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      Lipid A-Ara4N as an alternate pathway for (colistin) resistance in Klebsiella pneumonia isolates in Pakistan


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          This study aimed to explore mechanism of colistin resistance amongst Klebsiella pneumoniae isolates through plasmid mediated mcr-1 gene in Pakistan. Carbapenem and Colistin resistant K. pneumoniae isolates (n  = 34) stored at − 80 °C as part of the Aga Khan University Clinical Laboratory strain bank were randomly selected and subjected to mcr-1 gene PCR. To investigate mechanisms of resistance, other than plasmid mediated mcr-1 gene, whole genome sequencing was performed on 8 clinical isolates, including 6 with colistin resistance (MIC  >  4 μg/ml) and 2 with intermediate resistance to colistin (MIC  >  2 μg/ml).


          RT-PCR conducted revealed absence of mcr-1 gene in all isolates tested. Whole genome sequencing results revealed modifications in Lipid A-Ara4N pathway. Modifications in Lipid A-Ara4N pathway were detected in ArnA_ DH/FT, UgdH, ArnC and ArnT genes. Mutation in ArnA_ DH/FT gene were detected in S3, S5, S6 and S7 isolates. UgdH gene modifications were found in all isolates except S3, mutations in ArnC were present in all except S1, S2 and S8 and ArnT were detected in all except S4 and S7. In the absence of known mutations linked with colistin resistance, lipid pathway modifications may possibly explain the phenotype resistance to colistin, but this needs further exploration.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13104-021-05867-3.

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          Most cited references41

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          Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.

          Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae.
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            Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance.

            Klebsiella pneumoniae is an important multidrug-resistant (MDR) pathogen affecting humans and a major source for hospital infections associated with high morbidity and mortality due to limited treatment options. We summarize the wide resistome of this pathogen, which encompasses plentiful chromosomal and plasmid-encoded antibiotic resistance genes (ARGs). Under antibiotic selective pressure, K. pneumoniae continuously accumulates ARGs, by de novo mutations, and via acquisition of plasmids and transferable genetic elements, leading to extremely drug resistant (XDR) strains harboring a 'super resistome'. In the last two decades, numerous high-risk (HiR) MDR and XDR K. pneumoniae sequence types have emerged showing superior ability to cause multicontinent outbreaks, and continuous global dissemination. The data highlight the complex evolution of MDR and XDR K. pneumoniae, involving transfer and spread of ARGs, and epidemic plasmids in highly disseminating successful clones. With the worldwide catastrophe of antibiotic resistance and the urgent need to identify the main pathogens that pose a threat on the future of infectious diseases, further studies are warranted to determine the epidemic traits and plasmid acquisition in K. pneumoniae. There is a need for future genomic and translational studies to decipher specific targets in HiR clones to design targeted prevention and treatment.
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              Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates.

              A multilocus sequence typing (MLST) scheme was developed for Klebsiella pneumoniae. Sequences of seven housekeeping genes were obtained for 67 K. pneumoniae strains, including 19 ceftazidime- and ciprofloxacin-resistant isolates. Forty distinct allelic profiles were identified. MLST data were validated against ribotyping and showed high (96%) discriminatory power. The MLST approach provides unambiguous data useful for the epidemiology of K. pneumoniae isolates.

                Author and article information

                BMC Res Notes
                BMC Res Notes
                BMC Research Notes
                BioMed Central (London )
                14 December 2021
                14 December 2021
                : 14
                [1 ]GRID grid.7147.5, ISNI 0000 0001 0633 6224, Department of Pathology and Laboratory Medicine, , Aga Khan University, ; Karachi, Pakistan
                [2 ]GRID grid.8991.9, ISNI 0000 0004 0425 469X, Department of Infection Biology, Faculty Infectious and Tropical Diseases, , London School of Hygiene and Tropical Medicine, ; London, UK
                [3 ]Health Security Partners, Washington, DC 20009 USA
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                Funded by: Health Security Partners (HSP)-USA
                Research Note
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                © The Author(s) 2021

                klebsiella pneumonia,mcr-1 gene,antimicrobial drug resistance
                klebsiella pneumonia, mcr-1 gene, antimicrobial drug resistance


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