Possible genetic events producing colistin resistance gene mcr-1

Abstract

Yi-Yun Liu and colleagues1Liu Y-Y Wang Y Walsh TR et al.Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.Lancet Infect Dis. 2015; (published online Nov 18.)http://dx.doi.org/10.1016/S1473-3099(15)00424-7Google Scholar reported the sequence of the colistin resistance mcr-1 gene in plasmid pHNSHP45, flanked on 5' by insertion sequence (IS) Apl1 and the nikB gene, in this order. pHNSHP45 was isolated from Escherichia coli strain SHP45. Moreover, they noted that five E coli DNA contigs containing mcr-1-like genes from Malaysia had been recently submitted to the European Molecular and Biology Laboratory and provided the corresponding GenBank accession numbers. We further investigated these sequences and would like to add the following information. These contigs have been recently annotated by the NCBI Prokaryotic Genome Annotation Pipeline:2Tatusova T DiCuccio T Badretdin A et al.Prokaryotic Genome Annotation Pipeline, in The NCBI [internet] Handbook. 2nd edn. National Center for Biotechnology Information (US), Bethesda (MD)2013http://www.ncbi.nlm.nih.gov/books/NBK174280/Google Scholar all of them share with plasmid pHNSHP45 the identical mcr-1 coding sequence. Additionally, we also found this coding sequence within another DNA contig from Salmonella enterica (strain sl45). A summary is reported in the table.TableSummary information on the origin and features of identified sequences found in the NCBI RefSeq database as described in the text, by submitter (country, date)Biosample informationSpecies information, strainSequence informationCollection dateSample originIsolation sourceBiosample IDRefSeq ID: mcr-1 cds positionLength (bps)pHNSHP45 14Kb block present?ISApl1 upstream mcr-1 gene?ISApl1 in other contigs?University of Malaya (Malaysia, Dec 09, 2014)September, 2013Selangor, MalaysiaChicken liverSAMN03256216Escherichia coli, EC5NZ_JWKF01000084.1:4213-5838 (−)16 531YesNo, but nikB geneNoUniversity of Malaya (Malaysia, Dec 9, 2014)September, 2013Selangor, MalaysiaChicken spleenSAMN03256224E coli, EC7NZ_JWKG01000081.110696-12321 (+)16 534YesNo, but nikB geneNoUniversity of Malaya (Malaysia, Dec 9, 2014)September, 2013Selangor, MalaysiaWaterSAMN03256245E coli, EC13NZ_JUJZ01000081.1:8977-10602 (−)21 926YesNo, but nikB geneNoUniversity of Malaya (Malaysia, Dec 9, 2014)September, 2013Selangor, MalaysiaChicken heart and liverSAMN03256247E coli, EC2_1NZ_JWKJ01000115.1:213-1838 (+)8052NoYes, last 45 bpYesUniversity of Malaya (Malaysia, Dec 9, 2014)September, 2013Johor, MalaysiaPig faecal swabSAMN03256164E coli, EC2NZ_JWKC01000186.1:817-2442 (−)2648Downstream mcr-1 onlyYes, last 29 bpYesUniversity of Coimbra (Portugal, Dec 9, 2014)June, 2011Not reportedFood sampleSAMN03774870Salmonella enterica, Sa 125NZ_LFCC01000022.1:285-1910 (+)50 981NoYes, last 98 bpYesbp=base pairs. Open table in a new tab bp=base pairs. Sequences in the public NCBI database highly similar to these contigs (assessed by BLAST) are plasmids, an indirect indication that they are more probably of plasmid rather than genomic origin. An analysis of the alignments revealed that sequences of three of these contigs (E coli strains EC5, EC7, and EC13) share a region of about 14 Kb identical to plasmid pHNSHP45 spanning the mcr-1 gene and its neighbouring genes (99·999% identity), except for the ISApl1 element, which is absent. The ISApl1 is not present in other contigs of these three strains. Sequences of the other contigs (E coli strains EC2, EC2_1 and S enterica sl45) have only part of the ISApl1 flanking the 5' mcr-1 gene. When looking for ISApl1 in other contigs of these strains, we found short contigs (one per strain) containing exactly this IS, an indication that ISApl1 is probably present more than once and the assembling procedure was not able to untangle these repetition ambiguities. Only the sequence of the contig from strain EC2 is identical to that of pHNSHP45 downstream of the mcr-1 coding sequence. According to these findings, and to the fact that ISs are reported to be involved in both translocations and regulation of expression of flanking genes3Lopes BS Al-Agamy MH Ismail MA et al.The transferability of blaOXA523 gene in multidrug-resistant Acinetobacter baumannii isolates from Saudi Arabia and Egypt.Int J Med Microbiol. 2015; 305: 58158Crossref Scopus (34) Google Scholar, 4Al-Hassan L Opazo A Lopes BS El Mahallawy H Amyes SGB Variations in IS6 promoters alter the expression of carbapenem resistance in related strains of Acinetobacter baumannii.J Glob Antimicrob Resist. 2015; 3: 558Google Scholar we postulate that the mcr-1 gene is present in more E coli strains and for longer than expected, probably as part of plasmids, but without the ISApI1 transposable element. The insertion of this element on the region 5' of the mcr-1 gene might be the event triggering its rapid mobilisation on conjugating plasmids like pHNSHP45 and thus to other bacteria like salmonella. We declare no competing interests. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological studyThe emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Full-Text PDF