Emergence of #mcr-8.2-bearing #Klebsiella quasipneumoniae of #animal origin (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Emergence of mcr-8.2-bearing Klebsiella quasipneumoniae of animal origin

Xiaorong Yang, Li Liu, Zhiqiang Wang, Li Bai, Ruichao Li

Journal of Antimicrobial Chemotherapy, dkz213, https://doi.org/10.1093/jac/dkz213

Published: 16 May 2019



The emergence of plasmid-mediated mcr-1, conferring resistance to colistin, which is considered as a last-resort drug to treat carbapenem-resistant Enterobacteriaceae (CRE) infections, poses a severe public health concern.1 Eight different mcr genes mainly mediated by plasmids were identified within 3 years after the reporting of mcr-1 in late 2015.1,2,Klebsiella pneumoniae is a well-known bacterium causing life-threatening infections, especially in neonates, the elderly and immunocompromised individuals.3 The mcr-1, mcr-3, mcr-7 and mcr-8 genes have been detected in K. pneumoniae recently.2,4,Klebsiella quasipneumoniae, which is found in animals and…



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Keywords: Antibiotics; Drugs Resistance; Colistin; Klebsiella pneumoniae; MCR8.



Functional characterization of a Miniature Inverted Transposable Element at the origin of #mcr-5 gene acquisition in #Escherichia coli (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Functional characterization of a Miniature Inverted Transposable Element at the origin of mcr-5 gene acquisition in Escherichia coli

Nicolas Kieffer, Patrice Nordmann, Yves Millemann, Laurent Poirel

DOI: 10.1128/AAC.00559-19



Plasmid-mediated colistin resistance of the MCR type is a growing concern in Enterobacteriaceae since it has been described worldwide either in humans and in animals. Here we identified a series of MCR-producing Escherichia coli isolates, corresponding to two different clones (respectively represented by isolates PS1 and PS8b) producing MCR-1 and MCR-5, respectively, from pig fecal samples in France. Plasmid analysis showed that the plasmid carrying the mcr-1 gene (pPS1) possesses an IncHI2 backbone whereas the mcr-5gene was carried onto a 6,268 bp non-typeable, non self-conjugative plasmid (pPS8b). Detailed analysis of plasmid pPS8b revealed a 3,803 bp-long cassette containing the mcr-5 gene that was bracketed by two inverted-repeat sequences (IRs) with 5-bp long direct repeats at each extremity, similarly to an insertion sequence, but with the exception that no transposase gene was identified within this cassette. By performing in-vitro transposition experiments, we showed that the mcr-5 cassette could be mobilized by the TnAs1 transposase provided in-trans, displaying a similar mobilization mechanism as miniature inverted repeat transposable elements (MITEs).

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Colistin; E. Coli; MCR5; Plasmids.


Identification of Novel Mobilized #Colistin #Resistance #Gene #mcr9 in a #MDR, Colistin-Susceptible #Salmonella enterica Serotype #Typhimurium Isolate (mBio, abstract)

[Source: mBio, full page: (LINK). Abstract, edited.]

Identification of Novel Mobilized Colistin Resistance Gene mcr-9 in a Multidrug-Resistant, Colistin-Susceptible Salmonella enterica Serotype Typhimurium Isolate

Laura M. Carroll, Ahmed Gaballa, Claudia Guldimann, Genevieve Sullivan, Lory O. Henderson, Martin Wiedmann

Mark S. Turner, Editor

DOI: 10.1128/mBio.00853-19



Mobilized colistin resistance (mcr) genes are plasmid-borne genes that confer resistance to colistin, an antibiotic used to treat severe bacterial infections. To date, eight known mcrhomologues have been described (mcr-1 to -8). Here, we describe mcr-9, a novel mcrhomologue detected during routine in silico screening of sequenced Salmonella genomes for antimicrobial resistance genes. The amino acid sequence of mcr-9, detected in a multidrug-resistant (MDR) Salmonella enterica serotype Typhimurium (S. Typhimurium) strain isolated from a human patient in Washington State in 2010, most closely resembled mcr-3, aligning with 64.5% amino acid identity and 99.5% coverage using Translated Nucleotide BLAST (tblastn). The S. Typhimurium strain was tested for phenotypic resistance to colistin and was found to be sensitive at the 2-mg/liter European Committee on Antimicrobial Susceptibility Testing breakpoint under the tested conditions. mcr-9 was cloned in colistin-susceptible Escherichia coliNEB5α under an IPTG (isopropyl-β-d-thiogalactopyranoside)-induced promoter to determine whether it was capable of conferring resistance to colistin when expressed in a heterologous host. Expression of mcr-9 conferred resistance to colistin in E. coli NEB5α at 1, 2, and 2.5 mg/liter colistin, albeit at a lower level than mcr-3. Pairwise comparisons of the predicted protein structures associated with all nine mcr homologues (Mcr-1 to -9) revealed that Mcr-9, Mcr-3, Mcr-4, and Mcr-7 share a high degree of similarity at the structural level. Our results indicate that mcr-9 is capable of conferring phenotypic resistance to colistin in Enterobacteriaceae and should be immediately considered when monitoring plasmid-mediated colistin resistance.



Colistin is a last-resort antibiotic that is used to treat severe infections caused by MDR and extensively drug-resistant (XDR) bacteria. The World Health Organization (WHO) has designated colistin as a “highest priority critically important antimicrobial for human medicine” (WHO, Critically Important Antimicrobials for Human Medicine, 5th revision, 2017, https://www.who.int/foodsafety/publications/antimicrobials-fifth/en/), as it is often one of the only therapies available for treating serious bacterial infections in critically ill patients. Plasmid-borne mcr genes that confer resistance to colistin pose a threat to public health at an international scale, as they can be transmitted via horizontal gene transfer and have the potential to spread globally. Therefore, the establishment of a complete reference of mcr genes that can be used to screen for plasmid-mediated colistin resistance is essential for developing effective control strategies.

Keywords: Antibiotics; Drugs Resistance; Enterobacteriaceae; Salmonella enterica; MCR9; MCR3; Colistin; USA; Plasmids.


Detection of #colistin #resistance #mcr-1 gene in #Salmonella enterica serovar Rissen isolated from #mussels, #Spain, 2012­ to 2016 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Detection of colistin resistance mcr-1 gene in Salmonella enterica serovar Rissen isolated from mussels, Spain, 2012­ to 2016

Antonio Lozano-Leon1,2, Carlos Garcia-Omil1, Jacobo Dalama1, Rafael Rodriguez-Souto1, Jaime Martinez-Urtaza3, Narjol Gonzalez-Escalona4

Affiliations: 1 ASMECRUZ Laboratory. Playa de Beluso s/n 36939, Pontevedra, Spain; 2 CI8 Research Group. Department Chemistry and Food Analysis, University of Vigo, As Lagoas-Marcosende 36310 Vigo, Pontevedra, Spain; 3 Centre for Environment, Fisheries and Aquaculture Science (Cefas), Barrack Road, Weymouth, Dorset, United Kingdom; 4 Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, Maryland, United States

Correspondence:  Antonio Lozano-Leon

Citation style for this article: Lozano-Leon Antonio, Garcia-Omil Carlos, Dalama Jacobo, Rodriguez-Souto Rafael, Martinez-Urtaza Jaime, Gonzalez-Escalona Narjol. Detection of colistin resistance mcr-1 gene in Salmonella enterica serovar Rissen isolated from mussels, Spain, 2012­ to 2016. Euro Surveill. 2019;24(16):pii=1900200. https://doi.org/10.2807/1560-7917.ES.2019.24.16.1900200

Received: 20 Mar 2019;   Accepted: 16 Apr 2019



Nineteen Salmonella strains were isolated from 5,907 randomly selected mussel samples during a monitoring programme for the presence of Salmonella in shellfish in Galicia, north-west Spain (2012–16). Serovars, sequence type and antimicrobial resistance genes were determined through genome sequencing. Presence of the mcr-1 gene in one strain belonging to serovar Rissen and ST-469 was identified. The mcr-1 gene had not been isolated previously in environmental Salmonella isolated from mussels in Spain.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Antibiotics; Drugs Resistance; Colistin; MCR1; Salmonella enterica; Spain.


#Synergistic effect of #colistin combined with PFK-158 against colistin-resistant #Enterobacteriaceae (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Synergistic effect of colistin combined with PFK-158 against colistin-resistant Enterobacteriaceae

Youwen Zhang, Xiukun Wang, Xue Li, Limin Dong, Xinxin Hu, Tongying Nie, Yun Lu, Xi Lu, Jing Pang, Guoqing Li, Xinyi Yang, Congran Li, Xuefu You

DOI: 10.1128/AAC.00271-19



As increasing numbers of colistin-resistant bacteria emerge, new therapies are urgently needed to treat infections caused by these pathogens. The discovery of new combination therapies is one important way to solve such problems. Herein, we report that the antitumor drug PFK-158 and its analogs PFK-015 and 3PO can exert synergistic effects with colistin against colistin-resistant Enterobacteriaceae, including mcr-1 positive or high-level colistin resistant (HLCR) isolates, as shown by a checkerboard assay. The results of a time-killing assay revealed that colistin combined with PFK-158 continuously eliminated colistin-resistant Escherichia coli 13-43, Klebsiella pneumoniae H04 and Enterobacter cloacae D01 in 24 h. Images from scanning electron microscopy (SEM) 5 h post-inoculation confirmed the killing effect of the combination. Finally, the in vivo treatment showed that PFK-158 had a better synergistic effect than its analogs. Compared to the corresponding rates after colistin monotherapy, the survival rates of systemically infected mice were significantly increased 30% or 60% when the mice received an intravenous injection of colistin in combination with 15 mg/kg PFK-158. These results have important implications for repurposing PFK-158 to combat colistin resistance.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Enterobacteriaceae; MCR1; Colistin.


The #application of #CRISPR/Cas9-based genome editing in studying the #mechanism of #pandrug #resistance in #Klebsiella pneumoniae (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

The application of CRISPR/Cas9-based genome editing in studying the mechanism of pandrug resistance in Klebsiella pneumoniae

Qiaoling Sun, Yu Wang, Ning Dong, Lingwei Shen, Hongwei Zhou, Yan-yan Hu, Danxia Gu, Sheng Chen, Rong Zhang, Quanjiang Ji

DOI: 10.1128/AAC.00113-19



In this study, a CRISPR/Cas9-mediated genome editing method was used to study the functions of genes mgrB, tetA and ramR in mediating colistin and tigecycline resistance in carbapenem-resistant Klebsiella pneumoniae. Inactivation of the tetA, ramR, or mgrB genes by CRISPR/Cas9 affected bacterial susceptibility to tigecycline or colistin, respectively. This study proved that the CRISPR/Cas9-based genome editing method could be effectively applied to K. pneumoniae and should be further utilized for genetic characterization.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Colistin; Tigecycline; CRISPR.


Most #domestic #livestock possess #colistin-resistant commensal #Escherichia coli harboring #mcr in a rural community in #Vietnam (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Most domestic livestock possess colistin-resistant commensal Escherichia coli harboring mcr in a rural community in Vietnam

Ryuji Kawahara, Yoshihiro Fujiya, Takahiro Yamaguchi, Diep Thi Khong, Thang Nam Nguyen, Hoa Thi Tran, Yoshimasa Yamamoto

DOI: 10.1128/AAC.00594-19



Colistin is recognized as the last resort for treatment of life-threatening infections caused by multidrug-resistant bacteria; however, the increasing prevalence of colistin-resistant bacteria harboring the mobile colistin resistance gene (mcr) poses a threat to the treatment (1).…

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Colistin; E. Coli; Livestock; Vietnam; MCR1.