In:
Chemotherapy, S. Karger AG, Vol. 58, No. 5 ( 2012), p. 341-348
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Intrinsic multidrug resistance of the 〈 i 〉 Mycobacterium avium 〈 /i 〉 - 〈 i 〉 intracellulare 〈 /i 〉 complex presents a serious problem in the treatment of the diseases caused by these bacteria. Recently, it was shown that deletion of a polyketide synthase, Pks12, in an 〈 i 〉 M. avium 〈 /i 〉 laboratory strain decreases this intrinsic resistance. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We investigated Pks12 expression and its enzymatic activity in 9 clinical isolates of 〈 i 〉 M. intracellulare 〈 /i 〉 , and compared their drug susceptibilities to 4 drugs. Also, we made 〈 i 〉 pks12 〈 /i 〉 -disrupted 〈 i 〉 M. bovis 〈 /i 〉 bacillus Calmette-Guérin (BCG) mutant and its complemented strain. Using these BCG and 〈 i 〉 M. intracellulare 〈 /i 〉 strains, we observed intracellular accumulation of ethidium bromide (EtBr). 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We found positive correlations between Pks12 and drug resistance for all of the antibiotics tested. The drug susceptible 〈 i 〉 M. intracellulare 〈 /i 〉 strain showed higher EtBr accumulation. Consistent with this, EtBr was much more accumulated in 〈 i 〉 pks12 〈 /i 〉 -disrupted BCG than wild-type or the complemented strains. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Collectively, these results suggest that Pks12 controls the multidrug resistance in part through intracellular drug accumulation.
Type of Medium:
Online Resource
ISSN:
0009-3157
,
1421-9794
Language:
English
Publisher:
S. Karger AG
Publication Date:
2012
detail.hit.zdb_id:
1482111-4
SSG:
15,3
