A novel marRAB operon contributes to the rifampicin resistance in Mycobacterium smegmatis.
A novel marRAB operon contributes to the rifampicin resistance in Mycobacterium smegmatis.
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DOI:
10.1371/journal.pone.0106016
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
He ZG
中科院分区:
文献类型:
--
作者:
Zhang H;Gao L;Zhang J;Li W;Yang M;Zhang H;Gao C;He ZG
The multiple-antibiotic resistance regulator (MarR) plays an important role in modulating bacterial antibiotic resistance. However, the regulatory model of the marRAB operon in mycobacteria remains to be characterized. Here we report that a MarR, encoded by Ms6508, and its marRAB operon specifically contribute to rifampicin (RIF) resistance in Mycobacterium smegmatis. We show that the MarR recognizes a conserved 21-bp palindromic motif and negatively regulates the expression of two ABC transporters in the operon, encoded by Ms6509–6510. Unlike other known drug efflux pumps, overexpression of these two ABC transporters unexpectedly increased RIF sensitivity and deletion of these two genes increased mycobacterial resistance to the antibiotic. No change can be detected for the sensitivity of recombinant mycobacterial strains to three other anti-TB drugs. Furthermore, HPLC experiments suggested that Ms6509–Ms6510 could pump RIF into the mycobacterial cells. These findings indicated that the mycobacterial MarR functions as a repressor and constitutively inhibits the expression of the marRAB operon, which specifically contributes to RIF resistance in M. smegmatis. Therefore, our data suggest a new regulatory mechanism of RIF resistance and also provide the new insight into the regulatory model of a marRAB operon in mycobacteria.
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影响因子:
14.9
作者:
Blokpoel MC;Murphy HN;O'Toole R;Wiles S;Runn ES;Stewart GR;Young DB;Robertson BD
通讯作者:
Robertson BD
DOI:
10.1073/pnas.92.12.5456
发表时间:
1995-06-06
影响因子:
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作者:
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作者:
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通讯作者:
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