Plasmid-borne Colistin Resistance Gene Research Articles

Outer membrane permeability of mcr-positive bacteria reveals potent synergy of colistin and macromolecular antibiotics against colistin-resistant Acinetobacter baumannii.

Colistin (CT) is the last-resort of antibiotic against multidrug-resistance (MDR) Acinetobacter baumannii (A. baumannii) infection. However, colistin resistance is increasingly reported in A. baumannii isolates partially due to the global emergence and dissemination of plasmid-borne mobile colistin resistance (mcr) gene and is a threat to human health. Thus, available treatment strategies urgently required in the fight against colistin-resistant A. baumannii. Here, we showed that mcr confers damaged outer membrane (OM) permeability in A. baumannii, which could compromise the viability of A. baumannii. Consistently, A. baumannii with colistin resistance exhibits increased susceptibility to macromolecular antibiotics such as rifampicin (RIF) and erythromycin (ERY). Moreover, the combination therapy of colistin and rifampicin demonstrates efficacy against colistin-resistant A. baumannii, regardless of the presence of mcr. Altogether, our data suggest that the synergy of colistin in combination with macromolecular hydrophobic antibiotics poses a promising therapeutic alternative for colistin-resistant A. baumannii.

VIM-1-producing Enterobacter asburiae with mobile colistin resistance genes from wastewaters

BackgroundWastewaters are considered as important players in the spread of antimicrobial resistance, thus affecting the health of humans and animals. Here, we focused on wastewaters as a possible source of carbapenemase-producing Enterobacterales for the environment.MethodsA total of 180 presumptive coliforms from hospital and municipal wastewaters, and a river in the Czech Republic were obtained by selective cultivation on meropenem-supplemented media and tested for presence of carbapenemase-encoding genes by PCR. Strains carrying genes of interest were characterized by testing antimicrobial susceptibility, carbapenemase production and combination of short- and long- read whole-genome sequencing. The phylogenetic tree including publicly available genomes of Enterobacter asburiae was conducted using Prokka, Roary and RAxML.ResultsThree VIM-producing Enterobacter asburiae isolates, members of the Enterobacter cloacae complex, were detected from hospital and municipal wastewaters, and the river. The blaVIM−1 gene was located within a class 1 integron that was carried by different F-type plasmids and one non-typeable plasmid. Furthermore, one of the isolates carried plasmid-borne colistin-resistance gene mcr-10, while in another isolate chromosomally located mcr-9 without colistin resistance phenotype was detected. In addition, the analysis of 685 publicly available E. asburiae genomes showed they frequently carry carbapenemase genes, highlighting the importance of this species in the emergence of resistance to last-line antibiotics.ConclusionOur findings pointed out the important contribution of hospital and community wastewaters in transmission of multi-drug resistant pathogens.

Emergence of the mobile colistin resistance gene mcr-1 in a Leclercia adecarboxylata strain isolated from wastewater in Seoul

Colistin is considered the last resort for treating infections caused by multidrug-resistant bacteria. However, the spread of the plasmid-borne colistin-resistance gene mcr-1 has become a public health threat. In this study, we identified mcr-1-harboring Leclercia adecarboxylata strain (WWCOL-134) isolated from wastewater in Seoul. The strain had a colistin MIC value of 2 µg/ml and was resistant to cefotaxime, gentamicin, tetracycline, trimethoprim and sulfamethoxazole. The mcr-1 gene, along with an array of resistance genes, was located on a 236-kb plasmid (pCOL134-1), which contained the typical IncHI2 backbone of reported mcr-1-carrying plasmids, and was transferred to an Escherichia coli strain by conjugation. To the best of our knowledge, this is the first study to report the emergence of mcr-1-harboring Leclercia sp. isolate. Our findings demonstrate the ongoing spread of colistin resistance among Enterobacterales species, emphasizing the need for surveillance of antimicrobial resistance in wastewater environments.

Complete Genome Sequence of an mcr-10-Carrying Enterobacter roggenkampii Strain Isolated from a Human Blood Culture.

The mcr-10 gene is a plasmid-borne colistin resistance gene. The complete genome sequence of an mcr-10-carrying Enterobacter roggenkampii clinical strain that had been isolated from a blood culture was obtained. The genome consists of a 4.95-Mbp chromosome and six plasmids, including a 195-kb plasmid harboring mcr-10 and two replicons, IncFIB(K) and IncFII(Yp).

Emergence of a novel hybrid mcr-1-bearing plasmid in an NDM-7-producing ST167 Escherichia coli strain of clinical origin.

Colistin is considered as an antibiotic of ‘last resort’ for the treatment of lethal infections caused by carbapenem-resistant Enterobacterales (CRE), dissemination of plasmid-borne colistin resistance gene mcr-1, particularly into CRE, resulting in the emergence of strains that approach pan-resistance. A wide variety of plasmid types have been reported for carrying mcr-1. Among which, large IncHI2-type plasmids were multidrug-resistant (MDR) plasmids harbored multiple resistance determinants in addition to mcr-1. Herein, we characterized a novel hybrid IncHI2-like mcr-1-bearing plasmid in an NDM-7-producing ST167 Escherichia coli strain EC15-50 of clinical origin. Antimicrobial susceptibility testing showed E. coli EC15-50 exhibited an extensively drug-resistant (XDR) profile that only susceptible to amikacin and tigecycline. S1-PFGE, Southern hybridization and Whole-genome Sequencing (WGS) analysis identified a 46,161 bp blaNDM-7-harboring IncX3 plasmid pEC50-NDM7 and a 350,179 bp mcr-1-bearing IncHI2/HI2A/N/FII/FIA plasmid pEC15-MCR-50 in E. coli EC15-50. Sequence detail analysis revealed the type IV coupling protein (T4CP) gene was absent on pEC15-MCR-50, explaining that pEC15-MCR-50 was a non-conjugative plasmid. Comparative genetic analysis indicated the hybrid plasmid pEC15-MCR-50 was probably originated from pXGE1mcr-like IncHI2/HI2A/N plasmid and pSJ_94-like IncFII/FIA plasmid, and generated as a result of a replicative transposition process mediated by IS26. Currently, the prevalent mcr-1-carrying IncHI2 plasmids were rarely reported to be fused with other plasmids. The identification of the novel hybrid plasmid pEC15-MCR-50 in this study highlighted the importance of close surveillance for the emergence and dissemination of such fusion MDR plasmids, particularly in NDM-producing Enterobacterales.

Letter to the Editor: First Report of the Detection of the Plasmid-Borne Colistin Resistance Gene, mcr-1.26, in Multidrug-Resistant Escherichia coli Isolated from a Domesticated Pigeon.

Microbial Drug ResistanceVol. 28, No. 7 Veterinary MicrobiologyLetter to the Editor: First Report of the Detection of the Plasmid-Borne Colistin Resistance Gene, mcr-1.26, in Multidrug-Resistant Escherichia coli Isolated from a Domesticated PigeonIssmat I. Kassem, Ali Assi, Marwan Osman, David Mann, Shaoting Li, and Xiangyu DengIssmat I. KassemAddress correspondence to: Issmat I. Kassem, PhD, Food Science and Technology, Center for Food Safety, University of Georgia, 1109 Experiment Street, Griffin, GA 30223, USA E-mail Address: issmat.kassem@uga.eduFood Science and Technology, Center for Food Safety, University of Georgia, Athens, Georgia, USA.Search for more papers by this author, Ali AssiNutrition and Food Sciences, Faculty of Agricultural and Food Sciences, American University of Beirut (AUB), Beirut, Lebanon.Search for more papers by this author, Marwan OsmanDepartment of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.Search for more papers by this author, David MannFood Science and Technology, Center for Food Safety, University of Georgia, Athens, Georgia, USA.Search for more papers by this author, Shaoting LiFood Science and Technology, Center for Food Safety, University of Georgia, Athens, Georgia, USA.Search for more papers by this author, and Xiangyu DengFood Science and Technology, Center for Food Safety, University of Georgia, Athens, Georgia, USA.Search for more papers by this authorPublished Online:13 Jul 2022https://doi.org/10.1089/mdr.2021.0359AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited byEditorial: Antimicrobial resistance and antimicrobial alternatives6 March 2023 | Frontiers in Medicine, Vol. 10 Volume 28Issue 7Jul 2022 InformationCopyright 2022, Mary Ann Liebert, Inc., publishersTo cite this article:Issmat I. Kassem, Ali Assi, Marwan Osman, David Mann, Shaoting Li, and Xiangyu Deng.Letter to the Editor: First Report of the Detection of the Plasmid-Borne Colistin Resistance Gene, mcr-1.26, in Multidrug-Resistant Escherichia coli Isolated from a Domesticated Pigeon.Microbial Drug Resistance.Jul 2022.821-823.http://doi.org/10.1089/mdr.2021.0359Published in Volume: 28 Issue 7: July 13, 2022Online Ahead of Print:May 30, 2022PDF download

Prevalence and Antibiotic Resistance Characteristics of Extraintestinal Pathogenic Escherichia coli among Healthy Chickens from Farms and Live Poultry Markets in China.

Simple SummaryChicken meat has been proved to be a suspected source of extraintestinal pathogenic Escherichia coli (ExPEC), causing several diseases in humans, and bacteria in healthy chickens can contaminate chicken carcasses at the slaughter; however, reports about the prevalence and molecular characteristics of ExPEC in healthy chickens are still rare. In this study, among 926 E. coli isolates from healthy chickens in China, 22 (2.4%) were qualified as ExPEC and these ExPEC isolates were clonally unrelated. A total of six serogroups were identified in this study, with O78 being the most predominant type, and all the six serogroups had been frequently reported in human ExPEC isolates in many countries. All the 22 ExPEC isolates were multidrug-resistant and most isolates carried both blaCTX-M and fosA3 resistance genes. Notably, plasmid-borne colistin resistance gene mcr-1 was identified in six ExPEC isolates, among which two carried additional carbapenemase gene blaNDM, compromising both the efficacies of the two critically important drugs for humans, carbapenems and colistin. These results highlight that healthy chickens can serve as a potential reservoir for multidrug resistant ExPEC isolates, including mcr-1-containing ExPEC.Chicken products and chickens with colibacillosis are often reported to be a suspected source of extraintestinal pathogenic Escherichia coli (ExPEC) causing several diseases in humans. Such pathogens in healthy chickens can also contaminate chicken carcasses at the slaughter and then are transmitted to humans via food supply; however, reports about the ExPEC in healthy chickens are still rare. In this study, we determined the prevalence and characteristics of ExPEC isolates in healthy chickens in China. A total of 926 E. coli isolates from seven layer farms (371 isolates), one white-feather broiler farm (78 isolates) and 17 live poultry markets (477 isolates from yellow-feather broilers) in 10 cities in China, were isolated and analyzed for antibiotic resistance phenotypes and genotypes. The molecular detection of ExPEC among these healthy chicken E. coli isolates was performed by PCRs, and the serogroups and antibiotic resistance characteristics of ExPEC were also analyzed. Pulsed-field gel electrophoresis (PFGE) and Multilocus sequence typing (MLST) were used to analyze the genetic relatedness of these ExPEC isolates. We found that the resistance rate for each of the 15 antimicrobials tested among E. coli from white-feather broilers was significantly higher than that from brown-egg layers and that from yellow-feather broilers in live poultry markets (p < 0.05). A total of 22 of the 926 E. coli isolates (2.4%) from healthy chickens were qualified as ExPEC, and the detection rate (7.7%, 6/78) of ExPEC among white-feather broilers was significantly higher than that (1.6%, 6/371) from brown-egg layers and that (2.1%, 10/477) from yellow-feather broilers (p < 0.05). PFGE and MLST analysis indicated that clonal dissemination of these ExPEC isolates was unlikely. Serogroup O78 was the most predominant type among the six serogroups identified in this study, and all the six serogroups had been frequently reported in human ExPEC isolates in many countries. All the 22 ExPEC isolates were multidrug-resistant (MDR) and the resistance rates to ampicillin (100%) and sulfamethoxazole-trimethoprim (100%) were the highest, followed by tetracycline (95.5%) and doxycycline (90.9%). blaCTX-M was found in 15 of the 22 ExPEC isolates including 10 harboring additional fosfomycin resistance gene fosA3. Notably, plasmid-borne colistin resistance gene mcr-1 was identified in six ExPEC isolates in this study. Worryingly, two ExPEC isolates were found to carry both mcr-1 and blaNDM, compromising both the efficacies of carbapenems and colistin. The presence of ExPEC isolates in healthy chickens, especially those carrying mcr-1 and/or blaNDM, is alarming and will pose a threat to the health of consumers. To our knowledge, this is the first report of mcr-1-positive ExPEC isolates harboring blaNDM from healthy chickens.

Potential Mobilization of mcr-10 by an Integrative Mobile Element via Site-Specific Recombination in Cronobacter sakazakii.

mcr-10 is a newly identified plasmid-borne colistin resistance gene, but its mobilization mechanism remains unclear. In this study, mcr-10 was found on an IncFIB plasmid carrying virulence genes mrkABCDFJ, iucABCD/iutA, and eitCBAD in a Cronobacter sakazakii isolate. By comparison with closely related plasmids, two recombination sites were identified flanking the genetic element containing mcr-10 and an integrase-encoding gene, suggesting that site-specific recombination mediated by an integrase of an integrative mobile element is a potential mechanism for mobilizing mcr-10.

Draft Genome Sequences of Multidrug-Resistant and mcr-1.1-Harboring Escherichia coli Isolated from Drinking and Well Waters Used in Syrian Refugee Camps.

Resistance to colistin, a last-resort antibiotic, threatens the treatment of complicated infections, especially in susceptible populations such as Syrian refugees who live in makeshift camps. Two multidrug-resistant Escherichia coli strains with the plasmid-borne colistin resistance gene (mcr-1.1) were isolated from the waters used by refugees and sequenced to analyze antibiotic resistance determinants.

First Report of Colistin Resistance Gene mcr-1 in Carbapenem-Resistant Clinical Isolates of Klebsiella Pneumoniae in Iraq

Background: The prevalence of the plasmid-borne colistin resistance gene mcr-1 in bacteria poses a potentialthreat to patient treatment, particularly when hospitalized spreading of this gene causes great concern as itcan transmit between different bacteria species. The aims of this study were to investigate the presence ofthe mcr-1 gene among carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from different clinicalspecimens and determine the clonal origin of strains carrying the mcr-1 gene using Multi-locus sequencetyping (MLST) method.Method: In this study, 22 CRKP isolates from clinical specimens collected from the major four hospitals inNajaf/Iraq were examined. All isolates were identified by a standard biochemical test and confirmed by anautomated Vitek®2 system. Antimicrobial susceptibility test was done on 12 antibiotics by the disk diffusionmethod. All isolates tested to detect the presence of the mcr-1 gene using the PCR method. Determine thesequence typing by MLST for all mcr-1-positive CRKP isolates.Results: Out of 147 K.pneumoniae, 22 carbapenem resistance isolates from different clinical specimenswere detected. Antibiotic sensitivity test results revealed that all isolates (100 %) were resistant to ampicillin,Cefepime, Cefoxitin, Ceftazidime, and Ceftriaxone; however, most of the CRKP isolates (86.4 %) aresensitive to colistin. The mcr-1 gene was found in three (13.6%) of the 22 isolates of CRKP.These threeisolates are resistant to all classes of antibiotics. The MLST results revealed that three mcr-1-positive CRKPisolates were related to three different sequence types: ST147, ST1, and ST11.Conclusion: The spread of CRKP isolates containing plasmid-borne mcr-1gene is worth our attention dueto the consider of colistin as the last resort treatment against drug-resistant pathogens that increasinglyidentified in Najaf Hospitals/Iraq.

First report of the mcr-1 colistin resistance gene identified in two Escherichia coli isolates from clinical samples, Philippines, 2018

ObjectivesThe first report of a plasmid-borne colistin resistance gene (mcr-1) detected in an Escherichia coli isolate from China heralded the emergence of pandrug-resistant bacteria. Since then, the mcr-1 gene has been detected worldwide, but to date it has not been reported in the Philippines. MethodsIn this study, 123 antimicrobial-resistant isolates collected from January–June 2018 from patients admitted to a tertiary hospital in Manila, Philippines, were characterised. Biochemical identification and antimicrobial susceptibility testing were performed using a BD Phoenix™ M50 system with NMIC/ID-95 panel. Conventional PCR was performed to detect the genes mcr-1 to mcr-5, and short- and long-read whole-genome sequencing was performed. ResultsTwo mcr-1-positive E. coli clinical isolates from separate patients harboured mcr-1 on an IncI2 plasmid. One isolate was shown to carry 12 antimicrobial resistance genes (ARGs) in addition to mcr-1, including the extended-spectrum β-lactamase blaCTX-M-55, whilst the other E. coli isolate carried 6 ARGs in addition to mcr-1. ConclusionBoth patients had no prior colistin treatment recorded in their medical history and no travel history outside of the country within the past 6 months from the date of hospital admission, indicating local transmission and acquisition of the colistin-resistant strain from either community or hospital settings within the Philippines. This report should serve as a signal to local public-health officials of the need to intensify surveillance efforts and to increase vigilance and implementation of antimicrobial stewardship programmes to contain and slow the spread of antimicrobial resistance.

Identification of novel mobile colistin resistance gene mcr-10

ABSTRACT Mobile colistin resistance (mcr) genes represent an emerging challenge. Here we describe a novel mcr gene, mcr-10, on an IncFIA plasmid of an Enterobacter roggenkampii clinical strain. mcr-10 has the highest nucleotide identity (79.69%) with mcr-9 and encodes MCR-10 with 82.93% amino acids identical to MCR-9. mcr-10 confers 4-fold increase in colistin MIC (from 1 to 4 mg/L) when cloned into a colistin-susceptible E. roggenkampii strain. By screening GenBank, mcr-10 was found in various Enterobacteriaceae species of countries in four continents, suggesting that this gene has widely spread. MCR-10 shows 79.04% to 83.67% amino acid identity and highly conserved predicted protein structures with chromosomally encoded MCR-like phosphoethanolamine transferases (designated MCR-B here) of various Buttiauxella species. MCR-10, MCR-9 and MCR-B proteins may, therefore, originate from a common ancestor. mcr-10 was adjacent to a site-specific recombinase-encoding gene and was bracketed by IS903 and may be mobilized by site-specific recombination or composite transposon. Our results indicate that mcr-10 is a novel plasmid-borne colistin resistance gene and warrants immediate monitoring and further studies.

First report on the detection of the plasmid-borne colistin resistance gene mcr-1 in multi-drug resistant E. coli isolated from domestic and sewer waters in Syrian refugee camps in Lebanon

First report on the detection of the plasmid-borne colistin resistance gene mcr-1 in multi-drug resistant E. coli isolated from domestic and sewer waters in Syrian refugee camps in Lebanon

Co-occurrence of clinically relevant β-lactamases and MCR-1 encoding genes in Escherichia coli from companion animals in Argentina

Extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC (pAmpC) and MCR-1 phosphoethanolamine transferase enzymes have been pointed out as the main plasmid-mediated mechanisms of resistance to third generation cephalosporins (TGC) and colistin, respectively, and are currently considered a major concern both in human and veterinary medicine. Little data on these resistance determinants prevalence in companion animal infections is available. The aim of this study was to determine the resistance profile of Escherichia coli isolated from pet infections, in Argentina, and to characterize the resistance mechanisms to TGC, as well as the presence of the plasmid-borne colistin resistance gene, mcr-1. A total of 54 E. coli isolates were collected from clinical samples in dogs and cats; from them, 20/54 (37%, CI95: [24%; 51%]) displayed resistance to TGC. In this regard, thirteen pAmpC-producing isolates were positive for blaCMY-2 genes, whereas seven ESBL- producers harboured blaCTX-M-2 (n = 4), blaCTX-M-15 (n = 2) and blaCTX-M-14 (n = 1) genes. One E. coli strain (V80), isolated from a canine urinary tract infection, showed resistance to colistin (MIC = 8 μg/ml) and whole-genome sequencing analysis revealed co-occurrence of mcr-1.1, blaCTX-M-2, aadA1, ant(2′')-Ia, catA1 and sul1 genes; the former being carried by a 60,587-bp IncI2 plasmid, previously reported in human colistin-resistant E. coli. E. coli V80 belonged to ST770 and the highly virulent phylogenetic group B2. In general, most of these multidrug-resistant isolates belonged to the phylogenetic group F (11/20) and to a lesser extent B2 (5/20), B1 (2/20), D (1/20) and E (1/20). In summary, CMY- and CTX-M-type β-lactamases may constitute the main TGC resistance mechanism in E. coli isolated from pet infections in Argentina, whereas dissemination of colistin resistance mechanism MCR-1 in the human-animal interface has been mediated by IncI2 plasmids.

Population dynamics models based on the transmission mechanism of MCR-1

Antimicrobial resistance is now considered as one of the most serious global threats to human health in the 21st century. Recently, the discovery of a plasmid-borne colistin resistance gene, mcr-1, in China heralds the emergence of truly pan-drug-resistant bacteria. The gene has been found primarily in Escherichia coli but has also been identified in other members of the Enterobacteriaceae in animal, food, human, and environmental samples on every continent. Until now, the articles published have appeared to fairly use and interpret experimental studies. The aim of our work is to develop mathematic models that quantitatively describe the dynamic of the population of domestic animals and humans. We propose two ordinary differential equation models for the transmission dynamic of mcr-1 gene. The models are analyzed using stability theory of differential equations. Positive equilibrium points of the system are investigated and their stability analyses are carried out. Moreover, the numerical simulations of the proposed model are also represented Our results show that the fraction of animals used for human consumption is the most effective parameters of controlling the spread of mcr-1 gene in comparison with other parameters.

Exploiting a conjugative CRISPR/Cas9 system to eliminate plasmid harbouring the mcr-1 gene from Escherichia coli

The transfer of multi-drug-resistance plasmids by bacterial conjugation is largely responsible for the development of drug resistance in bacteria, and causes serious problems in the treatment of infectious diseases. Since the first discovery of plasmid-borne colistin resistance gene mcr-1 was reported in late 2016, this gene has been found in a great number of Escherichia coli and other Gram-negative pathogens separated from different types of sources worldwide. The elimination of plasmids carrying mcr-1 and restoration of polymyxin sensitivity has very important clinical significance because polymyxins are frequently used as last-resort antibiotics to treat extensively drug-resistant Gram-negative bacterial infections. A host-independent conjugative plasmid was constructed in this study, and an engineered CRISPR/Cas9 system was used to remove plasmid harbouring mcr-1 from bacteria. This study found that this conjugative plasmid can not only be used as a new tool to remove resistance plasmids and sensitize the recipient bacteria to antibiotics, but can also make the recipient cell acquire immunity against mcr-1. This strategy provides a novel method to counteract the ever-worsening spread of mcr-1 among bacterial pathogens.

Prevalence of the colistin resistance gene mcr-1 in colistin-resistant Escherichia coli and Klebsiella pneumoniae isolated from humans in Thailand.

Historically, colistin has been considered a last-line therapeutic option against multidrug-resistant Gram-negative bacterial infections. However, chromosomally-encoded and plasmid-mediated colistin resistance is increasingly being reported worldwide. Spread of the plasmid-borne colistin resistance gene mcr-1 is of great concern since it can be transferred between bacteria. The aim of this study was to investigate the prevalence of mcr-1 in Escherichia coli and Klebsiella pneumoniae collected from human clinical specimens in Thailand during 2014-2017. Minimum inhibitory concentrations (MICs) of colistin were determined by the broth microdilution method for 317 non-duplicate Enterobacteriaceae clinical isolates (37 E. coli and 280 K. pneumoniae). All isolates were screened for the mcr-1 gene by PCR. The colistin MIC50, MIC90 and MIC range for the 37 E. coli isolates were 0.5, 8 and 0.5-32mg/L, respectively. The mcr-1 gene was detected in 11 E. coli isolates (29.7%). Escherichia coli harbouring the mcr-1 gene had a colistin MIC range of 4-32mg/L. The colistin MIC50, MIC90, and MIC range for the 280 K. pneumoniae isolates were 32, >128, and 0.25 to >128mg/L, respectively. The mcr-1 gene was detected in 4 K. pneumoniae isolates (1.4%). Klebsiella pneumoniae harbouring the mcr-1 gene had a colistin MIC range of 4-64mg/L. This is the first report on the prevalence of the mcr-1 gene in colistin-resistant E. coli and K. pneumoniae isolated from humans in Thailand. These data provide added insight into the mechanism of colistin resistance among Enterobacteriaceae pathogens.

Susceptibility of colistin-resistant pathogens to predatory bacteria

The increase in multidrug-resistant Gram-negative bacterial infections has forced the reintroduction of antibiotics such as colistin. However, the spread of the plasmid-borne mcr-1 colistin resistance gene have moved us closer to an era of untreatable Gram-negative infections. To evaluate whether predatory bacteria could be used as a potential therapeutic to treat this upcoming threat, the ability of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus to prey on several clinically relevant mcr-1-positive, colistin-resistant isolates was evaluated. No change in the ability of the predators to prey on free swimming and biofilms of prey cells harboring mcr-1 was measured, as compared to their mcr-1 negative strain.

Plasmid-borne colistin resistance gene mcr-3 in Salmonella isolates from human infections, Denmark, 2009-17.

This report describes one Salmonella isolate harbouring both mcr-1 and mcr-3. We also found nine other Salmonella isolates positive for the plasmid-borne colistin resistance gene, mcr-3. The strains were isolated from patients in Denmark between 2009 and 2017 and five of the patients had travelled to Asia. In addition to mcr-3, all strains were found positive for blaTEM-1, strA, strB, sul2 and tet(A) or tet(B), and most strains were positive for blaCTX-M-55 and qnrS.

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

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.