The evolution of drug resistance in Mycobacterium tuberculosis: from a mono-rifampin-resistant cluster into increasingly multidrug-resistant variants in an HIV-seropositive population.
We describe the genotypic and phenotypic characteristics of a mono-rifampin-resistant (RIF(R)) Mycobacterium tuberculosis strain cluster (designated AU-RIF(R)) and the acquisition of additional drug resistance. Drug susceptibility, sequences of regions that determine drug resistance, and basic clinical data were examined. A rare codon duplication (514(TTC)) in rpoB conferring high levels of RIF(R) (minimum inhibitory concentration of >256 microg/mL) in 29 isolates was identified. AU-RIF(R) strains developed secondary resistance to isoniazid and 7 resistance combinations to 6 different antibiotics. Patients infected with AU-RIF(R) strains were primarily immunocompromised. These data suggest that host factors, such as HIV status, may allow dissemination of mono-RIF(R) strains and facilitate the accumulation of additional drug resistance.
Bifani
Pablo
P
Pasteur Institute, Brussels, Belgium. pbifani@pasteur.be
Mathema
Barun
B
Kurepina
Natalia
N
Shashkina
Elena
E
Bertout
Julie
J
Blanchis
Anne Sophie
AS
Moghazeh
Soraya
S
Driscoll
Jeffrey
J
Gicquel
Brigitte
B
Frothingham
Richard
R
Kreiswirth
Barry N
BN
D000995:Antitubercular Agents / Q000494:pharmacology*; D005075:Biological Evolution; D024901:Drug Resistance, Multiple, Bacterial; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D012293:Rifampin / Q000494:pharmacology*; D013997:Time Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology*
D000995:Antitubercular Agents; D012293:Rifampin