title: Molecular characterization of Mycobacterium tuberculosis strains resistant to isoniazid.
abstract: OBJECTIVE
  Tuberculosis is a major public health problem and the emergence of drug resistance complicates the situation even more. It is therefore crucial to implement all conclusions from the studies that aim at a better understanding of the molecular mechanisms which govern the emergence and the evolution of drug resistance. The aim of this study is to assess the degree of involvement of the inhA and katG genes in the acquisition of isoniazid resistance in clinical strains of Mycobacterium tuberculosis.
  
  
  METHODS
  The inhA and katG genes were sequenced in 21 strains of M. tuberculosis with different resistance profiles and from different regions.
  
  
  RESULTS
  Analysis of the sequences obtained by comparison to those of the reference strain H37Rv showed that 95.2% had mutations. KatG S315T was the most common mutation (85.7%). The mutation katG T275A was revealed in two strains (9.5%). Two different point mutations in the inhA gene and its promoter region were identified as C-15T and G56A at a frequency equal to 14% and 10%, respectively. The G56A mutation is a new silent mutation. Our study showed no correlation between found mutations and multidrug resistance. Among the 21 strains studied, only one strain showed no mutations.
  
  
  CONCLUSIONS
  In terms of this study, we characterized the mutations involved in resistance to isoniazid. katG S315T was by far the most frequent mutation, followed by C-15T. The frequency of these mutations was concordant with those reported in literature including those in intermediate tuberculosis endemic countries.
authors.affiliation: Regional Laboratory of Hygiene, Sfax, Tunisia; Faculty of Pharmacy, Monastir, Tunisia. Electronic address: smaoui_salma@yahoo.fr.
authors.forename: Salma
authors.initials: S
authors.lastname: Smaoui
authors.affiliation: Preparatory Institute for Engineering Studies, Sfax, Tunisia.
authors.forename: Mariem
authors.initials: M
authors.lastname: Siala
authors.affiliation: Laboratory of Clinical Biochemistry, Children's Hospital, Tunis, Tunisia.
authors.forename: Sondes
authors.initials: S
authors.lastname: Hadj Fredj
authors.affiliation: Regional Laboratory of Hygiene, Sfax, Tunisia; Faculty of Pharmacy, Monastir, Tunisia.
authors.forename: Sana
authors.initials: S
authors.lastname: Kammoun
authors.affiliation: Regional Laboratory of Hygiene, Sfax, Tunisia; Faculty of Pharmacy, Monastir, Tunisia.
authors.forename: Chema
authors.initials: C
authors.lastname: Marouane
authors.affiliation: Regional Laboratory of Hygiene, Sfax, Tunisia; Faculty of Pharmacy, Monastir, Tunisia.
authors.forename: Salma
authors.initials: S
authors.lastname: Hachicha
authors.affiliation: Regional Laboratory of Hygiene, Sfax, Tunisia; Faculty of Pharmacy, Monastir, Tunisia.
authors.forename: Asma
authors.initials: A
authors.lastname: Ghorbel
authors.affiliation: Toxicology-Microbiology and Environmental Health Unit (UR11ES70), Faculty of Sciences, University of Sfax, Sfax, Tunisia.
authors.forename: Radhouane
authors.initials: R
authors.lastname: Gdoura
authors.affiliation: Microbiology Laboratory, Pneumology Hospital, Sfax, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Slim
authors.affiliation: Laboratory of Clinical Biochemistry, Children's Hospital, Tunis, Tunisia.
authors.forename: Taieb
authors.initials: T
authors.lastname: Ben Messaoud
authors.affiliation: Regional Laboratory of Hygiene, Sfax, Tunisia; Faculty of Pharmacy, Monastir, Tunisia.
authors.forename: Férièle
authors.initials: F
authors.lastname: Messadi
keywords: Isoniazid; Mutation; Mycobacterium tuberculosis; Resistance