Heterogeneity and Diversity of mcr-8 Genetic Context in Chicken-Associated Klebsiella pneumoniae

Abstract

Increasing mobile colistin resistance, mediated by the mcr gene family, in Enterobacteriaceae has become a global concern. Among the 10 reported mcr genes, mcr-8 was first identified in Klebsiella pneumoniae, which could cause severe infections with high mortality. Information about the prevalence and genetic context of mcr-8 is still lacking. In this study, we found that mcr-8 was present in 9.83% of K. pneumoniae of chicken origin. S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting showed that the mcr-8 gene was located on a plasmid in all the isolates. The genetic context of the plasmids exhibited considerable diversity from the whole genome sequence through Illumina and MinION long-read sequencing. Mutations in two-component systems may function synergistically with mcr-8, resulting in extremely high resistance to colistin. In addition to colistin resistance, these plasmids also contained genes conferring resistance to beta-lactams, tetracycline, aminoglycosides, sulfonamides, macrolides, chloramphenicol, and florfenicol. Therefore, these findings indicate that the genetic context of mcr-8 is heterogeneous and diverse, and that mcr-8 and certain chromosomal mechanisms may jointly contribute to high-level colistin resistance in K. pneumoniae strains, which provides new insights into the resistance mechanisms of K. pneumoniae.

Convergence of MCR-8.2 and chromosome-mediated resistance to colistin and tigecycline in an NDM-5-producing ST656 Klebsiella pneumoniae from a lung transplant patient

“…The D86E mutation has been described previously (43), while the other two mutations are reported for the first time. These results revealed that mcr-8.2 gene and chromosomal TCS may have synergistic effects in mediating bacterial resistance to colistin, as reported in a previous study (44).…”

Global Epidemiology and Genetic Environment of mcr genes: A One Health Systematic Review of Current and Emerging Trends

“…Yang et al (2019b) 122 found that the insertion of ISEcl7 was an independent event and may not be involved in mobilising mcr-8. The formation of circular intermediates via IS903B elements to mobilise mcr-8 remains unknown; however, the association of mcr-8 to ISs facilitates both the transmission of mcr-8 and its close association with other resistance genes 121 ; specifically, it has been found associated with aminoglycoside resistance genes 121 , β-lactamase genes 119 and tmexCD1-toprJ1 genes that encode a novel plasmid-mediated efflux pump that confers resistance to tigecycline 123 Mcr-8 is commonly found in K. pneumoniae 118,120,121,[123][124][125][126] , Wang et al (2018c) 118 performed a phylogenetic analysis of the mcr-positive K. pneumoniae isolates identified in their study and found that the mcr-positive K. pneumoniae were genetically diverse. K. pneumoniae express colistin resistance usually through chromosomal mutations 10 .…”

“…K. pneumoniae express colistin resistance usually through chromosomal mutations 10 . Wu et al (2020) 121 suggest the expression of mcr-8 may have synergistic effects with the chromosomal mutations within the two-component system (TCSs), resulting in heterogenous colistin resistance mechanisms 121 . Mcr-8 has also been identified in Klebsiella quasipneumoniae 122 Typhimurium isolated from a human patient in Washington State in 2010.…”

Novos aspectos do efeito antibacteriano de galectinas ligantes de lipopolissacarídeo

“…Yu et al 2015). Soma-se a isso a importância de que as propriedades antibacterianas de Gal-4 e Gal-3 independem da presença do gene mcr-1, que vem sendo alvo de preocupação da comunidade médica e científica nos últimos anos por conferir resistência a um último recurso terapêutico e, assim, preencher uma lacuna no repertório de mecanismos de ação antibacterianos contemplados em bactérias MDR (Liu et al 2016;García-Meniño et al 2019;Wu et al 2021). Ainda, as diversas alterações promovidas pelos sistemas de dois tanto pela natureza da afinidade de ligação, como pelas diferenças nas propriedades de oligomerização e estabilização de ligantes, favorecem esta classe de lectinas em detrimento aos anticorpos para a potencialização dos efeitos da PmB.…”

“…Considerando a alta toxicidade observada para tratamentos com PmB na clínica (Biswas et al 2012), diversos trabalhos procuraram avaliar a associação desse antibiótico com outros agentes antimicrobianos (Hollmann et al 2018) amostras clínicas e pecuárias de diversos países (Doumith et al 2016;Moon et al 2020;García-Meniño et al 2019) sendo descritos, até o momento, 10 membros dessa família de genes (Wu et al 2021).…”