive and irrational use of antibiotics in livestock productions has fostered the occurrence and spread of resistance to "old class antimicrobials." To cope with that phenomenon, some regulations have been already enforced in the member states of the European Union. However, a role of livestock animals in the relatively recent alerts on the rapid worldwide increase of resistance to last-choice antimicrobials as carbapenems is very unlikely. Conversely, these antimicrobials are increasingly administered in veterinary hospitals whose role in spreading bacteria or mobile genetic elements has not adequately been addressed so far. A cross-sectional study was carried out on 105 hospitalized and 100 non-hospitalized pets with the aim of measuring the prevalence of carbapenem-resistant Gram-negative bacteria (GNB) colonizing dogs and cats, either hospitalized or not hospitalized and estimating the relative odds. Stool samples were inoculated on MacConkey agar plates containing 1 mg/L imipenem which were then incubated aerobically at 37°C ± 1 for 48 h. Isolated bacteria were identified first by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and were confirmed by 16S rRNA sequencing. The genetic basis of resistance was investigated using PCR methods, gene or whole genome sequencing (WGS). The prevalence of pets harboring carbapenem-resistant bacteria was 11.4 and 1.0% in hospitalized and not-hospitalized animals, respectively, with an odds ratio of 12.8 (p < 0.01). One pet carried two diverse isolates. Overall, 14 gram-negative non-fermenting bacteria, specifically, one Acinetobacter radioresistens, five Acinetobacter baumannii, six Pseudomonas aeruginosa and two Stenotrophomonas maltophilia were isolated. The Acinetobacter species carried acquired carbapenemases genes encoded by bla NDM-1 and bla OXA-23. In contrast, Pseudomonas phenotypic resistance was associated with the presence of mutations in the oprD gene. Notably, inherent carbapenem-resistant isolates of S. maltophilia were also resistant to the first-line recommended chemotherapeutic trimethoprim/sulfamethoxazole. This study estimates the risk of colonization by carbapenem-resistant non-fermenting GNB in pets hospitalized in veterinary tertiary care centers and highlights their potential role in spreading resistance genes among the animal and human community. Public health authorities should consider extending surveillance systems and putting the release of critical antibiotics under more strict control in order to manage the infection/colonization of pets in veterinary settings.
| S-EPMC6291488 | biostudies-literature
Project description:Reduced biodiversity and increased representation of opportunistic pathogens are typical features of gut microbiota composition in aging. Few studies have investigated their correlation with polypharmacy, multimorbidity and frailty. To assess it, we analyzed the fecal microbiota from 76 inpatients, aged 83?±?8. Microbiome biodiversity (Chao1 index) and relative abundance of individual bacterial taxa were determined by next-generation 16S rRNA microbial profiling. Their correlation with number of drugs, and indexes of multimorbidity and frailty were verified using multivariate linear regression models. The impact of gut microbiota biodiversity on mortality, rehospitalizations and incident sepsis was also assessed after a 2-year follow-up, using Cox regression analysis. We found a significant negative correlation between the number of drugs and Chao1 Index at multivariate analysis. The number of drugs was associated with the average relative abundance of 15 taxa. The drug classes exhibiting the strongest association with single taxa abundance were proton pump inhibitors, antidepressants and antipsychotics. Conversely, frailty and multimorbidity were not significantly associated with gut microbiota biodiversity. Very low Chao1 index was also a significant predictor of mortality, but not of rehospitalizations and sepsis, at follow-up. In aging, polypharmacy may thus represent a determinant of gut microbiota composition, with detrimental clinical consequences.
| S-EPMC5593887 | biostudies-literature
Project description:UnlabelledColistin is an ultimate line of refuge against multidrug-resistant Gram-negative pathogens. Very recently, the emergence of plasmid-mediatedmcr-1colistin resistance has become a great challenge to global public health, raising the possibility that dissemination of themcr-1gene is underestimated and diversified. Here, we report three cases of plasmid-carried MCR-1 colistin resistance in isolates from gut microbiota of diarrhea patients. Structural and functional analyses determined that the colistin resistance is conferred purely by the singlemcr-1gene. Genetic and sequence mapping revealed thatmcr-1-harbouring plasmid reservoirs are present in diversity. Together, the data represent the first evidence of diversity inmcr-1-harbouring plasmid reservoirs of human gut microbiota.ImportanceThe plasmid-mediated mobile colistin resistance gene (mcr-1) challenged greatly the conventional idea mentioned above that colistin is an ultimate line of refuge against lethal infections by multidrug-resistant Gram-negative pathogens. It is a possibility that diversified dissemination of themcr-1gene might be greatly underestimated. We report three cases of plasmid-carried MCR-1 colistin resistance in isolates from gut microbiota of diarrhea patients and functionally define the colistin resistance conferred purely by the singlemcr-1gene. Genetic and sequence mapping revealed unexpected diversity among themcr-1-harbouring plasmid reservoirs of human gut microbiota.
| S-EPMC4817250 | biostudies-literature
Project description:Klebsiella pneumoniae poses a critical challenge to clinical and public health. Along with conjugative plasmids, nonconjugative resistance or virulence plasmids associated with carbapenem-resistant K. pneumoniae (CRKP), hypervirulent K. pneumoniae (hvKP), and even carbapenem-resistant and hypervirulent K. pneumoniae (CR-hvKP) strains have been spreading globally. In this study, a clinical CRKP strain KP2648 was isolated, and the transferability of its plasmids was assessed using conjugation experiments. The transconjugants were characterized by polymerase chain reaction (PCR) detection, XbaI and S1-pulsed-field gel electrophoresis (PFGE), and/or whole-genome sequencing. Genetically modified IncN3 plasmids were employed to elucidate the self-transferability and the mobilization mechanisms. KP2648 has three natural plasmids: a nonconjugative IncFIB/IncHI3B virulence plasmid, a nonconjugative IncFII/IncR carbapenem-resistant plasmid, and a self-transferable IncN3 plasmid with a high conjugation frequency (7.54 ± 1.06) × 10-1. The IncN3 plasmid could mobilize the coexisting nonconjugative virulence/resistance plasmids either directly or by employing intermediate E. coli with two forms: a hybrid plasmid fused with IncN3 or a cotransfer with the helper plasmid, IncN3. Various mobile genetic elements, including ISKpn74, ISKpn14, IS26, ISShes11, ISAba11, and Tn3, are involved in the genetic transposition of diverse hybrid plasmids and the cotransfer process during the intra/interspecies transmission. IMPORTANCE Nowadays, the underlying mobilization mechanism and evolutionary processes of nonconjugative virulence or resistance plasmids in Klebsiella pneumoniae remain poorly understood. Our study revealed the high conjugation ability of IncN3 plasmid isolated from carbapenem-resistant K. pneumoniae and confirmed its capability to mobilize the nonconjugative virulence or resistance plasmids. The self-transferable IncN3 plasmid could facilitate the transmission of pathogenicity and genetic evolution of carbapenem-resistant and hypervirulent K. pneumoniae, including hv-CRKP (virulence plasmid obtained by carbapenem-resistant K. pneumoniae) and CR-hvKP (resistance plasmid obtained by hypervirulent K. pneumoniae), warranting further monitoring.
| S-EPMC9430514 | biostudies-literature
Project description:To understand how antibiotic use affects the risk of a resistant infection, we present a computational model of the population dynamics of gut microbiota including antibiotic resistance-conferring plasmids. We then describe how this model is parameterized based on published microbiota data. Finally, we investigate how treatment history affects the prevalence of resistance among opportunistic enterobacterial pathogens. We simulate treatment histories and identify which properties of prior antibiotic exposure are most influential in determining the prevalence of resistance. We find that resistance prevalence can be predicted by 3 properties, namely the total days of drug exposure, the duration of the drug-free period after last treatment, and the center of mass of the treatment pattern. Overall this work provides a framework for capturing the role of the microbiome in the selection of antibiotic resistance and highlights the role of treatment history for the prevalence of resistance.
| S-EPMC6859334 | biostudies-literature
Project description:Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. Therefore, we evaluated the alteration of the intestinal microbiota associated with CRE colonization in critically ill patients. Methods Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. The analysis of bacterial metabolic abundance to identify an association between CRE acquisition and metabolic pathway was performed. Results CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. The alpha-diversity indices were significantly decreased in CRE carriers, and beta-diversity analysis demonstrated that the two groups were clustered significantly apart. Among short-chain fatty acids, the levels of isobutyric acid and valeric acid were significantly decreased in CRE carriers. Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. Conclusion Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. Further studies are needed to determine whether amino acids supplementation improves microbiota dysbiosis in patients with CRE.
| S-EPMC10110853 | biostudies-literature
Project description:Non-caloric artificial sweeteners have been widely permitted as table sugar substitutes with high intensities of sweetness. They can pass through the intestinal tract without significant metabolization and frequently encounter the gut microbiome, which is composed of diverse bacterial species and is a pool of antibiotic resistance genes (ARGs). However, little is known about whether these sweeteners could accelerate the spread of ARGs in the gut microbiome. Here, we established an in vitro conjugation model by using Escherichia coli that carries chromosome-inserted Tn7 lacIq-pLpp-mCherry and plasmid-encoded gfpmut3b gene as the donor and murine fecal bacteria as the recipient. We found that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) can increase reactive oxygen species (ROS) production and promote plasmid-mediated conjugative transfer to the gut microbiome. Cell sorting and 16S rRNA gene amplicon sequencing analysis of fecal samples reveal that the tested sweeteners can promote the broad-host-range plasmid permissiveness to both Gram-negative and Gram-positive gut bacteria. The increased plasmid permissiveness was also validated with a human pathogen Klebsiella pneumoniae. Collectively, our study demonstrates that non-caloric artificial sweeteners can induce oxidative stress and boost the plasmid-mediated conjugative transfer of ARGs among the gut microbiota and a human pathogen. Considering the soaring consumption of these sweeteners and the abundance of mobile ARGs in the human gut, our results highlight the necessity of performing a thorough risk assessment of antibiotic resistance associated with the usage of artificial sweeteners as food additives.
| S-EPMC9762752 | biostudies-literature
Project description:Although AmpC ?-lactamases can barely degrade carbapenems, if at all, they can sequester them and prevent them from reaching their targets. Thus, carbapenem resistance in Escherichia coli and other Enterobacteriaceae can result from AmpC production and simultaneous reduction of antibiotic influx into the periplasm by mutations in the porin genes. Here we investigated the route and genetic mechanisms of acquisition of carbapenem resistance in a clinical E. coli isolate carrying blaCMY-2 on a plasmid by selecting for mutants that are resistant to increasing concentrations of meropenem. In the first step, the expression of OmpC, the only porin produced in the strain under laboratory conditions, was lost, leading to reduced susceptibility to meropenem. In the second step, the expression of the CMY-2 ?-lactamase was upregulated, leading to resistance to meropenem. The loss of OmpC was due to the insertion of an IS1 element into the ompC gene or to frameshift mutations and premature stop codons in this gene. The blaCMY-2 gene was found to be located on an IncI? plasmid, and overproduction of the CMY-2 enzyme resulted from an increased plasmid copy number due to a nucleotide substitution in the inc gene. The clinical relevance of these genetic mechanisms became evident from the analysis of previously isolated carbapenem-resistant clinical isolates, which appeared to carry similar mutations.
| S-EPMC5192137 | biostudies-literature
Project description:Acinetobacter baumannii is an opportunistic pathogen that poses an increasing threat in the health-care community. Colistin is one of the promising options for treatment of multidrug-resistant A. baumannii. The current study investigated the emergence of colistin resistance among carbapenem-resistant strains of A. baumannii in Egypt. It involved identification of clinically recovered A. baumannii isolates using the VITEK-2 system, and screening of their antimicrobial susceptibilities using broth microdilution techniques. Characterizations of carbapenemase and 16S rRNA methyltransferase genes were performed using PCR. Colistin-resistance determinants were characterized by sequencing. Carbapenem-resistant A. baumannii isolates (n = 40) showed resistance to amoxicillin-clavulanic acid, cefotaxime, gentamicin and amikacin. Most isolates revealed resistance to ciprofloxacin (95%; n = 38) and co-trimoxazole (92.5%; n = 37). Resistance to tobramycin and doxycycline was 80% (n = 32) and 62.5% (n = 25), respectively. Only two A. baumannii isolates demonstrated colistin resistance. Carbapenemase activity was tested by modified Hodge test and 78% of isolates were positive. All isolates carried blaOXA-51-like genes whereas bla-OXA-23 was detected in 80% (n = 32) of isolates. Among 16S rRNA methylase genes, armA was detected in 22.5% (n = 9) of the isolates. Analyses of lpxA, lpxC, lpxD and pmrCAB genetic sequences suggest that colistin resistance could be attributed to mutations in pmrCAB genes. Alarmingly, colistin resistance was associated with high levels of resistance to other antimicrobials. The current findings represent a serious health-care problem capable of restraining future therapeutic options.
| S-EPMC6138847 | biostudies-literature
Project description:We used a DNA microarray chip covering 369 resistance types to investigate the relation of antibiotic resistance gene diversity with humansM-bM-^@M-^Y age. Metagenomic DNA from fecal samples of 123 healthy volunteers of four different age groups, i.e. pre-school Children (CH), School Children (SC), High School Students (HSS) and Adults (AD) were used for hybridization. The results showed that 80 different gene types were recovered from the 123 individuals gut microbiota, among which 25 were present in CH, 37 in SC, 58 in HSS and 72 in AD. Further analysis indicated that antibiotic resistance genes in groups of CH, SC and AD can be independently clustered, and those ones in group HSS are more divergent. The detailed analysis of antibiotic resistance genes in human gut is further described in the paper DNA microarray analysis reveals the antibiotic resistance gene diversity in human gut microbiota is age-related submitted to Sentific Reports The antibiotic resistance gene microarray is custom-designed (Roche NimbleGen), based on a single chip containing 3 internal replicated probe sets of 12 probes per resistance gene, covering the whole 315K 12-plex platform spots.
2014-01-16 | E-GEOD-54070 | biostudies-arrayexpress