scholarly journals Regional Dissemination of a Carbapenemase-encoding Plasmid: Plasmidome analysis Reveals Diverse Adaptations of Carbapenemase-Producing Enterobacteriaceae

2020 ◽  
Author(s):  
Ryuichiro Abe ◽  
Yukihiro Akeda ◽  
Yo Sugawara ◽  
Dan Takeuchi ◽  
Yuki Matsumoto ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Single Point ◽  
Complete Sequence ◽  
Surveillance Study ◽  
Single Point Mutation ◽  
Chromosomal Integration ◽  
Carbapenemase Gene ◽  
Resistance Patterns ◽  
Horizontal Spread

Abstract Background. The global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) threatens human health by limiting the range of usable antibiotics even against common bacterial infections. The spread of CRE is primarily due to the transmission of carbapenemase genes located on plasmids. However, few studies have comprehensively identified regionally spreading carbapenemase-encoding plasmids because of the difficulty to determine the complete sequence of a plasmid encoding carbapenemases. In a CRE surveillance study of 1,507 patients from 43 hospitals in northern Osaka, Japan, we previously found that 12% of the patients carried CRE and 95% of CRE isolates were IMP-6 producers. This result suggested a vast horizontal spread of a clonal plasmid carrying blaIMP-6 among Enterobacteriaceae in this region. In the current study, we aimed to describe the dynamics of this regional horizontal plasmid transmission.Results. We systematically analysed the plasmids of 230 CRE isolates carrying blaIMP obtained in our previous surveillance study by using whole genome sequencing and Southern blotting. We detected a major population (187 out of 230 blaIMP-positive CRE isolates, 85.6%) that carried blaIMP-6 on the IncN plasmid pKPI-6, along with diverse minor subpopulations. Among the subpopulations, we identified a novel cluster carrying an IncF plasmid that leads to heteroresistance due to amplification of blaIMP-6, resulting in covert transmission of blaIMP-6 or occasional chromosomal integration of blaIMP-6. In addition, we detected one isolate that harboured blaIMP-1, which is identical to blaIMP-6 except for a single point mutation, on pKPI-6 and thus had acquired a broader range of antimicrobial resistance. Conclusions. Carbapenemase-encoding plasmid tracking revealed the clonal dissemination of pKPI-6 among chromosomally distinct isolates. Focusing on the mode of carbapenemase gene carriage is helpful for monitoring of horizontal spread of CRE isolates that is difficult to trace only by the comparisons of the whole genomes. A seemingly clonal horizontal dissemination of the predominant plasmid had embraced heterogenous subpopulations that contribute to diverse adaptations including covert transmission, stable chromosomal integration of blaIMP-6, or broadened antimicrobial resistance patterns, ultimately leading to treatment failure.

scholarly journals Characterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant Enterobacteriaceae

mSystems ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Ryuichiro Abe ◽  
Yukihiro Akeda ◽  
Yo Sugawara ◽  
Dan Takeuchi ◽  
Yuki Matsumoto ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Antimicrobial Resistance ◽  
Point Mutation ◽  
Bacterial Infections ◽  
Bacterial Species ◽  
Single Point ◽  
Single Point Mutation ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Whole Genomes

ABSTRACT Carbapenem-resistant Enterobacteriaceae (CRE) infections, high in morbidity and mortality, pose serious clinical challenges due to limited treatment options. A previous CRE surveillance study on 1,507 patients from 43 hospitals in Osaka, Japan, revealed that 12% of patients carried CRE and that 95% of the CRE isolates were IMP-type carbapenemase producers. Here, the mechanisms for this regional dissemination of a single carbapenemase gene were investigated. Since the dissemination of CRE is primarily due to the transmission of carbapenemase genes located on plasmids, we analyzed the plasmidome of 230 CRE isolates carrying blaIMP by whole-genome sequencing and Southern blotting. blaIMP-6 was found to be predominantly disseminated among chromosomally distinct isolates through the pKPI-6 plasmid. Underlying the vast clonal dissemination of pKPI-6, various subpopulations deriving from pKPI-6 were identified, which had acquired advantages for the dissemination of CRE isolates. A cluster exhibiting heteroresistance against meropenem by the transcriptional regulation of blaIMP-6 caused an outbreak likely through covert transmission of blaIMP-6. For stable carriage of blaIMP-6, they occasionally integrated blaIMP-6 on their chromosomes. In addition, we detected one isolate that broadened the range of antimicrobial resistance through a single point mutation in blaIMP-6 on pKPI-6. Multifaceted analysis of the plasmidome granted us more accurate perspectives on the horizontal spread of CRE isolates, which is difficult to trace only by comparing the whole genomes. This study revealed the predominant spread of a specific carbapenemase-encoding plasmid accompanying the emergence of phenotypically diverse derivatives, which may facilitate further dissemination of CRE in various environments. IMPORTANCE Global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) threatens human health by limiting the efficacy of antibiotics even against common bacterial infections. Carbapenem resistance, mainly due to carbapenemase, is generally encoded on plasmids and is spread across bacterial species by conjugation. Most CRE epidemiological studies have analyzed whole genomes or only contigs of CRE isolates. Here, plasmidome analysis on 230 CRE isolates carrying blaIMP was performed to shed light into the dissemination of a single carbapenemase gene in Osaka, Japan. The predominant dissemination of blaIMP-6 by the pKPI-6 plasmid among genetically distinct isolates was revealed, as well as the emergences of pKPI-6 derivatives that acquired advantages for further disseminations. Underlying vast clonal dissemination of a carbapenemase-encoding plasmid, heteroresistance was found in CRE offspring, which was generated by the transcriptional regulation of blaIMP-6, stabilization of blaIMP-6 through chromosomal integration, or broadened antimicrobial resistance due to a single point mutation in blaIMP-6.

scholarly journals Emerging Options for the Diagnosis of Bacterial Infections and the Characterization of Antimicrobial Resistance

2021 ◽  
Vol 22 (1) ◽  
pp. 456
Author(s):  
Simone Rentschler ◽  
Lars Kaiser ◽  
Hans-Peter Deigner
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Point Of Care ◽  
Rapid Identification ◽  
Adequate Treatment ◽  
Resistance Patterns ◽  
Detection And Diagnosis ◽  
Patient Prognosis ◽  
Point Of Care Detection

Precise and rapid identification and characterization of pathogens and antimicrobial resistance patterns are critical for the adequate treatment of infections, which represent an increasing problem in intensive care medicine. The current situation remains far from satisfactory in terms of turnaround times and overall efficacy. Application of an ineffective antimicrobial agent or the unnecessary use of broad-spectrum antibiotics worsens the patient prognosis and further accelerates the generation of resistant mutants. Here, we provide an overview that includes an evaluation and comparison of existing tools used to diagnose bacterial infections, together with a consideration of the underlying molecular principles and technologies. Special emphasis is placed on emerging developments that may lead to significant improvements in point of care detection and diagnosis of multi-resistant pathogens, and new directions that may be used to guide antibiotic therapy.

scholarly journals Evaluation of the impact of antimicrobial use protocols in PRRS virus infected swine on phenotypic antimicrobial resistance patterns

2021 ◽  
Author(s):  
Carissa A. Odland ◽  
Roy Edler ◽  
Noelle R. Noyes ◽  
Scott A. Dee ◽  
Joel Nerem ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Longitudinal Studies ◽  
Bacterial Infections ◽  
Population Level ◽  
Control Group ◽  
Antimicrobial Use ◽  
Treatment Groups ◽  
Resistance Patterns ◽  
The Impact ◽  
Over Time

A longitudinal study was conducted to assess the impact of different antimicrobial exposures of nursery-phase pigs on patterns of phenotypic antimicrobial resistance in fecal indicator organisms throughout the growing phase. Based on practical approaches used to treat moderate to severe PRRSV-associated secondary bacterial infections, two antimicrobial protocols of differing intensity of exposure [44.1 and 181.5 animal-treatment days per 1000 animal days at risk (ATD)] were compared with a control group with minimal antimicrobial exposure (2.1 ATD). Litter-matched pigs (n = 108) with no prior antimicrobial exposure were assigned randomly to the treatment groups. Pen fecal samples were collected nine times during the wean-to-finish period and cultured for Escherichia coli and Enterococcus spp. Antimicrobial susceptibility testing was conducted using NARMS gram-negative and gram-positive antibiotic panels. Despite up to 65-fold difference in ATD, few and modest differences were observed between groups and over time. Resistant patterns at marketing overall remained similar to those observed at weaning, prior to any antimicrobial exposures. Those differences observed could not readily be reconciled with the patterns of antimicrobial exposure. Resistance of E. coli to streptomycin was higher in the group exposed to 44.1 ATD, but no aminoglycosides were used. In all instances where resistance differed between time points, the higher resistance occurred early in the trial prior to any antimicrobial exposures. These minimal impacts on AMR despite substantially different antimicrobial exposures point to the lack of understanding of the drivers of AMR at the population level and the likely importance of factors other than antimicrobial exposure. IMPORTANCE Despite a recognized need for more longitudinal studies to assess the effects of antimicrobial use on resistance in food animals, they remain sparse in the literature, and most longitudinal studies of pigs have been observational. The current experimental study had the advantages of greater control of potential confounding, precise measurement of antimicrobial exposures which varied markedly between groups and tracking of pigs until market age. Overall, resistance patterns were remarkably stable between the treatment groups over time, and the differences observed could not be readily reconciled with the antimicrobial exposures, indicating the likely importance of other determinants of AMR at the population level.

scholarly journals Bacterial infections and emerging resistance in renal transplant recipients

2014 ◽  
Vol 14 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Inam Danish Khan ◽  
Ajay Kumar Sahni
Keyword(s):  
Renal Transplant ◽  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Tertiary Care ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Beta Lactamases ◽  
Post Transplant ◽  
Resistance Patterns ◽  
Altered Metabolism

Objective: Renal transplantation is frequently complicated by bacterial infections in the scenario of immunosuppression, altered metabolism and interventions resulting in prolonged morbidity. Subdued clinical presentation, antimicrobial resistance and toxicity question the outcome of transplantation. This retrospective study conducted at tertiary care apex transplant centre highlights colonization, clinical infection and antimicrobial resistance patterns in Renal Transplant Recipients (RTR). Materials and methods: Infection and antimicrobial resistance patterns in 130 RTR were studied. Clinico-demographic and transplant parameters were noted. Infection screening in the post transplant period along with antimicrobial susceptibility were used to analyze data in a post transplant time frame. Results and discussion: Culture positivity timeline was dominated by post surgical infections in the first week post transplant. Urinary infections followed by blood stream infections were noted. Infection profile included simultaneous polymicrobial, prolonged and widespread infections. Multi-resistant organisms producing beta lactamases and extended spectrum beta lactamases were isolated. Conclusion: Transplant recipients remain prone to bacterial infections with multi-resistant organisms which may persist due to immunosuppression, altered metabolism and toxicity, and contribute to nosocomial hazard. Infection control may be targeted at avoidance of donor derived infections, surgical complications, epidemiologic exposures, strengthening antimicrobial prophylaxis and anti-infection engineering. Antimicrobial stewardship, outbreak and epidemic preparedness should be ensured. DOI: http://dx.doi.org/10.3329/bjms.v14i1.16306 Bangladesh Journal of Medical Science Vol.14(1) 2015 p.14-21

scholarly journals An antibiotic-resistance conferring mutation in a neisserial porin: Structure, ion flux, and ampicillin binding

2020 ◽  
Author(s):  
A. Bartsch ◽  
C.M. Ives ◽  
C. Kattner ◽  
F. Pein ◽  
M. Diehn ◽  
...  
Keyword(s):  
Electric Fields ◽  
Bacterial Infections ◽  
Ion Selectivity ◽  
Single Point ◽  
Drug Binding ◽  
Single Point Mutation ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Beta Lactam ◽  
Gram Negative

ABSTRACTGram-negative bacteria cause the majority of highly drug-resistant bacterial infections. To cross the outer membrane of the complex Gram-negative cell envelope, antibiotics permeate through porins, trimeric channel proteins that enable the exchange of small polar molecules. Mutations in porins contribute to the development of drug-resistant phenotypes. In this work, we show that a single point mutation in the porin PorB from Neisseria meningitidis, the causative agent of bacterial meningitis, can strongly affect the binding and permeation of beta-lactam antibiotics. Using X-ray crystallography, high-resolution electrophysiology, atomistic biomolecular simulation, and liposome swelling experiments, we demonstrate differences in drug binding affinity, ion selectivity and drug permeability of PorB. Our work further reveals distinct interactions between the transversal electric field in the porin eyelet and the zwitterionic drugs, which manifest themselves under applied electric fields in electrophysiology and are altered by the mutation. These observations may apply more broadly to drug-porin interactions in other channels. Our results improve the molecular understanding of porin-based drug-resistance in Gram-negative bacteria.

Sign in / Sign up

Export Citation Format

Share Document