title: Dynamics of antibiotic resistant Mycobacterium tuberculosis during long-term infection and antibiotic treatment.
abstract: 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.
authors.affiliation: Swedish Institute for Infectious Disease Control, Solna, Sweden.
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Mariam
authors.forename: Jim
authors.initials: J
authors.lastname: Werngren
authors.forename: Joakim
authors.initials: J
authors.lastname: Aronsson
authors.forename: Sven
authors.initials: S
authors.lastname: Hoffner
authors.forename: Dan I
authors.initials: DI
authors.lastname: Andersson
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013307:Streptomycin / Q000627:therapeutic use; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D013307:Streptomycin