Drug resistance evolution of a Mycobacterium tuberculosis strain from a noncompliant patient.
The emergence and spread of multidrug-resistant (MDR) Mycobacterium tuberculosis (MT) represents a worldwide health care problem because of the difficulty in treating these infections. Development of drug resistance in MT arises mainly by mutation of chromosomal genes. To investigate the evolution of a MT population during a long-lasting infection, the phenotypic and genotypic changes in the drug resistance of 10 sequential MT isolates from a noncompliant chronically infected patient were investigated. During more than 12 years of active disease, a MDR population developed; molecular typing showed one single parental strain that infected the patient and persisted throughout the disease. Molecular analysis of the drug resistance-related genes revealed that discrete subpopulations evolved over time from the parental strain by acquiring and accumulating resistance-conferring mutations to isoniazid, rifampin, and streptomycin. Overall, these observations indicate that during a chronic infection, several subpopulations may coexist in the same patient with different drug susceptibility profiles.
Dipartimento di Biologia Molecolare, Laboratorio di Microbiologia Molecolare e Biotecnologia, Università di Siena, Siena, Italy.
Francesca
F
Meacci
Germano
G
Orrù
Elisabetta
E
Iona
Federico
F
Giannoni
Claudio
C
Piersimoni
Gianni
G
Pozzi
Lanfranco
L
Fattorini
Marco R
MR
Oggioni
D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology*; D001483:Base Sequence; D002908:Chronic Disease; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D010349:Patient Compliance; D012269:Ribosomal Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology
D000995:Antitubercular Agents; D012269:Ribosomal Proteins; C034212:ribosomal protein S12