Mycobacterium tuberculosis whole genome sequencing provides insights into the Manila strain and drug-resistance mutations in the Philippines.

Autor: Phelan JE; Infection Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK., Lim DR; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa City, Philippines.; TB Study Group, Research Institute for Tropical Medicine, Muntinlupa City, Philippines., Mitarai S; Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan., de Sessions PF; Genome Institute of Singapore, 60 Biopolis St, Biopolis, Singapore., Tujan MAA; Molecular Biology Laboratory, Research Institute for Tropical Medicine, Muntinlupa City, Philippines., Reyes LT; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa City, Philippines.; TB Study Group, Research Institute for Tropical Medicine, Muntinlupa City, Philippines., Medado IAP; Molecular Biology Laboratory, Research Institute for Tropical Medicine, Muntinlupa City, Philippines., Palparan AG; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa City, Philippines.; TB Study Group, Research Institute for Tropical Medicine, Muntinlupa City, Philippines., Naim ANM; Genome Institute of Singapore, 60 Biopolis St, Biopolis, Singapore., Jie S; Genome Institute of Singapore, 60 Biopolis St, Biopolis, Singapore., Segubre-Mercado E; Molecular Biology Laboratory, Research Institute for Tropical Medicine, Muntinlupa City, Philippines., Simoes B; Infection Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK., Campino S; Infection Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK., Hafalla JC; Infection Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK., Murase Y; Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan., Morishige Y; Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan., Hibberd ML; Infection Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK., Kato S; Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan., Ama MCG; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa City, Philippines.; TB Study Group, Research Institute for Tropical Medicine, Muntinlupa City, Philippines., Clark TG; Infection Biology Department, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. Taane.clark@lshtm.ac.uk.; Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. Taane.clark@lshtm.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Jun 26; Vol. 9 (1), pp. 9305. Date of Electronic Publication: 2019 Jun 26.
DOI: 10.1038/s41598-019-45566-5
Abstrakt: The Philippines has a high incidence of tuberculosis disease (TB), with an increasing prevalence of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) strains making its control difficult. Although the M. tuberculosis "Manila" ancient lineage 1 strain-type is thought to be prevalent in the country, with evidence of export to others, little is known about the genetic diversity of circulating strains. By whole genome sequencing (WGS) 178 isolates from the Philippines National Drug Resistance Survey, we found the majority (143/178; 80.3%) belonged to the lineage 1 Manila clade, with the minority belonging to lineages 4 (European-American; n = 33) and 2 (East Asian; n = 2). A high proportion were found to be multidrug-resistant (34/178; 19.1%), established through highly concordant laboratory drug susceptibility testing and in silico prediction methods. Some MDR-TB isolates had near identical genomic variation, providing potential evidence of transmission. By placing the Philippine isolates within a phylogeny of global M. tuberculosis (n > 17,000), we established that they are genetically similar to those observed outside the country, including a clade of Manila-like strain-types in Thailand. An analysis of the phylogeny revealed a set of ~200 SNPs that are specific for the Manila strain-type, and a subset can be used within a molecular barcode. Sixty-eight mutations known to be associated with 10 anti-TB drug resistance were identified in the Philippine strains, and all have been observed in other populations. Whilst nine putative streptomycin resistance conferring markers in gid (8) and rrs (1) genes appear to be novel and with functional consequences. Overall, this study provides an important baseline characterisation of M. tuberculosis genetic diversity for the Philippines, and will fill a gap in global datasets and aid the development of a nation-wide database for epidemiological studies and clinical decision making. Further, by establishing a molecular barcode for detecting Manila strains it will assist with the design of diagnostic tools for disease control activities.
Databáze: MEDLINE
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