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: Contribution to journalArticle



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


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.



Original languageEnglish
Pages (from-to)31-36
Number of pages6
Issue number1
Early online date20 Nov 2014
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. Pseudomonas aeruginosa intensive care unit outbreak: winnowing of transmissions with molecular and genomic typing

    Parcell, B. J., Oravcova, K., Pinheiro, M., Holden, M. T. G., Phillips, G., Turton, J. F. & Gillespie, S. H. 8 Dec 2017 In : Journal of Hospital Infection. In press

    Research output: Contribution to journalArticle

  2. Project Sanitarium: playing tuberculosis to its end game

    Donald, I., Meyer, K., Brengman, J., Gillespie, S. H. & Bowness, R. Dec 2017 In : Journal of Computing in Higher Education. 29, 3, p. 599-617 19 p.

    Research output: Contribution to journalArticle

  3. A comparison of liquid and solid culture for determining relapse and durable cure in phase III TB trials for new regimens

    Phillips, P. P. J., Mendel, C. M., Nunn, A. J., McHugh, T. D., Crook, A. M., Hunt, R., Bateson, A. & Gillespie, S. H. 24 Nov 2017 In : BMC Medicine. 15, 9 p., 207

    Research output: Contribution to journalArticle

  4. Pharmacokinetics, tolerability, and bacteriological response of rifampin administered at 600, 900, and 1,200 milligrams daily in patients with pulmonary tuberculosis

    Aarnoutse, R. E., Kibiki, G. S., Reither, K., Semvua, H. H., Haraka, F., Mtabho, C. M., Mpagama, S. G., van den Boogaard, J., Sumari-de Boer, I. M., Magis-Escurra, C., Wattenberg, M., Logger, J. G. M., te Brake, L. H. M., Hoelscher, M., Gillespie, S. H., Colbers, A., Phillips, P. P. J., Plemper van Balen, G., Boeree, M. J. & PanACEA Consortium 1 Nov 2017 In : Antimicrobial Agents and Chemotherapy. 61, 11, e01054-17

    Research output: Contribution to journalArticle

  5. Spot sputum samples are at least as good as early morning samples for identifying Mycobacterium tuberculosis

    Murphy, M. E., Phillips, P. P. J., Mendel, C. M., Bongard, E., Bateson, A. L. C., Hunt, R., Murthy, S., Singh, K. P., Brown, M., Crook, A. M., Nunn, A. J., Meredith, S. K., Lipman, M., McHugh, T. D., Gillespie, S. H. & on behalf of the REMoxTB Consortium 27 Oct 2017 In : BMC Medicine. 15, 10 p., 192

    Research output: Contribution to journalArticle

Related by journal

  1. 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: Contribution to journalArticle

  2. 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: Contribution to journalArticle

  3. 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: Contribution to journalArticle

  4. Resuscitation-promoting factors are expressed in Mycobacterium tuberculosis-infected human tissue

    Davies, A. P., Dhillon, A. P., Young, M., Henderson, B., McHugh, T. D. & Gillespie, S. H. Sep 2008 In : Tuberculosis. 88, 5, p. 462-468 7 p.

    Research output: Contribution to journalArticle

ID: 163387425