Dynamics of antibiotic resistant Mycobacterium tuberculosis during long-term infection and antibiotic treatment

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 re...

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Bibliographic Details
Published in:PloS one 2011-06, Vol.6 (6), p.e21147-e21147
Main Authors: Mariam, Solomon H, Werngren, Jim, Aronsson, Joakim, Hoffner, Sven, Andersson, Dan I
Format: Article
Language:English
Subjects:
Antibiotic resistance
Antibiotics
Antitubercular Agents - therapeutic use
Bacteria
Bacterial infections
Biology
Cloning
Disease control
Drug resistance
Drug Resistance, Microbial - genetics
Ecological niches
Evolution
Gene expression
Health aspects
Helicobacter pylori
Hospitals
Humans
Immunity
Infections
Infectious diseases
MEDICIN
MEDICINE
Microbial drug resistance
Microbial Sensitivity Tests
Mutagenesis
Mutants
Mutation
Mycobacterium smegmatis
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - genetics
Niches
Patients
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Population
Resistant mutant
Salmonella
Salmonella Typhimurium
Staphylococcus aureus
Streptomycin - therapeutic use
Tuberculosis
Tuberculosis, Multidrug-Resistant - drug therapy
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0021147