Emergence of Mobile Colistin Resistance ( mcr-8 ) in a Highly Successful Klebsiella pneumoniae Sequence Type 15 Clone from Clinical Infections in Bangladesh

• Published in: mSphere 2020-03, Vol.5 (2)
• Main Authors: Farzana, Refath, Jones, Lim S, Barratt, Andrew, Rahman, Muhammad Anisur, Sands, Kirsty, Portal, Edward, Boostrom, Ian, Espina, Laura, Pervin, Monira, Uddin, A K M Nasir, Walsh, Timothy R
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial agents; Bacterial Proteins - genetics; Bangladesh; Bangladesh - epidemiology; Clinical Science and Epidemiology; Cloning; Colistin; Colistin - pharmacology; Deoxyribonucleic acid; DNA; Drug Resistance, Bacterial - genetics; E coli; Epidemiology; Genomes; Hospitals - statistics & numerical data; human; Humans; Infant, Newborn; Intensive care; Intubation; Kinases; Klebsiella Infections - epidemiology; Klebsiella Infections - microbiology; Klebsiella pneumoniae; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - genetics; Livestock; Male; mcr-8.1; Microbial Sensitivity Tests; Middle Aged; Multidrug resistance; Nosocomial infections; Observation; Phylogenetics; Phylogeny; Plasmids; Prevalence; Single-nucleotide polymorphism; Transposition
• ISSN: 2379-5042; 2379-5042
• DOI: 10.1128/msphere.00023-20

The emergence of mobilized colistin resistance genes ( ) has become a serious concern in clinical practice, compromising treatment options for life-threatening infections. In this study, colistin-resistant harboring was recovered from infected patients in the largest public hospital of Bangladesh, with a prevalence of 0.3% (3/1,097). We found in an identical highly stable multidrug-resistant IncFIB(pQil) plasmid of ∼113 kb, which belonged to an epidemiologically successful 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 in a Bangladeshi hospital. Core genome single-nucleotide polymorphisms among the -positive isolates ranged from 23 to 110. It has been hypothesized that was inserted into IncFIB(pQil) with preexisting resistance loci, and , by IS Coincidentally, all resistance determinants in the plasmid [ , , , , , , ] were bracketed by IS , demonstrating the possibility of intra- and interspecies and intra- and intergenus transposition of entire resistance loci. This is the first report of an -like mechanism from human infections in Bangladesh. However, given the acquisition of by a sable conjugative plasmid in a successful high-risk clone of ST15, there is a serious risk of dissemination of in Bangladesh from 2017 onwards. 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 in humans and livestock will increase in South Asia. Given the high prevalence of and in India, Bangladesh, and Pakistan, colistin has become the invariable option for the management of serious infections, leading to the emergence of -like mechanisms in South Asia. Systematic scrutiny of the prevalence and transmission of variants in South Asia is vital to understanding the drivers of genes and to initiate interventions to overcome colistin resistance.