scholarly journals Evaluation of the AusDiagnostics MT CRE EU assay for the detection of carbapenemase genes and transferable colistin resistance determinants mcr-1/-2 in MDR Gram-negative bacteria

2018 ◽  
Author(s):  
Danièle Meunier ◽  
Neil Woodford ◽  
Katie L Hopkins
Keyword(s):  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Resistance Determinants

scholarly journals Novel Plasmid-Mediated Colistin Resistance Gene mcr-3 in Escherichia coli

mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
Wenjuan Yin ◽  
Hui Li ◽  
Yingbo Shen ◽  
Zhihai Liu ◽  
Shaolin Wang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Resistance Gene ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
E Coli ◽  
Resistance Determinants ◽  
Phosphoethanolamine Transferases

ABSTRACT The mobile colistin resistance gene mcr-1 has attracted global attention, as it heralds the breach of polymyxins, one of the last-resort antibiotics for the treatment of severe clinical infections caused by multidrug-resistant Gram-negative bacteria. To date, six slightly different variants of mcr-1, and a second mobile colistin resistance gene, mcr-2, have been reported or annotated in the GenBank database. Here, we characterized a third mobile colistin resistance gene, mcr-3. The gene coexisted with 18 additional resistance determinants in the 261-kb IncHI2-type plasmid pWJ1 from porcine Escherichia coli. mcr-3 showed 45.0% and 47.0% nucleotide sequence identity to mcr-1 and mcr-2, respectively, while the deduced amino acid sequence of MCR-3 showed 99.8 to 100% and 75.6 to 94.8% identity to phosphoethanolamine transferases found in other Enterobacteriaceae species and in 10 Aeromonas species, respectively. pWJ1 was mobilized to an E. coli recipient by conjugation and contained a plasmid backbone similar to those of other mcr-1-carrying plasmids, such as pHNSHP45-2 from the original mcr-1-harboring E. coli strain. Moreover, a truncated transposon element, TnAs2, which was characterized only in Aeromonas salmonicida, was located upstream of mcr-3 in pWJ1. This ΔTnAs2-mcr-3 element was also identified in a shotgun genome sequence of a porcine E. coli isolate from Malaysia, a human Klebsiella pneumoniae isolate from Thailand, and a human Salmonella enterica serovar Typhimurium isolate from the United States. These results suggest the likelihood of a wide dissemination of the novel mobile colistin resistance gene mcr-3 among Enterobacteriaceae and aeromonads; the latter may act as a potential reservoir for mcr-3. IMPORTANCE The emergence of the plasmid-mediated colistin resistance gene mcr-1 has attracted substantial attention worldwide. Here, we examined a colistin-resistant Escherichia coli isolate that was negative for both mcr-1 and mcr-2 and discovered a novel mobile colistin resistance gene, mcr-3. The amino acid sequence of MCR-3 aligned closely with phosphoethanolamine transferases from Enterobacteriaceae and Aeromonas species originating from both clinical infections and environmental samples collected in 12 countries on four continents. Due to the ubiquitous profile of aeromonads in the environment and the potential transfer of mcr-3 between Enterobacteriaceae and Aeromonas species, the wide spread of mcr-3 may be largely underestimated. As colistin has been and still is widely used in veterinary medicine and used at increasing frequencies in human medicine, the continuous monitoring of mobile colistin resistance determinants in colistin-resistant Gram-negative bacteria is imperative for understanding and tackling the dissemination of mcr genes in both the agricultural and health care sectors. IMPORTANCE The emergence of the plasmid-mediated colistin resistance gene mcr-1 has attracted substantial attention worldwide. Here, we examined a colistin-resistant Escherichia coli isolate that was negative for both mcr-1 and mcr-2 and discovered a novel mobile colistin resistance gene, mcr-3. The amino acid sequence of MCR-3 aligned closely with phosphoethanolamine transferases from Enterobacteriaceae and Aeromonas species originating from both clinical infections and environmental samples collected in 12 countries on four continents. Due to the ubiquitous profile of aeromonads in the environment and the potential transfer of mcr-3 between Enterobacteriaceae and Aeromonas species, the wide spread of mcr-3 may be largely underestimated. As colistin has been and still is widely used in veterinary medicine and used at increasing frequencies in human medicine, the continuous monitoring of mobile colistin resistance determinants in colistin-resistant Gram-negative bacteria is imperative for understanding and tackling the dissemination of mcr genes in both the agricultural and health care sectors.

scholarly journals Formation in vitro of colistin resistance in carbapenem-resistant Gram-negative bacteria and its biological cost

2021 ◽  
Author(s):  
D. V. Tapalski ◽  
T. A. Petrovskaya ◽  
A. E. Kozlov
Keyword(s):  
Broth Culture ◽  
Exponential Growth Phase ◽  
Lag Phase ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Broth Microdilution Method ◽  
Resistant Mutants ◽  
Biological Cost

Introduction. The spread of resistance to carbapenems among gram-negative bacteria have led to an increase in the consumption of polymyxins and the emergence of certain strains resistant to them. Polymyxin resistance is mainly associated with mutations in chromosomal genes. The development of mutational resistance to antibiotics can lead to a decrease in the viability of bacteria, which is manifested by an increase in the duration of the cell cycle, a decrease in virulence and competitive fitness. The purpose of the study was to assess in vitro the intensity of the formation of colistin resistance in carbapenemresistant clinical isolates of gram-negative bacteria, the stability of the formed emerged resistance and its biological cost.Materials and methods. For 46 strains of Klebsiella pneumoniae, 77 strains of Pseudomonas aeruginosa and 42 strains of Acinetobacter baumannii, real time polymerase chain reaction (PCR) was used to detect the genes of carbapenemases, the minimum inhibitory concentrations (MIC) of meropenem and colistin were determined by broth microdilution method. The selection of resistant subpopulations on Muller–Hinton agar with the addition of 16 mg/l colistin was carried out. For colistin-resistant mutants and their isogenic sensitive strains, the kinetic parameters of growth in broth culture were determined. Incubation and result recording were performed on an Infinite M200 microplate reader for 18.5 hours at 35°C with measurement of light scatter in the wells every 15 minutes.Results. The production of carbapenemases MBL VIM in P. aeruginosa, MBL NDM, KPC and OXA-48 in K. pneumoniae, OXA-23 and OXA-40 in A. baumannii was observed. All strains were sensitive to colistin (MIC varied from 0.062 to 2 mg/l). The colony growth on a selective medium with16 mg/l colistin was observed for 97.8% of K. pneumoniae strains, 16.9% of P. aeruginosa strains, and 61.9% of A. baumannii strains. The mutational nature of colistin resistance was confirmed for 21.7% of K. pneumoniae strains. For colistin-resistant mutants of K. pneumoniae, a significant increase in the duration of the lag phase (Tlag) was observed: 225.6 ± 7.037 min in the wild-type susceptible strains and 245.5 ± 8.726 in resistant mutants, p = 0.037. The indicators of the doubling time of the number of microbial cells in the exponential growth phase (Tdoubling) and the area under the bacterial growth curve did not differ significantly.Conclusion. A high frequency of formation of colistin resistance in vitro in carbapenemase-producing strains of K. pneumoniae was observed. The absence of significant changes in the kinetics of microbial growth in resistant strains makes it possible to predict the further spread of mutational resistance to colistin, as well as its preservation in microbial populations of K. pneumoniae even in the case of limiting the use of this antibiotic. 

scholarly journals Emergence of Colistin Resistant Gram-Negative Bacteria in a Tertiary Care Rural Hospital in 2019

KYAMC Journal ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 87-90
Author(s):  
Abdullah Akhtar Ahmed ◽  
Nusrat Akhtar Juyee ◽  
SM Ali Hasan
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Tertiary Care ◽  
Salmonella Typhi ◽  
Rural Hospital ◽  
Gram Negative Bacteria ◽  
Bacterial Isolates ◽  
Colistin Resistance ◽  
Sensitivity Testing ◽  
Gram Negative

Background: Colistin-resistant Gram-negative bacteria is a rapidly emerging global threatgenerated a sense of public alarm. Objective: To combat this challenge a study was designedto evaluate the fast spreading infections by colistin-resistant pathogens in the tertiary care rural hospital of Bangladesh. Materials and Methods: To study isolation ofpathogenic gram-negative bacilli,clinical sample (n-640) of hospitalized patients of Khwaja Yunus Ali Medical College Hospital in Enayetpur, Bangladesh during the 1st quarter of the year 2019 were used. The bacterial isolates were screened for meropenem and colistin-resistance. Results: A total of 156 bacterial isolates were studied which included Escherichia coli (n-112), Klebsiella pneumoniae (n-14), Pseudomonas aeruginosa (n-27), and Salmonella typhi (n-3). Antibiotic sensitivity testing showed that 32/156(20%) and 119/156 (76%) isolates were resistant to meropenem and colistin, respectively. whereas 50/156 (32%) isolates were resistant to both antibiotics. Escherichia coli, K. pneumoniae, pseudomonas aeruginosa, and Salmonella typhi isolates respectivelywere 112/156 (72%), 14/156 (9%). 27/156 (17%), and 3/156 (2%). Conclusion: Colistin is typically used as salvage therapy, or last-line treatment, for MDR gramnegative infections.But there is worrisome therapeutic scenario in our study finding of colistin resistance is 76% in Gram-negative bacteria of the clinical isolates. The restricted and rational use of colistin drug is the need of hour. KYAMC Journal Vol. 11, No.-2, July 2020, Page 87-90

scholarly journals Heterogeneous and Flexible Transmission ofmcr-1in Hospital-AssociatedEscherichia coli

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Yingbo Shen ◽  
Zuowei Wu ◽  
Yang Wang ◽  
Rong Zhang ◽  
Hong-Wei Zhou ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Genomic Analysis ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Genes Encoding

ABSTRACTThe recent emergence of a transferable colistin resistance mechanism, MCR-1, has gained global attention because of its threat to clinical treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, the possible transmission route ofmcr-1amongEnterobacteriaceaespecies in clinical settings is largely unknown. Here, we present a comprehensive genomic analysis ofEscherichia coliisolates collected in a hospital in Hangzhou, China. We found thatmcr-1-carrying isolates from clinical infections and feces of inpatients and healthy volunteers were genetically diverse and were not closely related phylogenetically, suggesting that clonal expansion is not involved in the spread ofmcr-1. Themcr-1gene was found on either chromosomes or plasmids, but in most of theE. coliisolates,mcr-1was carried on plasmids. The genetic context of the plasmids showed considerable diversity as evidenced by the different functional insertion sequence (IS) elements, toxin-antitoxin (TA) systems, heavy metal resistance determinants, and Rep proteins of broad-host-range plasmids. Additionally, the genomic analysis revealed nosocomial transmission ofmcr-1and the coexistence ofmcr-1with other genes encoding β-lactamases and fluoroquinolone resistance in theE. coliisolates. These findings indicate thatmcr-1is heterogeneously disseminated in both commensal and pathogenic strains ofE. coli, suggest the high flexibility of this gene in its association with diverse genetic backgrounds of the hosts, and provide new insights into the genome epidemiology ofmcr-1among hospital-associatedE. colistrains.IMPORTANCEColistin represents one of the very few available drugs for treating infections caused by extensively multidrug-resistant Gram-negative bacteria. The recently emergentmcr-1colistin resistance gene threatens the clinical utility of colistin and has gained global attention. Howmcr-1spreads in hospital settings remains unknown and was investigated by whole-genome sequencing ofmcr-1-carryingEscherichia coliin this study. The findings revealed extraordinary flexibility ofmcr-1in its spread among genetically diverseE. colihosts and plasmids, nosocomial transmission ofmcr-1-carryingE. coli, and the continuous emergence of novel Inc types of plasmids carryingmcr-1and newmcr-1variants. Additionally,mcr-1was found to be frequently associated with other genes encoding β-lactams and fluoroquinolone resistance. These findings provide important information on the transmission and epidemiology ofmcr-1and are of significant public health importance as the information is expected to facilitate the control of this significant antibiotic resistance threat.

scholarly journals Virulence Determinants and Plasmid-Mediated Colistin Resistance mcr Genes in Gram-Negative Bacteria Isolated From Bovine Milk

2021 ◽  
Vol 11 ◽  
Author(s):  
Yasmine H. Tartor ◽  
Rasha M. A. Gharieb ◽  
Norhan K. Abd El-Aziz ◽  
Hend M. El Damaty ◽  
Shymaa Enany ◽  
...  
Keyword(s):  
Virulence Genes ◽  
Raw Milk ◽  
Subclinical Mastitis ◽  
Clinical Mastitis ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Genetic Characteristics ◽  
Gram Negative ◽  
E Coli ◽  
Resistant Strains

A major increase of bacterial resistance to colistin, a last-resort treatment for severe infections, was observed globally. Using colistin in livestock rearing is believed to be the ground of mobilized colistin resistance (mcr) gene circulation and is of crucial concern to public health. This study aimed to determine the frequency and virulence characteristics of colistin-resistant Gram-negative bacteria from the milk of mastitic cows and raw unpasteurized milk in Egypt. One hundred and seventeen strains belonging to Enterobacteriaceae (n = 90), Pseudomonas aeruginosa (n = 10), and Aeromonas hydrophila (n = 17) were screened for colistin resistance by antimicrobial susceptibility testing. The genetic characteristics of colistin-resistant strains were investigated for mcr-1–9 genes, phylogenetic groups, and virulence genes. Moreover, we evaluated four commonly used biocides in dairy farms for teat disinfection toward colistin-resistant strains. Multidrug-resistant (MDR) and extensive drug-resistant (XDR) phenotypes were detected in 82.91% (97/117) and 3.42% (4/117) of the isolates, respectively. Of the 117 tested isolates, 61 (52.14%) were colistin resistant (MIC >2 mg/L), distributed as 24/70 (34.29%) from clinical mastitis, 10/11 (90.91%) from subclinical mastitis, and 27/36 (75%) from raw milk. Of these 61 colistin-resistant isolates, 47 (19 from clinical mastitis, 8 from subclinical mastitis, and 20 from raw milk) harbored plasmid-borne mcr genes. The mcr-1 gene was identified in 31.91%, mcr-2 in 29.79%, mcr-3 in 34.04%, and each of mcr-4 and mcr-7 in 2.13% of the colistin-resistant isolates. Among these isolates, 42.55% (20/47) were E. coli, 21.28% (10/47) A. hydrophila, 19.12% (9/47) K. pneumoniae, and 17.02% (8/47) P. aeruginosa. This is the first report of mcr-3 and mcr-7 in P. aeruginosa. Conjugation experiments using the broth-mating technique showed successful transfer of colistin resistance to E. coli J53-recipient strain. Different combinations of virulence genes were observed among colistin-resistant isolates with almost all isolates harboring genes. Hydrogen peroxide has the best efficiency against all bacterial isolates even at a low concentration (10%). In conclusion, the dissemination of mobile colistin resistance mcr gene and its variants between MDR- and XDR-virulent Gram-negative isolates from dairy cattle confirms the spread of mcr genes at all levels; animals, humans, and environmental, and heralds the penetration of the last-resort antimicrobial against MDR bacteria. Consequently, a decision to ban colistin in food animals is urgently required to fight XDR and MDR bacteria.

scholarly journals Investigating colistin drug resistance: The role of high-throughput sequencing and bioinformatics

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 150 ◽  
Author(s):  
Dickson Aruhomukama ◽  
Ivan Sserwadda ◽  
Gerald Mboowa
Keyword(s):  
Antibiotic Resistance ◽  
High Throughput ◽  
Bacterial Infections ◽  
High Throughput Sequencing ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Colistin Resistance ◽  
Gram Negative

Bacterial infections involving antibiotic resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR) or extensive drug resistant (XDR) bacterial strains. Most recently, a novel acquired plasmid mediated resistance mechanism to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR and XDR gram-negative bacteria, has been reported. Plasmid mediated colistin resistant gram-negative bacteria have been described to be pan-drug resistant, implying a state devoid of alternative antibiotic therapeutic options. This review describes the evolution of antibiotic resistance to plasmid mediated colistin resistance, and discusses the potential role of high-throughput sequencing technologies, genomics and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antimicrobial resistance as a whole.

scholarly journals Combining Colistin with Furanone C-30 Rescues Colistin Resistance of Gram-Negative Bacteria in Vitro and in Vivo

2021 ◽  
Author(s):  
Ying Zhang ◽  
Yishuai Lin ◽  
Xiaodong Zhang ◽  
Liqiong Chen ◽  
Chunyan Xu ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
C 30

Colistin is among the few antibiotics effective against multidrug-resistant Gram-negative bacteria (GNB) clinical isolates. However, colistin-resistant GNB strains have emerged in recent years.

scholarly journals Recent progress on elucidating the molecular mechanism of plasmid-mediated colistin resistance and drug design

2019 ◽  
Vol 23 (3) ◽  
pp. 355-366 ◽  
Author(s):  
Jindan Kai ◽  
Sheng Wang
Keyword(s):  
Drug Design ◽  
Recent Progress ◽  
Lipid A ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Global Challenge ◽  
Enzymatic Mechanism ◽  
Inner Membrane Protein

AbstractAntibiotic resistance is a growing global challenge to public health. Polymyxin is considered to be the last-resort antibiotic against most gram-negative bacteria. Recently, discoveries of a plasmid-mediated, transferable mobilized polymyxin resistance gene (mcr-1) in many countries have heralded the increased threat of the imminent emergence of pan-drug-resistant super bacteria. MCR-1 is an inner membrane protein that enables bacteria to develop resistance to polymyxin by transferring phosphoethanolamine to lipid A. However, the mechanism associated with polymyxin resistance has yet to be elucidated, and few drugs exist to address this issue. Here, we review our current understanding regarding MCR-1 and small molecule inhibitors to provide a detailed enzymatic mechanism of MCR-1 and the associated implications for drug design.

Sign in / Sign up

Export Citation Format

Share Document