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Journal of Clinical Microbiology, July 2005, p. 3114-3120, Vol. 43, No. 7
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.7.3114-3120.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Drug Resistance Evolution of a Mycobacterium tuberculosis Strain from a Noncompliant Patient

Francesca Meacci,1 Germano Orrù,2 Elisabetta Iona,3 Federico Giannoni,3 Claudio Piersimoni,4 Gianni Pozzi,1 Lanfranco Fattorini,3 and Marco R. Oggioni1*

Dipartimento di Biologia Molecolare, Laboratorio di Microbiologia Molecolare e Biotecnologia, Università di Siena, Siena,1 Dipartimento di Scienze Odontostomatologiche, Universita' di Cagliari, Cagliari,2 Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, 00161 Roma,3 Dipartimento di Microbiologia Clinica, Ospedali Riuniti, Ancona, Italy4

Received 5 August 2004/ Returned for modification 24 September 2004/ Accepted 3 April 2005

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.

* Corresponding author. Mailing address: LAMMB, Università di Siena, Policlinico Le Scotte, lotto 5, piano 1, 53100 Siena, Italy. Phone: 0039 0577 233101. Fax: 0039 0577 233334. E-mail: oggioni{at}unisi.it.

Journal of Clinical Microbiology, July 2005, p. 3114-3120, Vol. 43, No. 7
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.7.3114-3120.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yesilkaya, H., Meacci, F., Niemann, S., Hillemann, D., Rusch-Gerdes, S., LONG DRUG Study Group, , Barer, M. R., Andrew, P. W., Oggioni, M. R. (2006). Evaluation of Molecular-Beacon, TaqMan, and Fluorescence Resonance Energy Transfer Probes for Detection of Antibiotic Resistance-Conferring Single Nucleotide Polymorphisms in Mixed Mycobacterium tuberculosis DNA Extracts.. J. Clin. Microbiol. 44: 3826-3829 [Abstract] [Full Text]  


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