title: Occurrence of diverse mutations in isoniazid- and rifampicin-resistant Mycobacterium tuberculosis isolates from autochthonous and immigrant populations of Saudi Arabia.
abstract: For the first time in Saudi Arabia, the impact of a patient's ethnic background on mutations conferring resistance to rifampicin (RIF) and isoniazid (INH) in Mycobacterium tuberculosis isolates was analyzed on a nationwide sample collection. Four hundred fifteen isolates were subjected to drug susceptibility testing, mutation analysis, spoligotyping, and 24 loci-based Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeat typing, respectively. Phenotypically, 41 (9.9%) isolates were resistant to RIF, 239 (57.6%) to INH, and 135 (32.5%) to both RIF and INH, respectively. Forty (9.6%), 236 (56.8%), and 133 (32%) isolates were determined as resistant to RIF, INH, and to both by molecular assay. Codon 531 (S531L) mutations (69.4%) in the rpoB gene and codon 315 (S315T) mutations (67.2%) in the katG gene were the most prominent among RIF- and INH-resistant isolates, respectively. The autochthonous population showed a predominance of rpoB codon 516 and 526 mutations, while the inhA promoter position -15 and -8 mutations were prominent among immigrants. A strain cluster ratio of 32% (30 clusters) was observed and 24 clusters displayed identical mutations. Overall, Euro-American lineages were predominant. However, Beijing (56.7%) and EAI (42.7%) were noticed with the highest cluster rate. In Saudi Arabia, the occurrence of mutations responsible for INH and RIF resistance was significantly associated with the ethnic origin of the patient.
authors.affiliation: 1 Mycobacteriology Research Section, Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia .
authors.forename: Bright
authors.initials: B
authors.lastname: Varghese
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shoukri
authors.forename: Ziad
authors.initials: Z
authors.lastname: Memish
authors.forename: Naila
authors.initials: N
authors.lastname: Abuljadayel
authors.forename: Raafat
authors.initials: R
authors.lastname: Alhakeem
authors.forename: Fahad
authors.initials: F
authors.lastname: Alrabiah
authors.forename: Sahal
authors.initials: S
authors.lastname: Al-Hajoj
mesh_terms: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics; D003062:Codon / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D054242:Emigrants and Immigrants; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D012293:Rifampin / Q000627:therapeutic use*; D012529:Saudi Arabia; D018088:Tuberculosis, Multidrug-Resistant / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D001426:Bacterial Proteins; D003062:Codon; D004269:DNA, Bacterial; D007538:Isoniazid; D012293:Rifampin