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Impaired fitness of Mycobacterium tuberculosis resistant isolates in a cell culture model of murine macrophages

Rey-Jurado, Emma and Tudó, Griselda and Borrell, Sònia and Alcaide, Fernando and Coll, Pere and Español, Montserrat and Martín-Casabona, Núria and Mick, Virginie and Montemayor, Michel and Moure, Raquel and Salvadó, Margarita and Vicente, Eva and González-Martín, Julià. (2011) Impaired fitness of Mycobacterium tuberculosis resistant isolates in a cell culture model of murine macrophages. The journal of antimicrobial chemotherapy, 66 (10). pp. 2277-2280.

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Official URL: http://edoc.unibas.ch/46990/

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Abstract

We analysed the ability of Mycobacterium tuberculosis clinical isolates to penetrate and grow inside murine macrophages as a surrogate of fitness.; Thirty-five drug-resistant and 10 drug-susceptible M. tuberculosis isolates were studied in a murine macrophage model from the J774.2 cell line in a 6 day protocol, performing semi-quantitative counts in Middlebrook 7H11 medium. The mycobacterial penetration index (MPI) after infection and the mycobacterial growth ratio (MGR) inside the macrophages were determined to evaluate the fitness of isolates.; Isolates with the katG S315T mutation and multidrug-resistant (MDR) isolates had a significantly lower MGR compared with drug-susceptible isolates. The MPI of the isolates with the katG S315T mutation showed a significant decrease compared with the MPI of those without this mutation. A trend to significantly lower values was also observed on comparing the MPI of the MDR isolates with that of the drug-susceptible isolates and the isolates resistant to isoniazid.; The isoniazid-resistant and MDR isolates with mutations in the katG gene showed decreased multiplication inside murine macrophages, suggesting a lower fitness of M. tuberculosis with these resistance patterns.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
UniBasel Contributors:Borrell, Sonia
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Academic Press
ISSN:0305-7453
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Mar 2017 08:13
Deposited On:06 Mar 2017 08:13

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