Antibiotic exposure elicits the emergence of colistin- and carbapenem-resistant Escherichia coli coharboring MCR-1 and NDM-5 in a patient.
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ABSTRACT:
SUBMITTER: Mao J
PROVIDER: S-EPMC6067848 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
Antibiotic exposure elicits the emergence of colistin- and carbapenem-resistant Escherichia coli coharboring MCR-1 and NDM-5 in a patient.
Mao Jinpeng J Liu Wugao W Wang Wei W Sun Jian J Lei Sheng S Feng Youjun Y
Virulence 20180101 1
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Project description:The emergence of carbapenem-resistant and colistin-resistant Enterobacteriaceae represents a great risk for public health. In this study, the phenotypical and genetic characteristics of eight carbapenem-resistant and colistin-resistant isolates from pig farms in China were determined by the broth microdilution method and whole genome sequencing. Antimicrobial susceptibility testing showed that the eight carbapenem-resistant and colistin-resistant strains were resistant to three aminoglycosides, twelve β-lactams, one of the phenicols, one of the tetracyclines, and one of the fluoroquinolones tested, simultaneously. The prediction of acquired resistant genes using the whole genome sequences revealed the co-existence of blaNDM-1 and mcr-1 as well as the other genes that were responsible for the multidrug-resistant phenotypes. Bioinformatics analysis also showed that the carbapenem-resistant gene blaNDM-1 was located on a putative IncFII-type plasmid, which also carried the other acquired resistant genes identified, including fosA3, blaTEM-1B and rmtB, while the colistin-resistant gene mcr-1 was carried by a putative IncX4-type plasmid. Finally, we found that these resistant genes/plasmids were conjugative, and they could be co-conjugated, conferring resistance to multiple types of antibiotics, including the carbapenems and colistin, to the recipient Escherichiacoli strains.
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Project description:We report the presence of mcr-1 in Escherichia coli and carbapenem-resistant Cronobacter sakazakii from the same diseased chicken. The mcr-1 gene linked with ISApl1 was located on two different IncI2 plasmids, including one multidrug plasmid in E. coli, whereas fosA3-blaNDM-9 was on an IncB/O plasmid in C. sakazakii The development of the fosA3-blaNDM-9 resistance region was mediated by IS26 The colocation of mcr-1 or blaNDM-9 with other resistance genes will accelerate the dissemination of the two genes.
| S-EPMC5278688 | biostudies-literature
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| S-EPMC5192131 | biostudies-literature
Project description:Infections due to carbapenem-resistant NDM-producing Escherichia coli represent a major therapeutic challenge, especially in situations of pre-existing colistin resistance. The aim of this study was to investigate combinatorial pharmacodynamics of colistin and tigecycline against E. coli harboring bla NDM- 5 and mcr-1, with possible mechanisms explored as well. Colistin disrupted the bacterial outer-membrane and facilitated tigecycline uptake largely independent of mcr-1 expression, which allowed a potentiation of the tigecycline-colistin combination. A concentration-dependent decrease in colistin MIC and EC50 was observed with increasing tigecycline levels. Clinically relevant concentrations of colistin and tigecycline combination significantly decreased bacterial density of colistin-resistant E. coli by 3.9 to 6.1-log10 cfu/mL over 48 h at both inoculums of 106 and 108 cfu/mL, and were more active than each drug alone (P < 0.01). Importantly, colistin and tigecycline combination therapy was efficacious in the murine thigh infection model at clinically relevant doses, resulting in >2.0-log10cfu/thigh reduction in bacterial density compared to each monotherapy. These data suggest that the use of colistin and tigecycline combination can provide a therapeutic alternative for infection caused by multidrug-resistant E. coli that harbored both bla NDM- 5 and mcr-1.
| S-EPMC6960404 | biostudies-literature
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| S-EPMC4862507 | biostudies-literature
Project description:The rapid increase in carbapenem resistance among gram-negative bacteria has renewed focus on the importance of polymyxin antibiotics (colistin or polymyxin E). However, the recent emergence of plasmid-mediated colistin resistance determinants (mcr-1, -2, -3, -4, -5, -6, and -7), especially mcr-1, in carbapenem-resistant Enterobacteriaceae is a serious threat to global health. Here, we characterized a novel mobile colistin resistance gene, mcr-8, located on a transferrable 95,983-bp IncFII-type plasmid in Klebsiella pneumoniae. The deduced amino-acid sequence of MCR-8 showed 31.08%, 30.26%, 39.96%, 37.85%, 33.51%, 30.43%, and 37.46% identity to MCR-1, MCR-2, MCR-3, MCR-4, MCR-5, MCR-6, and MCR-7, respectively. Functional cloning indicated that the acquisition of the single mcr-8 gene significantly increased resistance to colistin in both Escherichia coli and K. pneumoniae. Notably, the coexistence of mcr-8 and the carbapenemase-encoding gene blaNDM was confirmed in K. pneumoniae isolates of livestock origin. Moreover, BLASTn analysis of mcr-8 revealed that this gene was present in a colistin- and carbapenem-resistant K. pneumoniae strain isolated from the sputum of a patient with pneumonia syndrome in the respiratory intensive care unit of a Chinese hospital in 2016. These findings indicated that mcr-8 has existed for some time and has disseminated among K. pneumoniae of both animal and human origin, further increasing the public health burden of antimicrobial resistance.
| S-EPMC6030107 | biostudies-literature
Project description:Colistin is one of the last-resort antibiotics for infections caused by multidrug-resistant Gram-negative bacteria. However, the wide spread of novel plasmid-carrying colistin resistance genes mcr-1 and its variants substantially compromise colistin's therapeutic effectiveness and pose a severe danger to public health. To detect colistin-resistant microorganisms induced by mcr genes, rapid and reliable antibiotic susceptibility testing (AST) is imminently needed. In this study, we identified an RNA-based AST (RBAST) to discriminate between colistin-susceptible and mcr-1-mediated colistin-resistant bacteria. After short-time colistin treatment, RBAST can detect differentially expressed RNA biomarkers in bacteria. Those candidate mRNA biomarkers were successfully verified within colistin exposure temporal shifts, concentration shifts, and other mcr-1 variants. Furthermore, a group of clinical strains were effectively distinguished by using the RBAST approach during the 3-h test duration with over 93% accuracy. Taken together, our findings imply that certain mRNA transcripts produced in response to colistin treatment might be useful indicators for the development of fast AST for mcr-positive bacteria. IMPORTANCE The emergence and prevalence of mcr-1 and its variants in humans, animals, and the environment pose a global public health threat. There is a pressing urgency to develop rapid and accurate methods to identify MCR-positive colistin-resistant bacteria in the clinical samples, providing a basis for subsequent effective antibiotic treatment. Using the specific mRNA signatures, we develop an RNA-based antibiotic susceptibility testing (RBAST) for effectively distinguishing colistin-susceptible and mcr-1-mediated colistin-resistant strains. Meanwhile, the detection efficiency of these RNA biomarkers was evidenced in other mcr variants-carrying strains. By comparing with the traditional AST method, the RBAST method was verified to successfully characterize a set of clinical isolates during 3 h assay time with over 93% accuracy. Our study provides a feasible method for the rapid detection of colistin-resistant strains in clinical practice.
| S-EPMC9241874 | biostudies-literature
Project description:This study investigated the characteristics of Escherichia coli isolates carrying mcr-1-blaNDM from a chicken farm in China. Of the 78 E. coli isolates, 21 clonally unrelated isolates carried mcr-1-blaNDM Diverse IncI2 plasmids disseminated mcr-1, while the dissemination of blaNDM was mediated by diverse IncB/O plasmids. More striking was the colocalization of resistance genes mcr-1 and blaNDM-4 in an IncHI2/ST3 plasmid, which might pose a great challenge for public health.
| S-EPMC5328528 | biostudies-other
Project description:Antibiotic-resistant Escherichia coli is one of the most serious problems in pig production. This study aimed to determine the antibiotic susceptibility and genotypes profiles of diarrhoeagenic E. coli that causes diarrhea in piglets. Thirty-seven pathogenic E. coli strains were used in this study. These were isolated from rectal swabs of diarrheic piglets from farms in Thailand from 2018 to 2019. Escherichia coli isolates were highly resistant to amoxicillin (100%), followed by oxytetracycline (91.9%), enrofloxacin (89.2%), trimethoprim/sulfamethoxazole (86.5%), amoxicillin: clavulanic acid (81.1%), colistin and gentamicin (75.7%), ceftriaxone and ceftiofur (64.9%), ceftazidime (35.1%) and 97.3% showed multidrug-resistance (MDR). There were 8 (21.6%) mcr-1 carriers, 10 (27.0%) mcr-3 carriers and 10 (27.0%) co-occurrent mcr-1 and mcr-3 isolates. The phenotype-genotype correlation of colistin resistance was statistically significant (performed using Cohen's kappa coefficient (κ = 0.853; p < 0.001)). In addition, PCR results determined that 28 of 37 (75.7%) isolates carried the int1 gene, and 85.7% int1-positive isolates also carried the mcr gene. Genetic profiling of E. coli isolates performed by ERIC-PCR showed diverse genetics, differentiated into thirteen groups with 65% similarity. Knowledge of the molecular origins of multidrug-resistant E. coli should be helpful for when attempting to utilize antibiotics in the pig industry. In terms of public health awareness, the possibility of transmitting antibiotic-resistant E. coli from diarrheic piglets to other bacteria in pigs and humans should be of concern.
| S-EPMC9156692 | biostudies-literature
Project description:ObjectiveHere, we report a case of severe infection caused by Escherichia coli that harbored mcr-1, bla NDM-5, and acquired resistance to tigecycline during tigecycline salvage therapy.MethodsAntimicrobial susceptibility testing, Southern blot hybridization, and complete genome sequence of the strains were carried out. The genetic characteristics of the mcr-1 and bla NDM-5 plasmids were analyzed. The whole genome sequencing of mcr-1-containing plasmid was completed. Finally, putative single nucleotide polymorphisms and deletion mutations in the tigecycline-resistant strain were predicted.ResultsThree E. coli isolates were obtained from ascites, pleural effusion, and stool of a patient; they were resistant to almost all the tested antibiotics. The first two strains separated from ascites (E-FQ) and hydrothorax (E-XS) were susceptible to amikacin and tigecycline; however, the third strain from stool (E-DB) was resistant to tigecycline after nearly 3 weeks' treatment with tigecycline. All three isolates possessed both mcr-1 and bla NDM-5. The bla NDM-5 gene was found on the IncX3 plasmid, whereas the mcr-1, fosA3 and blaCTX-M-14 were located on the IncHI2 plasmid. Mutations in acrB and lon were the reason for the resistance to tigecycline.ConclusionThis is the first report of a colistin-, carbapenem-, and tigecycline-resistant E. coli in China. Tigecycline resistance acquired during tigecycline therapy is of great concern for us because tigecycline is a drug of last resort to treat carbapenem-resistant Gram-negative bacterial infections. Furthermore, the transmission of such extensively drug-resistant isolates may pose a great threat to public health.
| S-EPMC6239116 | biostudies-literature