-transparent.png){kind=logo}
Control of tuberculosis is threatened by widespread emergence of drug resistance in Mycobacterium tuberculosis. Understanding the molecular basis of resistance might lead to development of novel rapid methods for diagnosing drug resistance. We set out to determine the molecular basis of resistance to rifampicin, a major component of multidrug regimens used for treating tuberculosis. Resistance to rifampicin involves alterations of RNA polymerase. The gene that encodes the RNA polymerase subunit beta (rpoB) was cloned. Sequence information from this gene was used to design primers for direct amplification and sequencing of a 411 bp rpoB fragment from 122 isolates of M tuberculosis. Mutations involving 8 conserved aminoacids were identified in 64 of 66 rifampicin-resistant isolates of diverse geographical origin, but in none of 56 sensitive isolates. All mutations were clustered within a region of 23 aminoacids. Thus, substitution of a limited number of highly conserved aminoacids encoded by the rpoB gene appears to be the molecular mechanism responsible for "single step" high-level resistance to rifampicin in M tuberculosis. This information was used to develop a strategy (polymerase chain reaction-single-strand conformation polymorphism) that allowed efficient detection of all known rifampicin-resistant mutants. These findings provide the basis for rapid detection of rifampicin resistance, a marker of multidrug-resistant tuberculosis.
A Telenti, and
P Imboden, and
F Marchesi, and
D Lowrie, and
S Cole, and
M J Colston, and
L Matter, and
K Schopfer, and
T Bodmer
April 2011,
The Journal of antimicrobial chemotherapy,
A Telenti, and
P Imboden, and
F Marchesi, and
D Lowrie, and
S Cole, and
M J Colston, and
L Matter, and
K Schopfer, and
T Bodmer
January 2023,
International journal of mycobacteriology,
A Telenti, and
P Imboden, and
F Marchesi, and
D Lowrie, and
S Cole, and
M J Colston, and
L Matter, and
K Schopfer, and
T Bodmer
August 2001,
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology,
A Telenti, and
P Imboden, and
F Marchesi, and
D Lowrie, and
S Cole, and
M J Colston, and
L Matter, and
K Schopfer, and
T Bodmer
January 2018,
Journal of infection and public health,
A Telenti, and
P Imboden, and
F Marchesi, and
D Lowrie, and
S Cole, and
M J Colston, and
L Matter, and
K Schopfer, and
T Bodmer
July 2004,
The Journal of antimicrobial chemotherapy,
A Telenti, and
P Imboden, and
F Marchesi, and
D Lowrie, and
S Cole, and
M J Colston, and
L Matter, and
K Schopfer, and
T Bodmer
January 1996,
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde,
A Telenti, and
P Imboden, and
F Marchesi, and
D Lowrie, and
S Cole, and
M J Colston, and
L Matter, and
K Schopfer, and
T Bodmer
January 2012,
Polish journal of microbiology,
A Telenti, and
P Imboden, and
F Marchesi, and
D Lowrie, and
S Cole, and
M J Colston, and
L Matter, and
K Schopfer, and
T Bodmer
May 2016,
Annals of translational medicine,
A Telenti, and
P Imboden, and
F Marchesi, and
D Lowrie, and
S Cole, and
M J Colston, and
L Matter, and
K Schopfer, and
T Bodmer
January 2014,
Acta biochimica et biophysica Sinica,
A Telenti, and
P Imboden, and
F Marchesi, and
D Lowrie, and
S Cole, and
M J Colston, and
L Matter, and
K Schopfer, and
T Bodmer
August 2023,
Pathogens (Basel, Switzerland),
