Escherichia coli and their potential transmission of carbapenem and colistin-resistant genes in camels
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ABSTRACT:
SUBMITTER: youseef M
PROVIDER: S-EPMC10893666 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:The purpose was to explore the optimal dosage regimen of colistin using Monte Carlo simulations, for the treatment of carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli based on PK/PD targets in critically ill patients. A total of 116 carbapenem-resistant K. pneumoniae and E. coli were obtained from various clinical specimens at Siriraj Hospital in Bangkok, Thailand. Minimum inhibitory concentrations (MICs) of colistin were determined by broth microdilution method. Monte Carlo simulation was used to calculate the cumulative fraction of response (CFR) for European Medicine Agency (EMA), US-Food and Drug Administration (FDA), Nation et al., Siriraj Hospital and our study regimens. The targeted CFR was 90%. For colistin-susceptible K. pneumoniae, all of the dosage regimens achieved ≥90% CFR in patients with creatinine clearance <80 mL/min except the FDA-approved regimens for patients with creatinine clearance 51-79 and 11-29 mL/min, respectively. While, patients with creatinine clearance ≥80 mL/min, CFR ≥90% was observed in Siriraj Hospital and our study regimen. For colistin-susceptible E. coli, all of the dosage regimens achieved ≥90% CFR regardless of renal function. In contrast, the currently approved regimens achieved CFR target in only 10-50% for colistin-resistant isolates subgroup. These results suggest that currently approved regimens still recommended for colistin-susceptible CRE. For colistin-resistant CRE, alternative approaches such as high dose or combination therapy should be considered.
| S-EPMC6784242 | biostudies-literature
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.
| S-EPMC6920953 | biostudies-literature
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:Background:Bacterial infections have become more challenging to treat due to the emergence of multidrug-resistant pathogenic bacteria. Combined antibiotics prove to be a relatively effective method to control such resistant strains. This study aim to investigate synergistic activity of eugenol combined with colistin against a collection of clinical isolated Escherichia coli (E.coli) strains, and to evaluate potential interaction. Methods:Antimicrobial susceptibility, minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI) of the bacteria were determined by disk diffusion assay, broth microdilution method and checkerboard assay, respectively. The mcr-1 mRNA expression was measured by Real-time PCR. To predict possible interactions between eugenol and MCR-1, molecular docking assay was taken. Results:For total fourteen strains including eight colistin-resistant strains, eugenol was determined with MIC values of 4 to 8 μg/mL. Checkerboard dilution test suggested that eugenol exhibited synergistic activity when combined with colistin (FICI ranging from 0.375 to 0.625). Comparison analysis of Real-time PCR showed that synergy could significantly down-regulate expression of mcr-1 gene. A metal ion coordination bond with catalytic zinc atom and a hydrogen bond with crucial amino acid residue Ser284 of MCR-1 were observed after molecular docking, indicating antibacterial activity and direct molecular interactions of eugenol with MCR-1 protein. Conclusions:Our results demonstrated that eugenol exhibited synergistic effect with colistin and enhanced its antimicrobial activity. This might further contribute to the antibacterial actions against colistin-resistant E.coli strains.
| S-EPMC5789579 | biostudies-literature
Project description:Escherichia coli is a leading cause of nosocomial infections. Carbapenem-resistant E. coli (CREC), which has been frequently isolated in recent years because of the widespread use of carbapenems, poses a significant challenge to clinical anti-infection treatment. In this study, a total of 27 CREC strains were identified from a set of 795 E. coli isolates collected over a two-year period from a tertiary hospital in China. Whole-genome sequencing revealed that 17 strains carried the bla NDM-5 gene, 5 strains carried the bla NDM-1 gene, 1 strain carried the bla NDM-7 gene, and the remaining 4 strains carried the bla KPC-2 gene. All 23 NDM-producing E. coli strains were resistant to all antibiotics except tigecycline, colistin, and cefiderocol. Nine different sequence types (STs) were identified, with ST410 and ST167 being the most prevalent. All of the bla NDM genes were located on conjugatable plasmids. We identified five different plasmid replicon types ranging in size from 20 kb to 200 kb, with the IncX3-type plasmid, 46 kb in size, being a key factor in facilitating the horizontal transmission of the bla NDM gene in E. coli. The structure surrounding the bla NDM gene was relatively conserved and mainly contained the following structures: IS3000-ISAbal25-IS5-bla NDM-ble MBL-trpF-dsbC-IS26. However, the plasmid backbone structure was highly variable, which indicates that the bla NDM gene has already spread horizontally among different types of plasmids. In addition, we discovered two copies of the bla NDM-5 gene in a single plasmid (pEC29-NDM-5), with an identical structure around the gene and the complete sequence of the class 1 integron. Our findings detail the prevalence of CREC in a tertiary hospital in China, and the emergence of multiple copies of the bla NDM-5 gene on a single plasmid needs our attention.
| S-EPMC9842800 | biostudies-literature
Project description: Not available
| S-EPMC6067848 | biostudies-literature
Project description:The surveillance of mobile genetic elements facilitating the spread of antimicrobial resistance genes has been challenging. Here, we tracked both clonal and plasmid transmission in colistin- and carbapenem-resistant Klebsiella pneumoniae using short- and long-read sequencing technologies. We observed three clonal transmissions, all containing Incompatibility group (Inc) L plasmids and New Delhi metallo-beta-lactamase blaNDM-1, although not co-located on the same plasmid. One IncL-blaNDM-1 plasmid had been transferred between sequence type (ST) 392 and ST15, and the promiscuous IncL-blaOXA-48 plasmid was likely shared between a singleton and a clonal transmission of ST392. Plasmids within clonal outbreaks and between clusters and STs had 0-2 single nucleotide polymorphism (SNP) differences, showing high stability upon transfer to same or different STs. The simplest explanation, without a comprehensive analysis with long-read sequencing, would be the spread of a single common IncL-blaNDM-1 plasmid. However, here, we report blaNDM-1 in five different plasmids, emphasizing the need to investigate plasmid-mediated transmission for effective containment of outbreaks.IMPORTANCEAntimicrobial resistance occupies a central stage in global public health emergencies. Recently, efforts to track the genetic elements that facilitate the spread of resistance genes in plasmids outbreaks, utilizing short-read sequencing technologies, have been described. However, incomplete plasmid reconstruction from short-read sequencing data hinders full knowledge about plasmid structure, which makes the exploration very challenging. In this study, we used both short- and long-read sequencing in clinical Klebsiella pneumoniae from University Hospital Centre Zagreb, Croatia, which was resistant to both last-resort antibiotics colistin and carbapenem. Our results show complex transmission networks and sharing of plasmids, emphasizing multiple transmissions of plasmids harboring carbapenem and/or colistin resistance genes between and within K. pneumoniae clones. Only full-length sequencing plus a novel way of determining plasmid clusters resulted in the complete picture, showing how future active monitoring of plasmids as a vital tool for infection prevention and control could be implemented.
| S-EPMC11834398 | biostudies-literature
Project description:Colistin resistance has increased due to the increasing and inappropriate use of this antibiotic. The mechanism involves modification of lipid A with phosphoethanolamine (PEtN) and/or 4-amino-4deoxy-L-arabinose (L-Ara4N). EptA and eptB catalyze the transfer of phosphoethanolamine to lipid A. In this study, gene network was constructed to find the associated genes related to colistin resistance, and further in vitro validation by transcriptional analysis was performed. In silico studies showed that eptB gene is a highly interconnected node in colistin resistance gene network. To ascertain these findings twelve colistin-resistant clinical isolates of Escherichia coli were selected in which five were harboring the plasmid-mediated mcr-1. Screening for colistin resistance was performed by broth microdilution (BMD) method and Rapid polymyxin NP test. PCR confirmed the presence of the eptA and eptB genes in all isolates and five isolates were harboring mcr-1. Transcriptional expression in five isolates harboring mcr-1, showed an enhanced expression of eptB when exposed under sub-inhibitory colistin stress. The present study for the first time highlighted genetic interplay between mcr-1 and eptA and eptB under colistin exposure.
| S-EPMC8789769 | biostudies-literature
Project description:Colistin-resistant Escherichia coli are isolated from pigs suffering from post-weaning diarrhea (PWD). This study was designed to develop an experimental model of PWD using mcr-1-carrying shiga toxin-producing E. coli (STEC) or enterotoxigenic E. coli (ETEC), for the future evaluation of control measures. Three groups of eight piglets, kept in high biosecurity units, were orally inoculated with mcr-1-positive STEC or ETEC, and one unchallenged group was used as a control. Clinical signs were recorded. Regularly-collected fecal samples and samples obtained from the digestive tract of animals sacrificed one month after inoculation were cultured in selective media and isolates were characterized. Blood samples were used to genotype the polymorphisms of the pigs' intestinal receptors for F4 and F18 E. coli adhesins. Diarrhea was more frequent and more fecal samples contained the inoculated strain in the group inoculated with the O149-F4 ETEC strain than with the O141-F18 or O139-F18 STEC strains. However, fewer positive samples were obtained from the two pigs with the F4 resistant genotype. The three inoculated strains could be re-isolated up to the end of the experiment. Excretion peaked on the first week after inoculation with the O149-F4 ETEC strain, and later for the other two. An mcr-1 gene transfer to other commensal isolates was observed only for O139-F18 STEC, while the loss of mcr-1 from the inoculated strain occurred in all groups. The O149-F4 ETEC challenge may be used to evaluate alternative solutions to combat PWD caused by colistin-resistant E. coli in pigs.
| S-EPMC7126850 | biostudies-literature
Project description: Not available
| S-EPMC5365728 | biostudies-literature