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

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
Publication statusPublished - 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. Mimicking in-vivo exposures to drug combinations in-vitro: anti-tuberculosis drugs in lung lesions and the hollow fiber model of infection

    Kloprogge, F., Hammond, R., Kipper, K., Gillespie, S. H. & Della Pasqua, O., 13 Sep 2019, In : Scientific Reports. 9, 8 p., 13228.

    Research output: Contribution to journalArticle

  2. A tuberculosis molecular bacterial load assay (TB-MBLA)

    Sabiiti, W., Mtafya, B. A., Alferes De Lima, D., Dombay, E., Baron, V. O., Azam, K., Orascova, K., Sloan, D. J. & Gillespie, S. H., 6 Sep 2019, (Accepted/In press) In : Journal of Visualized Experiments.

    Research output: Contribution to journalArticle

  3. Can phenotypic data complement our understanding of antimycobacterial effects for drug combinations?

    Kloprogge, F., Hammond, R., Copas, A., Gillespie, S. H. & Della Pasqua, O., 25 Aug 2019, In : Journal of Antimicrobial Chemotherapy. Advance article, 7 p.

    Research output: Contribution to journalArticle

  4. Toxicity related to standard TB therapy for pulmonary tuberculosis and treatment outcomes in the REMoxTB study according to HIV status

    Tweed, C. D., Crook, A. M., Dawson, R., Diacon, A. H., McHugh, T. D., Mendel, C. M., Meredith, S. K., Mohapi, L., Murphy, M. E., Nunn, A. J., Phillips, P. P. J., Singh, K. P., Spigelman, M. & Gillespie, S. H., 14 Aug 2019, In : BMC Pulmonary Medicine. 19, 9 p., 152.

    Research output: Contribution to journalArticle

  5. Model-based relationship between the molecular bacterial load assay and time-to-positivity in liquid culture

    Svensson, R. J., Sabiiti, W., Kibiki, G. S., Ntinginya, N. E., Bhatt, N., Davies, G., Gillespie, S. H. & Simonsson, U. S. H., 29 Jul 2019, In : Antimicrobial Agents and Chemotherapy. Early

    Research output: Contribution to journalArticle

Related by journal

  1. Centrifugation and decontamination procedures selectively impair recovery of important populations in Mycobacterium smegmatis

    Kennedy, J. A., Baron, V. O., Hammond, R. J. H., Sloan, D. J. & Gillespie, S. H., 1 Aug 2018, In : Tuberculosis.

    Research output: Contribution to journalArticle

  2. 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. & PanACEA Consortium, 4 Apr 2018, In : Tuberculosis. In press

    Research output: Contribution to journalArticle

  3. 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

  4. 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

ID: 163387425