OBJECTIVES: Extensively drug-resistant (XDR) tuberculosis (TB) threatens the global control of TB worldwide. Lisbon has a high XDR-TB rate [50% of the multidrug-resistant tuberculosis (MDR-TB)], which is mainly associated with Lisboa family strains. Few studies have addressed the identification of mutations associated with resistance to second-line injectable drugs, and the relative frequency of such mutations varies geographically. The aim of this study was to characterize the genetic changes associated with the high number of XDR-TB cases in Lisbon. METHODS: In the present study we analysed 26 XDR-TB clinical isolates. The gyrA, tlyA and rrs genes were screened for mutations that could be responsible for resistance to fluoroquinolones and second-line injectable drugs. Moreover, the strains under analysis were also genotyped by MIRU-VNTR ('mycobacterial interspersed repetitive unit-variable number of tandem repeats'). RESULTS: The mutational analysis identified the most frequent mutations in the resistance-associated genes: S91P in gyrA (42.3%); A1401G in rrs (30.8%); and Ins755GT in tlyA (42.3%). The occurrence of mutations in rrs was associated with the non-occurrence of mutations in tlyA. The genotypic analysis revealed that the strains were highly clonal, belonging to one of two MIRU-VNTR clusters, with the largest belonging to the Lisboa family. Association between mutations in gyrA and rrs or tlyA was verified. CONCLUSIONS: The association of specific mutations highlighted the strains' high clonality and indicates recent XDR-TB transmission. In addition, the identification of the most frequent resistance-associated mutations will be invaluable in applying XDR-TB molecular detection tests in the region in the near future.
OBJECTIVES: Extensively drug-resistant (XDR) tuberculosis (TB) threatens the global control of TB worldwide. Lisbon has a high XDR-TB rate [50% of the multidrug-resistant tuberculosis (MDR-TB)], which is mainly associated with Lisboa family strains. Few studies have addressed the identification of mutations associated with resistance to second-line injectable drugs, and the relative frequency of such mutations varies geographically. The aim of this study was to characterize the genetic changes associated with the high number of XDR-TB cases in Lisbon. METHODS: In the present study we analysed 26 XDR-TB clinical isolates. The gyrA, tlyA and rrs genes were screened for mutations that could be responsible for resistance to fluoroquinolones and second-line injectable drugs. Moreover, the strains under analysis were also genotyped by MIRU-VNTR ('mycobacterial interspersed repetitive unit-variable number of tandem repeats'). RESULTS: The mutational analysis identified the most frequent mutations in the resistance-associated genes: S91P in gyrA (42.3%); A1401G in rrs (30.8%); and Ins755GT in tlyA (42.3%). The occurrence of mutations in rrs was associated with the non-occurrence of mutations in tlyA. The genotypic analysis revealed that the strains were highly clonal, belonging to one of two MIRU-VNTR clusters, with the largest belonging to the Lisboa family. Association between mutations in gyrA and rrs or tlyA was verified. CONCLUSIONS: The association of specific mutations highlighted the strains' high clonality and indicates recent XDR-TB transmission. In addition, the identification of the most frequent resistance-associated mutations will be invaluable in applying XDR-TB molecular detection tests in the region in the near future.
Authors: Fernanda Maruri; Timothy R Sterling; Anne W Kaiga; Amondrea Blackman; Yuri F van der Heijden; Claudine Mayer; Emmanuelle Cambau; Alexandra Aubry Journal: J Antimicrob Chemother Date: 2012-01-25 Impact factor: 5.790
Authors: Claudio U Köser; Silke Feuerriegel; David K Summers; John A C Archer; Stefan Niemann Journal: Antimicrob Agents Chemother Date: 2012-09-24 Impact factor: 5.191
Authors: Violet N Chihota; Borna Müller; Charmaine K Mlambo; Manormoney Pillay; Marisa Tait; Elizabeth M Streicher; Else Marais; Gian D van der Spuy; Madeleine Hanekom; Gerrit Coetzee; Andre Trollip; Cindy Hayes; Marlein E Bosman; Nico C Gey van Pittius; Tommie C Victor; Paul D van Helden; Robin M Warren Journal: J Clin Microbiol Date: 2011-12-14 Impact factor: 5.948
Authors: Sophia B Georghiou; Marisa Magana; Richard S Garfein; Donald G Catanzaro; Antonino Catanzaro; Timothy C Rodwell Journal: PLoS One Date: 2012-03-29 Impact factor: 3.240
Authors: Borna Müller; Violet N Chihota; Manormoney Pillay; Marisa Klopper; Elizabeth M Streicher; Gerrit Coetzee; Andre Trollip; Cindy Hayes; Marlein E Bosman; Nicolaas C Gey van Pittius; Thomas C Victor; Sebastien Gagneux; Paul D van Helden; Robin M Warren Journal: PLoS One Date: 2013-08-23 Impact factor: 3.240