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Multidrug-resistant Tuberculosis pp 77–114Cite as

The molecular mechanisms of drug resistance in Mycobacterium tuberculosis

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Part of the book series: Resurgent and Emerging Infectious Diseases ((REID,volume 1))

Abstract

In the early 1990’s, when patients with acquired immunodeficiency syndrome (AIDS) in several large cities began dying with multidrugresistant (MDR) strains of Mycobacterium tuberculosis, there was considerable alarm and uncertainty [1,2]. The sudden and seemingly simultaneous appearance of many MDR strains raised the terrifying possibility that there was a single mechanism or mutation, perhaps carried on a plasmid or transposable element, that could confer resistance to several drugs and be transferred horizontally from strain to strain, as occurs in other bacteria [3,4]. Fears of “Andromeda-strain” scenarios receded after studies of MDR strains demonstrated that no single resistance mechanism was responsible. Rather, MDR strains were found to develop through the sequential occurrence of separate mutations, each conferring resistance to a single drug or class of drugs [5,6]. Finding the mutations that cause resistance to each of the antituberculosis drugs was a major focus of research in the 1990’s. The task was fairly straightforward for drugs that are also used against other pathogens, such as rifampicin (RIF), streptomycin (SM) and the fluoroquinolones (FQs), because the mechanisms were similar to those described in other bacteria. The real challenge was discovering the mutations that confer resistance to drugs that are specific for mycobacteria—isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB)—whose mechanisms of action were poorly understood. The study of the genes and mutations that cause resistance has not only unravelled the mechanisms of action of these antibiotics, but has also expanded our knowledge of the basic biology of the mycobacteria.

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  1. Laboratorio de Genética Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela

    Howard E. Takiff

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  1. Howard E. Takiff
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  1. Mycobacterium Reference Laboratory, Institute of Medical & Veterinary Science, Adelaide, Australia

    Ivan Bastian

  2. Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium

    Françoise Portaels

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© 2000 Springer Science+Business Media Dordrecht

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Takiff, H.E. (2000). The molecular mechanisms of drug resistance in Mycobacterium tuberculosis . In: Bastian, I., Portaels, F. (eds) Multidrug-resistant Tuberculosis. Resurgent and Emerging Infectious Diseases, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4084-3_6

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  • DOI: https://doi.org/10.1007/978-94-011-4084-3_6

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-5794-3

  • Online ISBN: 978-94-011-4084-3

  • eBook Packages: Springer Book Archive

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