C2-1981. High Frequency of embB Codon 406 Mutations in Ethambutol-Resistant Isolates of Mycobacterium tuberculosis
Session: Poster Session: Resistance in Mycobacteria
Monday, October 27, 2008: 12:00 AM
Room: Hall C
Background: The presence of mutations at codon 306 of embB gene (embB306) has been proposed as a major predictor of resistance to ethambutol (EMB) in M. tuberculosis (MT). Mutations at other embB codons, including position 406 (embB406), are less frequent. Recent reports have questioned the role of embB306 mutations in the degree of EMB resistance. The aim of this collaborative study was to determine the proportion of embB306 and embB406 mutations in EMB-resistant isolates of MT, and the occurrence of embB306 mutations in EMB-susceptible strains as well as the association with resistance to other drugs. Methods: Mutations in the embB gene (codons 282-421) of 33 EMB-resistant MT isolates were detected by sequencing. Twenty-six of them were multidrug-resistant MT (MDR-TB). Moreover, 78 EMB-susceptible isolates (25 MDR-TB) were screened for embB306 mutations by PCR-RFLP, and mutated strains were confirmed by sequencing. Results: Fifteen EMB-resistant strains (45.5%) presented embB mutations: 6 at embB306, 8 at embB406, and one strain showed a double substitution (embB306 and embB406). Among EMB-resistant isolates, 100% of embB406, 71.4% of embB306, and 47.1% of the remaining strains were MDR-TB. Seven (87.5%) embB406 strains and 3 (50%) embB306 strains required the highest inhibitory concentration of EMB (15 mg/L). Two of 78 (2.6%) EMB-susceptible strains showed embB306 mutations; both were MDR-TB. Conclusions: The embB406 mutations were more prevalent than embB306 in EMB-resistant MT isolated in Catalonia, in contrast to reports in other geographical areas. The embB406 MT strains showed a slightly higher level of phenotypic resistance to EMB than embB306 isolates. Some association between embB mutants, especially embB406, and MDR-TB was observed.
Nuria Martín-Casabona1, Pere Coll2, Raquel Moure3, Rosa Fernández4, Virginie Mick3, Ana Andreu3, Emma Rey5, Esmeralda Castelblanco3, Fernando Alcaide6, Griselda Tudó5, Margarita Salvado7, Michel Montemayor2 and  F. Alcaide, None., (1)Hosp. Vall d'Hebron, (2)Hosp. Sant Pau, (3)Hosp. Bellvitge, (4)Lab. de Referčncia de Catalunya, (5)Hosp. Clinic, (6)Hosp. Bellvitge, L'Hospitalet de Ll (Barcelona), Spain, (7)Hospital Del Mar


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