title: Evaluation of resistance acquisition during tuberculosis treatment using whole genome sequencing.
abstract: Tuberculosis (TB) is still considered a major global public health problem in the world and there is a concern about the worldwide increase of drug-resistance (DR). This paper describes the analysis of three Mycobacterium tuberculosis isolates from a single patient collected over a long treatment period of time. DR was initially investigated through phenotypic testing, followed by line probe assays (LPAs) and whole genome sequencing (WGS). It presents an intriguing situation where a multidrug-resistant (MDR-) TB case was diagnosed and treated based only on late phenotypic drug susceptibility testing of isolate 1. During the treatment, another two isolates were cultivated: isolate 2, nine months after starting MDR-TB treatment; and isolate 3, cultivated five months later, during regular use of anti-TB drugs. These two isolates were evaluated using molecular LPA and WGS, retrospectively. All mutations detected by LPA were also detected in the WGS, including conversion from fluoroquinolones susceptibility to resistance from isolate 2 to isolate 3. WGS showed additional mutations, including some which may confer resistance to other drugs not tested (terizidone/cycloserine) and mutations with no correspondent resistance in drug susceptibility testing (streptomycin and second-line injectable drugs).
authors.affiliation: Department of Internal Medicine, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil.
authors.forename: Cinara
authors.initials: C
authors.lastname: Silva Feliciano
authors.affiliation: Center for Medical Genomics, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, Brazil.
authors.forename: Jessica
authors.initials: J
authors.lastname: Rodrigues Plaça
authors.affiliation: Department of Genetics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil; Center for Medical Genomics, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, Brazil.
authors.forename: Kamila
authors.initials: K
authors.lastname: Peronni
authors.affiliation: Department of Genetics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil; Center for Medical Genomics, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, Brazil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Araújo Silva
authors.affiliation: Department of Internal Medicine, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil; Center for Medical Genomics, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, Brazil. Electronic address: vbollela@gmail.com.
authors.forename: Valdes
authors.initials: V
authors.lastname: Roberto Bollela
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics; D004351:Drug Resistance; D054908:Extensively Drug-Resistant Tuberculosis / Q000235:genetics* / Q000382:microbiology; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D013997:Time Factors
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins
keywords: Drug resistant tuberculosis; Drug susceptibility tests; Tuberculosis; Whole genome sequencing