Skip to content

Research at St Andrews

HspX knock-out in Mycobacterium tuberculosis leads to shorter antibiotic treatment and lower relapse rate in a mouse model - A potential novel therapeutic target

Research output: Research - peer-reviewArticle

DOI

Author(s)

Yanmin Hu, Alexander Liu, Maria C. Menendez, Maria J. Garcia, Katarina Oravcova, Stephen H. Gillespie, Gerry R. Davies, Denis A. Mitchison, Anthony R. M. Coates

School/Research organisations

Abstract

Effective global tuberculosis control is hindered by the need for prolonged chemotherapy which leads to poor patient compliance. Therefore novel drug targets that shorten the duration of chemotherapy and reduce disease relapse rates are highly desirable. We have previously shown that HspX, an alpha-crystallin-like protein, is associated with growth suppression of Mycobacterium tuberculosis in mouse models. We determined to evaluate hspX as a novel target for controlling M. tuberculosis growth in combination with traditional antibiotic therapy in the Cornell mouse model. The hspX deletion mutant (Δ hspX) was used as a model of potential hspX inhibition. Normal BALB/c mice were infected with ΔhspX or the wild type (WT) strain. Three weeks after infection, the mice were treated with rifampicin, isoniazid and pyrazinamide for 14 weeks followed by 8 weeks of hydrocortisone. The effect of chemotherapy was measured by organ bacterial counts and the relapse rate. Antibiotic treatment of mice infected with ΔhspX resulted in faster visceral clearance; organs were disease free 8 weeks post-treatment for ΔhspX infection compared to 14 weeks for the WT strain. Disease relapse rate was significantly lower in ΔhspX infection (60.7%) compared to WT infection (92.6%). HspX may be a promising therapeutic target in combination with traditional antibiotic therapy to shorten the length of treatment and reduce disease relapse.

Close

Details

Original languageEnglish
Pages (from-to)31-36
Number of pages6
JournalTuberculosis
Volume95
Issue number1
Early online date20 Nov 2014
DOIs
StatePublished - Jan 2015

    Research areas

  • Mycobacterium tuberculosis, hspX knock-out mutant, Treatment, Mouse model, Microbial enumeration technique, Alpha-crystallin, Statrionary-phase, Gene-expression, Dormancy, Pyrazinamide, Infection, Transcription, Rifampin, Tissues

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. The impact of repeated NALC/NaOH- decontamination on the performance of Xpert MTB/RIF assay

    Rachow, A., Saathoff, E., Mtafya, B., Mapamba, D., Mangu, C., Rojas-Ponce, G., Ntinginya, N. E., Boeree, M., Heinrich, N., Gillespie, S. H., Hoelscher, M. & on behalf of the PanACEA-Consortium 4 Apr 2018 In : Tuberculosis. In press

    Research output: Research - peer-reviewArticle

  2. A population pharmacokinetic model incorporating saturable pharmacokinetics and autoinduction for high rifampicin doses

    Svensson, R. J., Aarnoutse, R. E., Diacon, A. H., Dawson, R., Gillespie, S. H., Boeree, M. J. & Simonsson, U. S. H. Apr 2018 In : Clinical Pharmacology & Therapeutics. 103, p. 674-683 10 p.

    Research output: Research - peer-reviewArticle

  3. Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis

    Fregonese, F. , Ahuja, S. D. , Akkerman, O. W. , Arakaki-Sanchez, D. , Ayakaka, I. , Baghaei, P. , Bang, D. , Bastos, M. , Benedetti, A. , Bonnet, M. , Cattamanchi, A. , Cegielski, P. , Chien, J-Y. , Cox, H. , Dedicoat, M. , Erkens, C. , Escalante, P. , Falzon, D. , Garcia-Prats, A. J. , Gegia, M. & 38 others Gillespie, S. H., Glynn, J. R., Goldberg, S., Griffith, D., Jacobson, K. R., Johnston, J. C., Jones-López, E. C., Khan, A., Koh, W-J., Kritski, A., Lan, Z. Y., Lee, J. H., Li, P. Z., Maciel, E. L., Galliez, R. M., Merle, C. S. C., Munang, M., Narendran, G., Nguyen, V. N., Nunn, A., Ohkado, A., Park, J. S., Phillips, P. P. J., Ponnuraja, C., Reves, R., Romanowski, K., Seung, K., Schaaf, H. S., Skrahina, A., Soolingen, D. V., Tabarsi, P., Trajman, A., Trieu, L., Banurekha, V. V., Viiklepp, P., Wang, J-Y., Yoshiyama, T. & Menzies, D. Apr 2018 In : The Lancet Respiratory Medicine. 6, 4, p. 265-275 11 p.

    Research output: Research - peer-reviewArticle

  4. Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study

    Tweed, C. D., Wills, G. H., Crook, A. M., Dawson, R., Diacon, A. H., Louw, C. E., McHugh, T. D., Mendel, C., Meredith, S., Mohapi, L., Murphy, M. E., Murray, S., Murthy, S., Nunn, A. J., Phillips, P. P. J., Singh, K., Spigelman, M. & Gillespie, S. H. 28 Mar 2018 In : BMC Medicine. 16, 10 p., 46

    Research output: Research - peer-reviewArticle

Related by journal

  1. The impact of repeated NALC/NaOH- decontamination on the performance of Xpert MTB/RIF assay

    Rachow, A., Saathoff, E., Mtafya, B., Mapamba, D., Mangu, C., Rojas-Ponce, G., Ntinginya, N. E., Boeree, M., Heinrich, N., Gillespie, S. H., Hoelscher, M. & on behalf of the PanACEA-Consortium 4 Apr 2018 In : Tuberculosis. In press

    Research output: Research - peer-reviewArticle

  2. Defining dormancy in mycobacterial disease

    Lipworth, S., Hammond, R. J. H., Baron, V. O., Hu, Y., Coates, A. & Gillespie, S. H. Jul 2016 In : Tuberculosis. 99, p. 131-142 12 p.

    Research output: Research - peer-reviewArticle

  3. Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB

    Barr, D. A., Kamdolozi, M., Nishihara, Y., Ndhlovu, V., Khonga, M., Davies, G. R. & Sloan, D. J. May 2016 In : Tuberculosis. 98, p. 110-115 6 p.

    Research output: Research - peer-reviewArticle

  4. Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis

    Mzinza, D. T., Sloan, D. J., Jambo, K. C., Shani, D., Kamdolozi, M., Wilkinson, K. A., Wilkinson, R. J., Davies, G. R., Heyderman, R. S. & Mwandumba, H. C. 1 Jul 2015 In : Tuberculosis. 95, 4, p. 463-469 7 p., 1343

    Research output: Research - peer-reviewArticle

ID: 163387425