OBJECTIVES: The aim of this study was to clarify the conflicting data regarding cross-resistance and drug-resistance mechanisms for the cyclic peptide capreomycin and the aminoglycosides amikacin and kanamycin by comparing genotypes and phenotypes of clinical isolates and in vitro selected mutants of Mycobacterium tuberculosis. METHODS: The genes rrs and tlyA and the promoter region of eis of 152 M. tuberculosis clinical isolates (including 55 capreomycin resistant) and 44 in vitro selected capreomycin-, amikacin- and kanamycin-resistant mutants were sequenced. In addition, MICs of capreomycin, amikacin and kanamycin on Middlebrook 7H10 were determined. RESULTS: The results clearly show major differences in genotypes and cross-resistance patterns to amikacin and kanamycin between the capreomycin-resistant clinical isolates and in vitro selected mutants. tlyA mutations were found almost exclusively among the in vitro selected capreomycin-resistant mutants, while only four were found among the clinical isolates, of which two were capreomycin susceptible. In contrast, 53 of the 55 capreomycin-resistant clinical isolates had a mutation at position 1401 in rrs and were resistant to capreomycin, amikacin and kanamycin. Low-level resistance to kanamycin was correlated to mutations in the promoter region of eis. CONCLUSIONS: Our findings are consistent with the belief that a mutation at position 1401 in rrs leads to resistance to capreomycin, amikacin and kanamycin. The data also show that tlyA is not a sensitive genetic marker for capreomycin resistance in clinical isolates of M. tuberculosis, as mutations in this gene are infrequent and not all mutations in tlyA lead to capreomycin resistance.
OBJECTIVES: The aim of this study was to clarify the conflicting data regarding cross-resistance and drug-resistance mechanisms for the cyclic peptide capreomycin and the aminoglycosidesamikacin and kanamycin by comparing genotypes and phenotypes of clinical isolates and in vitro selected mutants of Mycobacterium tuberculosis. METHODS: The genes rrs and tlyA and the promoter region of eis of 152 M. tuberculosis clinical isolates (including 55 capreomycin resistant) and 44 in vitro selected capreomycin-, amikacin- and kanamycin-resistant mutants were sequenced. In addition, MICs of capreomycin, amikacin and kanamycin on Middlebrook 7H10 were determined. RESULTS: The results clearly show major differences in genotypes and cross-resistance patterns to amikacin and kanamycin between the capreomycin-resistant clinical isolates and in vitro selected mutants. tlyA mutations were found almost exclusively among the in vitro selected capreomycin-resistant mutants, while only four were found among the clinical isolates, of which two were capreomycin susceptible. In contrast, 53 of the 55 capreomycin-resistant clinical isolates had a mutation at position 1401 in rrs and were resistant to capreomycin, amikacin and kanamycin. Low-level resistance to kanamycin was correlated to mutations in the promoter region of eis. CONCLUSIONS: Our findings are consistent with the belief that a mutation at position 1401 in rrs leads to resistance to capreomycin, amikacin and kanamycin. The data also show that tlyA is not a sensitive genetic marker for capreomycin resistance in clinical isolates of M. tuberculosis, as mutations in this gene are infrequent and not all mutations in tlyA lead to capreomycin resistance.
Authors: J A Dijkstra; T van der Laan; O W Akkerman; M S Bolhuis; W C M de Lange; J G W Kosterink; T S van der Werf; J W C Alffenaar; D van Soolingen Journal: Antimicrob Agents Chemother Date: 2018-02-23 Impact factor: 5.191
Authors: Nontuthuko E Maningi; Luke T Daum; John D Rodriguez; Halima M Said; Remco P H Peters; John Osei Sekyere; Gerald W Fischer; James P Chambers; P Bernard Fourie Journal: J Clin Microbiol Date: 2018-04-25 Impact factor: 5.948
Authors: Matt Hoshide; Lishi Qian; Camilla Rodrigues; Rob Warren; Tommie Victor; Henry B Evasco; Thelma Tupasi; Valeriu Crudu; James T Douglas Journal: J Clin Microbiol Date: 2013-06-19 Impact factor: 5.948
Authors: Timothy C Rodwell; Faramarz Valafar; James Douglas; Lishi Qian; Richard S Garfein; Ashu Chawla; Jessica Torres; Victoria Zadorozhny; Min Soo Kim; Matt Hoshide; Donald Catanzaro; Lynn Jackson; Grace Lin; Edward Desmond; Camilla Rodrigues; Kathy Eisenach; Thomas C Victor; Nazir Ismail; Valeru Crudu; Maria Tarcela Gler; Antonino Catanzaro Journal: J Clin Microbiol Date: 2013-12-18 Impact factor: 5.948