
Dynamics of Antibiotic Resistant Mycobacterium tuberculosis during Long-Term Infection and Antibiotic Treatment
Author(s) -
Solomon H. Mariam,
Jim Werngren,
Joakim Aronsson,
Sven Hoffner,
Dan I. Andersson
Publication year - 2011
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0021147
Subject(s) - antibiotics , mycobacterium tuberculosis , antibiotic resistance , biology , tuberculosis , microbiology and biotechnology , drug resistance , population , medicine , environmental health , pathology
For an infecting bacterium the human body provides several potential ecological niches with both internally (e.g. host immunity) and externally (e.g. antibiotic use) imposed growth restrictions that are expected to drive adaptive evolution in the bacterium, including the development of antibiotic resistance. To determine the extent and pattern of heterogeneity generated in a bacterial population during long-term antibiotic treatment, we examined in a monoclonal Mycobacterium tuberculosis infection antibiotic resistant mutants isolated from one patient during a 9-years period. There was a progressive accumulation of resistance mutations in the infecting clone. Furthermore, apparent clonal sweeps as well as co-existence of different resistant mutants were observed during this time, demonstrating that during treatment there is a high degree of dynamics in the bacterial population. These findings have important implications for diagnostics and treatment of drug resistant tuberculosis infections.