title: Genomic epidemiology of multidrug-resistant Mycobacterium tuberculosis during transcontinental spread.
abstract: The transcontinental spread of multidrug-resistant (MDR) tuberculosis is poorly characterized in molecular epidemiologic studies. We used genomic sequencing to understand the establishment and dispersion of MDR Mycobacterium tuberculosis within a group of immigrants to the United States. We used a genomic epidemiology approach to study a genotypically matched (by spoligotype, IS6110 restriction fragment length polymorphism, and mycobacterial interspersed repetitive units-variable number of tandem repeat signature) lineage 2/Beijing MDR strain implicated in an outbreak of tuberculosis among refugees in Thailand and consecutive cases within California. All 46 MDR M. tuberculosis genomes from both Thailand and California were highly related, with a median difference of 10 single-nucleotide polymorphisms (SNPs). The Wat Tham Krabok (WTK) strain is a new sequence type distinguished from all known Beijing strains by 55 SNPs and a genomic deletion (Rv1267c) associated with increased fitness. Sequence data revealed a highly prevalent MDR strain that included several closely related but distinct allelic variants within Thailand, rather than the occurrence of a single outbreak. In California, sequencing data supported multiple independent introductions of WTK with subsequent transmission and reactivation within the state, as well as a potential super spreader with a prolonged infectious period. Twenty-seven drug resistance-conferring mutations and 4 putative compensatory mutations were found within WTK strains. Genomic sequencing has substantial epidemiologic value in both low- and high-burden settings in understanding transmission chains of highly prevalent MDR strains.
authors.affiliation: Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute University of Basel, Switzerland.
authors.forename: Mireia
authors.initials: M
authors.lastname: Coscolla
authors.affiliation: Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond.
authors.forename: Pennan M
authors.initials: PM
authors.lastname: Barry
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: John E
authors.initials: JE
authors.lastname: Oeltmann
authors.affiliation: Eureka Genomics, Hercules.
authors.forename: Heather
authors.initials: H
authors.lastname: Koshinsky
authors.affiliation: Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond.
authors.forename: Tambi
authors.initials: T
authors.lastname: Shaw
authors.affiliation: Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond.
authors.forename: Martin
authors.initials: M
authors.lastname: Cilnis
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Jamie
authors.initials: J
authors.lastname: Posey
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Francis J. Curry International Tuberculosis Center, San Francisco General Hospital, University of California.
authors.forename: Jordan
authors.initials: J
authors.lastname: Rose
authors.affiliation: Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond.
authors.forename: Terry
authors.initials: T
authors.lastname: Weber
authors.affiliation: Eureka Genomics, Hercules.
authors.forename: Viacheslav Y
authors.initials: VY
authors.lastname: Fofanov
authors.affiliation: Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute University of Basel, Switzerland.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Francis J. Curry International Tuberculosis Center, San Francisco General Hospital, University of California.
authors.forename: Midori
authors.initials: M
authors.lastname: Kato-Maeda
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Francis J. Curry International Tuberculosis Center, San Francisco General Hospital, University of California.
authors.forename: John Z
authors.initials: JZ
authors.lastname: Metcalfe
mesh_terms: D002140:California; D004196:Disease Outbreaks; D016680:Genome, Bacterial; D005838:Genotype; D006801:Humans; D017720:Molecular Epidemiology; D058889:Molecular Typing; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D010802:Phylogeny; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D013785:Thailand; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology / Q000382:microbiology*
keywords: EmbR; Mycobacterium tuberculosis; drug resistance; epidemiology; genomics