scholarly journals Novel mcr-3 variant, encoding mobile colistin resistance, in an ST131 Escherichia coli isolate from bloodstream infection, Denmark, 2014

2017 ◽  
Vol 22 (31) ◽  
Author(s):  
Louise Roer ◽  
Frank Hansen ◽  
Marc Stegger ◽  
Ute Wolff Sönksen ◽  
Henrik Hasman ◽  
...  

A novel variant of the plasmid-borne colistin resistance gene mcr-3 was detected on an IncHI2 plasmid in an ST131 CTX-M-55-producing Escherichia coli isolate from a Danish patient with bloodstream infection in 2014. The discovery of novel plasmid-borne genes conferring resistance to colistin is of special interest since colistin has reemerged as an important drug in the treatment of infections with multidrug-resistant Gram-negative bacteria.

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Yingbo Shen ◽  
Zuowei Wu ◽  
Yang Wang ◽  
Rong Zhang ◽  
Hong-Wei Zhou ◽  
...  

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.


Author(s):  
Xiaoyu Lu ◽  
Xia Xiao ◽  
Yuan Liu ◽  
Ruichao Li ◽  
Zhiqiang Wang

Tigecycline and colistin are used as last-resort therapies to treat infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, the emergence of the plasmid-mediated tigecycline resistance gene tet (X4) and the plasmid-mediated colistin resistance gene mcr-1 represents a significant threat to human health.


Author(s):  
M. Y. Iliyasu ◽  
I. Mustapha ◽  
H. Yakubu ◽  
H. M. Shuaibu ◽  
A. F. Umar ◽  
...  

Background of Study: Many virulence determinants contribute to the pathogenicity of Gram negative bacteria, like Escherichia coli, which is the most common cause of many infections worldwide such as urinary tract infection (UTI), profuse diarrhoea and septicaemia. Aim: To determine the genotypic characteristics of adhesin-producing E. coli isolates from clinical specimens. Place and Duration of Study: Conducted at the Infectious diseases hospital Bayara, Bauchi state, Nigeria, between February to March, 2019. Methods: A total of twelve (12) Gram negative bacterial isolates were selected based on the ability to grow on Luria-Bertani (LB) agar medium containing 100 µg/ml ampicillin. The isolates were from urine, stool, and blood specimens. The isolates were screened for multidrug resistant pattern according to Kirby-Bauer disc diffusion method. Adhesion factors, Fimbrial adhesin (fimH) and Invasive plasmid adhesin (ipaH) was genotyped by conventional PCR and sequenced. Results: All the isolates were resistant to Ampicillin, Cephalothin, Erythromycin, Fusidic acid, Novobiocin and Oxacillin, but sensitive to Augmentin, Colistin sulphate and Imipenem. Presence of fimH and ipaH genes were observed in nine isolates that expressed strong relationship with. Multidrug resistance (MDR). The fimH was the most prevalent found in urine, stool and blood isolates. Most of the adhesion genes sequence (61.8%) in this study had significant alignment (95 to 100% homology) with E.coli genome in the NCBI database. Conclusion: This study revealed the role of adhesin as virulence markers in MDR Gram negative bacteria and FimH is one of the commonest gene in MDR E.coli pathotypes.


KYAMC Journal ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 87-90
Author(s):  
Abdullah Akhtar Ahmed ◽  
Nusrat Akhtar Juyee ◽  
SM Ali Hasan

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


2021 ◽  
Author(s):  
Thomas T. Thomsen ◽  
Mette Kolpen ◽  
Vinoth Wigneswaran ◽  
Ulrik Kromann ◽  
Anna Ebbensgaard ◽  
...  

New antibiotics are needed against multidrug resistant Gram-negative pathogens that have compromised global health systems. Antimicrobial peptides are generally considered promising lead candidates for the next generation of antibiotics but have not fulfilled this expectation. Here we demonstrate activity of a cationic amphipathic undecapeptide (ChIP; Charge change Independent Peptide) against a wide panel of multidrug resistant Gram-negative pathogens. Importantly, the antimicrobial activity of ChIP is independent of the surface charge changes that confer colistin resistance through modification of Lipid A, while decreased activity of ChIP correlates with GlcN1 tri-acylation of Lipid A. In an in vivo peritonitis mouse model ChIP displays excellent activity against both colistin sensitive and resistant Escherichia coli and Acinetobacter baumannii strains.


Author(s):  
Ying Zhang ◽  
Yishuai Lin ◽  
Xiaodong Zhang ◽  
Liqiong Chen ◽  
Chunyan Xu ◽  
...  

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.


Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1165
Author(s):  
Rita Elias ◽  
Aida Duarte ◽  
João Perdigão

Klebsiella pneumoniae is a rod-shaped, encapsulated, Gram-negative bacteria associated with multiple nosocomial infections. Multidrug-resistant (MDR) K. pneumoniae strains have been increasing and the therapeutic options are increasingly limited. Colistin is a long-used, polycationic, heptapeptide that has regained attention due to its activity against Gram-negative bacteria, including the MDR K. pneumoniae strains. However, this antibiotic has a complex mode of action that is still under research along with numerous side-effects. The acquisition of colistin resistance is mainly associated with alteration of lipid A net charge through the addition of cationic groups synthesized by the gene products of a multi-genic regulatory network. Besides mutations in these chromosomal genes, colistin resistance can also be achieved through the acquisition of plasmid-encoded genes. Nevertheless, the diversity of molecular markers for colistin resistance along with some adverse colistin properties compromises the reliability of colistin-resistance monitorization methods. The present review is focused on the colistin action and molecular resistance mechanisms, along with specific limitations on drug susceptibility testing for K. pneumoniae.


mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Axel B. Janssen ◽  
Toby L. Bartholomew ◽  
Natalia P. Marciszewska ◽  
Marc J. M. Bonten ◽  
Rob J. L. Willems ◽  
...  

ABSTRACT Infections by multidrug-resistant Gram-negative bacteria are increasingly common, prompting the renewed interest in the use of colistin. Colistin specifically targets Gram-negative bacteria by interacting with the anionic lipid A moieties of lipopolysaccharides, leading to membrane destabilization and cell death. Here, we aimed to uncover the mechanisms of colistin resistance in nine colistin-resistant Escherichia coli strains and one Escherichia albertii strain. These were the only colistin-resistant strains of 1,140 bloodstream Escherichia isolates collected in a tertiary hospital over a 10-year period (2006 to 2015). Core-genome phylogenetic analysis showed that each patient was colonized by a unique strain, suggesting that colistin resistance was acquired independently in each strain. All colistin-resistant strains had lipid A that was modified with phosphoethanolamine. In addition, two E. coli strains had hepta-acylated lipid A species, containing an additional palmitate compared to the canonical hexa-acylated E. coli lipid A. One E. coli strain carried the mobile colistin resistance (mcr) gene mcr-1.1 on an IncX4-type plasmid. Through construction of chromosomal transgene integration mutants, we experimentally determined that mutations in basRS, encoding a two-component signal transduction system, contributed to colistin resistance in four strains. We confirmed these observations by reversing the mutations in basRS to the sequences found in reference strains, resulting in loss of colistin resistance. While the mcr genes have become a widely studied mechanism of colistin resistance in E. coli, sequence variation in basRS is another, potentially more prevalent but relatively underexplored, cause of colistin resistance in this important nosocomial pathogen. IMPORTANCE Multidrug resistance among Gram-negative bacteria has led to the use of colistin as a last-resort drug. The cationic colistin kills Gram-negative bacteria through electrostatic interaction with the anionic lipid A moiety of lipopolysaccharides. Due to increased use in clinical and agricultural settings, colistin resistance has recently started to emerge. In this study, we used a combination of whole-genome sequence analysis and experimental validation to characterize the mechanisms through which Escherichia coli strains from bloodstream infections can develop colistin resistance. We found no evidence of direct transfer of colistin-resistant isolates between patients. The lipid A of all isolates was modified by the addition of phosphoethanolamine. In four isolates, colistin resistance was experimentally verified to be caused by mutations in the basRS genes, encoding a two-component regulatory system. Our data show that chromosomal mutations are an important cause of colistin resistance among clinical E. coli isolates.


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