Colistin Resistance Gene mcr-8 in a High-Risk Sequence Type 15 Klebsiella pneumoniae Isolate from Kenya.
Ontology highlight
ABSTRACT:
SUBMITTER: Kyany'a C
PROVIDER: S-EPMC7516148 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
Colistin Resistance Gene <i>mcr-8</i> in a High-Risk Sequence Type 15 Klebsiella pneumoniae Isolate from Kenya.
Kyany'a Cecilia C Musila Lillian L
Microbiology resource announcements 20200924 39
The emergence and rise of mobile colistin resistance genes are of great global concern due to the ease of transfer of resistance to other bacteria. This report describes the genome of a colistin- and multidrug-resistant <i>Klebsiella pneumoniae</i> isolate bearing <i>mcr-8</i>, obtained from a hospitalized patient in Kenya. ...[more]
Similar Datasets
Project description:The emergence of mobilized colistin resistance genes (mcr) has become a serious concern in clinical practice, compromising treatment options for life-threatening infections. In this study, colistin-resistant Klebsiella pneumoniae harboring mcr-8.1 was recovered from infected patients in the largest public hospital of Bangladesh, with a prevalence of 0.3% (3/1,097). We found mcr-8.1 in an identical highly stable multidrug-resistant IncFIB(pQil) plasmid of ?113?kb, which belonged to an epidemiologically successful K. pneumoniae clone, ST15. The resistance mechanism was proven to be horizontally transferable, which incurred a fitness cost to the host. The core genome phylogeny suggested the clonal spread of mcr-8.1 in a Bangladeshi hospital. Core genome single-nucleotide polymorphisms among the mcr-8.1-positive K. pneumoniae isolates ranged from 23 to 110. It has been hypothesized that mcr-8.1 was inserted into IncFIB(pQil) with preexisting resistance loci, bla TEM-1b and bla CTX-M-15, by IS903B Coincidentally, all resistance determinants in the plasmid [mcr-8.1, ampC, sul2, 1d-APH(6), APH(3'')-Ib, bla TEM-1b, bla CTX-M-15] were bracketed by IS903B, demonstrating the possibility of intra- and interspecies and intra- and intergenus transposition of entire resistance loci. This is the first report of an mcr-like mechanism from human infections in Bangladesh. However, given the acquisition of mcr-8.1 by a sable conjugative plasmid in a successful high-risk clone of K. pneumoniae ST15, there is a serious risk of dissemination of mcr-8.1 in Bangladesh from 2017 onwards.IMPORTANCE There is a marked paucity in our understanding of the epidemiology of colistin-resistant bacterial pathogens in South Asia. A report by Davies and Walsh (Lancet Infect Dis 18:256-257, https://doi.org/10.1016/S1473-3099(18)30072-0, 2018) suggests the export of colistin from China to India, Vietnam, and South Korea in 2016 was approximately 1,000 tons and mainly used as a poultry feed additive. A few reports forecast that the prevalence of mcr in humans and livestock will increase in South Asia. Given the high prevalence of bla CTX-M-15 and bla NDM in India, Bangladesh, and Pakistan, colistin has become the invariable option for the management of serious infections, leading to the emergence of mcr-like mechanisms in South Asia. Systematic scrutiny of the prevalence and transmission of mcr variants in South Asia is vital to understanding the drivers of mcr genes and to initiate interventions to overcome colistin resistance.
| S-EPMC7067589 | biostudies-literature
Project description:We report intestinal carriage of an extended-spectrum β-lactamase-producing Klebsiella pneumoniae strain with high-level resistance to colistin (MIC 24 mg/L) in a patient in France who had been hospitalized for fungal meningitis. The strain had the mcr-1 plasmid gene and an inactivated mgrB gene, which are associated with colistin resistance.
| S-EPMC5403025 | biostudies-literature
Project description:Colistin is considered as a last resort treatment for infections caused by multidrug-resistant Enterobacteriaceae. Plasmid-mediated mobile colistin resistance (mcr) genes contributed to the global spread of colistin resistance. This is the first report of plasmid-mediated colistin resistance mcr-8 gene from a clinical Klebsiella pneumoniae K9 isolate recovered from Lebanon. The isolate was characterized phenotypically and genotypically through both short and long read whole-genome sequencing, plasmid typing and conjugation assays. k9 belonged to sequence type 15 and harbored 31 antimicrobial resistance genes. The mcr-8.1 variant was carried on a novel ~ 300 kb multireplicon plasmid having IncFIA, IncR and IncHI1B. The plasmid was conjugative and carried a plethora of antimicrobial resistance determinants. The introduction of novel mcr variants in Lebanon poses an alarming health concern. Surveillance and screening for colistin resistant Enterobacteriaceae and mcr in livestock, animal farms, imported meat and poultry is highly recommended along with monitoring antibiotic use.
| S-EPMC7318401 | biostudies-literature
Project description:Klebsiella pneumoniae is a nosocomial pathogen with high morbidity and mortality rates in hospitalized patients. The emergence of multidrug-resistant K. pneumoniae has become more challenging to treat, with the prevalence of colistin-resistance. Therefore, reliable methods for detecting colistin resistance are required. Many plants' essential oils have antimicrobial activity and have been used to combat multiple antibiotic resistances. This study aimed to investigate the characterization and prevalence of the colistin resistance gene mcr-1 in K. pneumoniae in Egypt, evaluate rapid polymyxin NP test, determine the transferability of mcr-1 gene, and study the synergistic activity of eugenol combined with colistin against K. pneumoniae isolates. Eighty-two K. pneumonia isolates were collected from different human samples, followed by antibiotic susceptibility testing, rapid polymyxin NP test, and detection of the mcr-1 gene and its transfer frequency. Determination of the MICs of colistin alone and in combination with eugenol was performed, then mcr-1 gene expression was determined in the presence of eugenol. Thirty-two isolates (39%) were colistin-resistant. Rapid polymyxin NP test failed to detect resistant isolates with MICs below 32 µg/mL. Detection of mcr-1 gene was made in 27 (84%) of colistin resistant isolates. The rest isolates possess alteration in the mgrB gene which probably causes colistin resistance. The mcr-1 gene was transferred by conjugation to other sensitive isolates. MIC of eugenol ranged from 416 to 1664 µg/mL, and FICI ranged from 0.265 to 0.75. Results also revealed suppression of mcr-1 gene expression in the presence of sub MIC of eugenol. Our results demonstrated a high prevalence of mcr-1 in Egypt and its ability to transfer to other strains. Difficult determination of colistin-resistant isolates with low values with rapid polymyxin NP test was apparent. Eugenol exerted a synergistic effect with colistin and improved its antimicrobial activity.
| S-EPMC10113170 | biostudies-literature
Project description:A Klebsiella pneumoniae strain of sequence type 313 (ST313) recovered from hospital sewage was found carrying the plasmid-borne colistin resistance gene mcr-1, which was bracketed by two copies of the insertion sequence ISApl1 on a 57-kb self-transmissible IncP-type plasmid of a new IncP-1 clade. The carriage of mcr-1 on a self-transmissible broad-host-range plasmid highlights that mcr-1 has the potential to spread beyond the Enterobacteriaceae family.
| S-EPMC5278755 | biostudies-literature
Project description:The rapid increase in carbapenem resistance among gram-negative bacteria has renewed focus on the importance of polymyxin antibiotics (colistin or polymyxin E). However, the recent emergence of plasmid-mediated colistin resistance determinants (mcr-1, -2, -3, -4, -5, -6, and -7), especially mcr-1, in carbapenem-resistant Enterobacteriaceae is a serious threat to global health. Here, we characterized a novel mobile colistin resistance gene, mcr-8, located on a transferrable 95,983-bp IncFII-type plasmid in Klebsiella pneumoniae. The deduced amino-acid sequence of MCR-8 showed 31.08%, 30.26%, 39.96%, 37.85%, 33.51%, 30.43%, and 37.46% identity to MCR-1, MCR-2, MCR-3, MCR-4, MCR-5, MCR-6, and MCR-7, respectively. Functional cloning indicated that the acquisition of the single mcr-8 gene significantly increased resistance to colistin in both Escherichia coli and K. pneumoniae. Notably, the coexistence of mcr-8 and the carbapenemase-encoding gene blaNDM was confirmed in K. pneumoniae isolates of livestock origin. Moreover, BLASTn analysis of mcr-8 revealed that this gene was present in a colistin- and carbapenem-resistant K. pneumoniae strain isolated from the sputum of a patient with pneumonia syndrome in the respiratory intensive care unit of a Chinese hospital in 2016. These findings indicated that mcr-8 has existed for some time and has disseminated among K. pneumoniae of both animal and human origin, further increasing the public health burden of antimicrobial resistance.
| S-EPMC6030107 | biostudies-literature
Project description:A novel mcr variant, named mcr-1.2, encoding a Gln3-to-Leu functional variant of MCR-1, was detected in a KPC-3-producing ST512 Klebsiella pneumoniae isolate collected in Italy from a surveillance rectal swab from a leukemic child. The mcr-1.2 gene was carried on a transferable IncX4 plasmid whose structure was very similar to that of mcr-1-bearing plasmids previously found in Escherichia coli and K. pneumoniae strains from geographically distant sites (Estonia, China, and South Africa).
| S-EPMC4997870 | biostudies-literature
Project description:Here, we report the description of a colistin-heteroresistant Klebsiella pneumoniae isolate fortuitously isolated from the stool sample of a patient with suspicion of tuberculosis in a public hospital of Marseille, France. In the colistin-resistant subpopulation, a mutation in the mgrB gene leading to a premature stop codon was found, and the hypermucoviscous phenotype was lost. Susceptibility to other antibiotics remained unchanged. To our knowledge, this is the first identification of such a colistin-heteroresistant Klebsiella pneumoniae isolate in France.
| S-EPMC5444162 | biostudies-literature
Project description:Colistin is one of the antibiotics of last resort for the treatment of carbapenem-resistant Klebsiella pneumoniae infection. This study showed that capsular type K64 (50%) and ST11 (53.9%) are the prevalent capsular and sequence types in the colistin-resistant strains in Taiwan. The interruption of transcripts (38.5%) and amino acid mutation (15.4%) in mgrB are the major mechanisms contributing to colistin resistance. In addition, novel single amino acid changes in MgrB (Stop48Tyr) and PhoQ (Leu26Pro) were observed to contribute to colistin resistance.
| S-EPMC4394772 | biostudies-literature
Project description:BackgroundThe prevalence of antimicrobial resistance (AMR) among Gram-negative bacteria is alarmingly high. Reintroduction of colistin as last resort treatment in the infections caused by drug-resistant Gram-negative bacteria has led to the emergence and spread of colistin resistance. This study was designed to determine the prevalence of drug-resistance among beta-lactamase-producing strains of Escherichia coli and Klebsiella pneumoniae, isolated from the clinical specimens received at a tertiary care centre of Kathmandu, Nepal during the period of March to August, 2019.MethodsA total of 3216 different clinical samples were processed in the Microbiology laboratory of Kathmandu Model Hospital. Gram-negative isolates (E. coli and K. pneumoniae) were processed for antimicrobial susceptibility test (AST) by using modified Kirby-Bauer disc diffusion method. Drug-resistant isolates were further screened for extended-spectrum beta-lactamase (ESBL), metallo-beta-lactamase (MBL), carbapenemase and K. pneumoniae carbapenemase (KPC) production tests. All the suspected enzyme producers were processed for phenotypic confirmatory tests. Colistin resistance was determined by minimum inhibitory concentration (MIC) using agar dilution method. Colistin resistant strains were further screened for plasmid-mediated mcr-1 gene using conventional polymerase chain reaction (PCR).ResultsAmong the total samples processed, 16.4% (529/3216) samples had bacterial growth. A total of 583 bacterial isolates were recovered from 529 clinical samples. Among the total isolates, 78.0% (455/583) isolates were Gram-negative bacteria. The most predominant isolate among Gram-negatives was E. coli (66.4%; 302/455) and K. pneumoniae isolates were 9% (41/455). In AST, colistin, polymyxin B and tigecycline were the most effective antibiotics. The overall prevalence of multidrug-resistance (MDR) among both of the isolates was 58.0% (199/343). In the ESBL testing, 41.1% (n = 141) isolates were confirmed as ESBL-producers. The prevalence of ESBL-producing E. coli was 43% (130/302) whereas that of K. pneumoniae was 26.8% (11/41). Similarly, 12.5% (43/343) of the total isolates, 10.9% (33/302) of E. coli and 24.3% of (10/41) K. pneumoniae were resistant to carbapenem. Among 43 carbapenem resistant isolates, 30.2% (13/43) and 60.5% (26/43) were KPC and MBL-producers respectively. KPC-producers isolates of E. coli and K. pneumoniae were 33.3% (11/33) and 20% (2/10) respectively. Similarly, 63.6% (21/33) of the E. coli and 50% (5/10) of the K. pneumoniae were MBL-producers. In MIC assay, 2.2% (4/179) of E. coli and 10% (2/20) of K. pneumoniae isolates were confirmed as colistin resistant (MIC ≥ 4 µg/ml). Overall, the prevalence of colistin resistance was 3.1% (6/199) and acquisition of mcr-1 was 16.6% (3/18) among the E. coli isolates.ConclusionHigh prevalence of drug-resistance in our study is indicative of a deteriorating situation of AMR. Moreover, significant prevalence of resistant enzymes in our study reinforces their roles in the emergence of drug resistance. Resistance to last resort drug (colistin) and the isolation of mcr-1 indicate further urgency in infection management. Therefore, extensive surveillance, formulation and implementation of effective policies, augmentation of diagnostic facilities and incorporation of antibiotic stewardship programs can be some remedies to cope with this global crisis.
| S-EPMC8256586 | biostudies-literature