816
Views
30
CrossRef citations to date
0
Altmetric
Review

In vitro drug discovery models for Mycobacterium tuberculosis relevant for host infection

ORCID Icon
Pages 349-358 | Received 20 Aug 2019, Accepted 18 Dec 2019, Published online: 03 Jan 2020

References

  • WHO. Guidelines for treatment of tuberculosis. 2010. [cited 2019 Dec 31]. Available from: http://www.who.int/tb/publications/2010/9789241547833/en/
  • Gordon SV, Parish T. Microbe profile: Mycobacterium tuberculosis: humanity’s deadly microbial foe. Microbiology. 2018;164(4):437–439.
  • WHO. Global tuberculosis report 2018. 2018. [cited 2019 Dec 31]. Available from: http://www.who.int/tb/publications/global_report/en/
  • Ryan NJ, Lo JH. Delamanid: first global approval. Drugs. 2014 Jun;74(9):1041–1045.
  • FDA. 2012 [cited 2019 Aug 15]. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-resistant-forms-tuberculosis-affects-lungs
  • TB Alliance. 2019 [cited 2019 Aug 15]. Available from: https://www.tballiance.org/news/fda-approves-new-treatment-highly-drug-resistant-forms-tuberculosis
  • Treatment Action Group. Progress in the fight for better treatment, prevention, a vaccine, and a cure for HIV, tuberculosis, and hepatitis C virus. 2018.
  • Queval CJ, Brosch R, Simeone R. The macrophage: a disputed fortress in the battle against Mycobacterium tuberculosis. Front Microbiol. 2017;8:2284.
  • Russell DG, Barry CE 3rd, Flynn JL. Tuberculosis: what we don’t know can, and does, hurt us. Science (New York, NY). 2010 May 14;328(5980):852–856.
  • Houben RM, Dodd PJ. The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med. 2016 Oct;13(10):e1002152.
  • Mandal S, Njikan S, Kumar A, et al. The relevance of persisters in tuberculosis drug discovery. Microbiology. 2019 May;165(5):492–499.
  • Kumar A, Chettiar S, Parish T. Current challenges in drug discovery for tuberculosis. Expert Opin Drug Discov. 2017 Jan;12(1):1–4.
  • Zuniga E, Early J, Parish T. The future for early stage tuberculosis drug discovery. Future Microbiol. 2015;10:217–229.
  • Boshoff HI, Barry CE 3rd. Tuberculosis - metabolism and respiration in the absence of growth. Nature Rev Microbiol. 2005 Jan;3(1):70–80.
  • Ortalo-Magne A, Lemassu A, Laneelle MA, et al. Identification of the surface-exposed lipids on the cell envelopes of Mycobacterium tuberculosis and other mycobacterial species. J Bacteriol. 1996 Jan;178(2):456–461.
  • Pethe K, Sequeira PC, Agarwalla S, et al. A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy. Nat Commun. 2010 Aug 24;1:57.
  • Ollinger J, Kumar A, Roberts DM, et al. A high-throughput whole cell screen to identify inhibitors of Mycobacterium tuberculosis. PloS One. 2019;14(1):e0205479.
  • Ananthan S, F ER, G RC, et al. High-throughput screening for inhibitors of Mycobacterium tuberculosis H37Rv. Tuberculosis. 2008;89(5):334–353.
  • Munoz-Elias EJ, McKinney JD. Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Nat Med. 2005 Jun;11(6):638–644.
  • Pandey AK, Sassetti CM. Mycobacterial persistence requires the utilization of host cholesterol. Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4376–4380.
  • Marrero J, Trujillo C, Rhee KY, et al. Glucose phosphorylation is required for Mycobacterium tuberculosis persistence in mice. PLoS Pathog. 2013 Jan;9(1):e1003116.
  • Munoz-Elias EJ, Upton AM, Cherian J, et al. Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. Mol Microbiol. 2006 Jun;60(5):1109–1122.
  • Munoz-Elias EJ, McKinney JD. Carbon metabolism of intracellular bacteria. Cell Microbiol. 2006 Jan;8(1):10–22.
  • Marrero J, Rhee KY, Schnappinger D, et al. Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9819–9824.
  • Early JV, Casey A, Martinez-Grau MA, et al. Oxadiazoles have butyrate-specific conditional activity against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2016 Jun;60(6):3608–3616.
  • VanderVen BC, Fahey RJ, Lee W, et al. Novel inhibitors of cholesterol degradation in Mycobacterium tuberculosis reveal how the bacterium’s metabolism is constrained by the intracellular environment. PLoS Pathog. 2015 Feb;11(2):e1004679.
  • Gold B, Nathan C. Targeting phenotypically tolerant Mycobacterium tuberculosis. Microbiol Spectr. 2017 Jan;5(1). doi:10.1128/microbiolspec.TBTB2-0031-2016.
  • Betts JC, Lukey PT, Robb LC, et al. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol. 2002 Feb;43(3):717–731.
  • Grant SS, Kawate T, Nag PP, et al. Identification of novel inhibitors of nonreplicating Mycobacterium tuberculosis using a carbon starvation model. ACS Chem Biol. 2013 Oct 18;8(10):2224–2234.
  • Via LE, Lin PL, Ray SM, et al. Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates. Infect Immun. 2008 Jun;76(6):2333–2340.
  • Heng Y, Seah PG, Siew JY, et al. Mycobacterium tuberculosis infection induces hypoxic lung lesions in the rat. Tuberculosis (Edinb). 2011 Jul;91(4):339–341.
  • Datta M, Via LE, Chen W, et al. Mathematical model of oxygen transport in tuberculosis granulomas. Ann Biomed Eng. 2016 Apr;44(4):863–872.
  • Cho SH, Warit S, Wan B, et al. Low-oxygen-recovery assay for high-throughput screening of compounds against nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2007 Apr;51(4):1380–1385.
  • Sohaskey CD, Voskuil MI. In vitro models that utilize hypoxia to induce non-replicating persistence in Mycobacteria. Methods Mol Biol. 2015;1285:201–213.
  • Wayne LG. In vitro model of hypoxically induced nonreplicating persistence of Mycobacterium tuberculosis. Methods Mol Med. 2001;54:247–269.
  • Wayne LG, Hayes LG. An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect Immun. 1996 Jun;64(6):2062–2069.
  • Wayne LG, Sohaskey CD. Nonreplicating persistence of mycobacterium tuberculosis. Annu Rev Microbiol. 2001;55:139–163.
  • Muttucumaru DG, Roberts G, Hinds J, et al. Gene expression profile of Mycobacterium tuberculosis in a non-replicating state. Tuberculosis (Edinb). 2004;84(3–4):239–246.
  • Yeware A, Sarkar D. Novel red fluorescence protein based microplate assay for drug screening against dormant Mycobacterium tuberculosis by using paraffin. Tuberculosis (Edinb). 2018 May;110:15–19.
  • Aguilar-Ayala DA, Cnockaert M, Vandamme P, et al. Antimicrobial activity against Mycobacterium tuberculosis under in vitro lipid-rich dormancy conditions. J Med Microbiol. 2018 Mar;67(3):282–285.
  • Early JV, Mullen S, Parish T. A rapid method to determine the bactericidal activity of compounds against non-replicating Mycobacterium tuberculosis at low pH. bioRxiv. 2019;578195. doi: 10.1101/578195.
  • Darby CM, Ingolfsson HI, Jiang X, et al. Whole cell screen for inhibitors of pH homeostasis in Mycobacterium tuberculosis. PloS One. 2013;8(7):e68942.
  • Early J, Ollinger J, Darby C, et al. Identification of compounds with pH-dependent bactericidal activity against Mycobacterium tuberculosis. ACS Infect Dis. 2019 Feb 8;5(2):272–280.
  • Zhang M, Sala C, Hartkoorn RC, et al. Streptomycin-starved Mycobacterium tuberculosis 18b, a drug discovery tool for latent tuberculosis. Antimicrob Agents Chemother. 2012 Nov;56(11):5782–5789.
  • Vocat A, Hartkoorn RC, Lechartier B, et al. Bioluminescence for assessing drug potency against nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015 Jul;59(7):4012–4019.
  • Campos-Neto A. Mycobacterium tuberculosis strain 18b, a useful non-virulent streptomycin dependent mutant to study latent tuberculosis as well as for in vivo and in vitro testing of anti-tuberculosis drugs. Tuberculosis (Edinb). 2016 Jul;99:54–55.
  • Sala C, Dhar N, Hartkoorn RC, et al. Simple model for testing drugs against nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2010 Oct;54(10):4150–4158.
  • Deb C, Lee CM, Dubey VS, et al. A novel in vitro multiple-stress dormancy model for Mycobacterium tuberculosis generates a lipid-loaded, drug-tolerant, dormant pathogen. PloS One. 2009;4(6):e6077.
  • Gold B, Warrier T, Nathan C. A multi-stress model for high throughput screening against non-replicating Mycobacterium tuberculosis. Methods Mol Biol. 2015;1285:293–315.
  • Gold B, Roberts J, Ling Y, et al. Visualization of the charcoal agar resazurin assay for semi-quantitative, medium-throughput enumeration of Mycobacteria. J Vis Exp. 2016 Dec 14;(118):e54690.
  • Gold B, Roberts J, Ling Y, et al. Rapid, semiquantitative assay to discriminate among compounds with activity against replicating or nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015 Oct;59(10):6521–6538.
  • Bassett IM, Lun S, Bishai WR, et al. Detection of inhibitors of phenotypically drug-tolerant Mycobacterium tuberculosis using an in vitro bactericidal screen. J Microbiol. 2013 Oct;51(5):651–658.
  • Hu Y, Coates ARM, Mitchison DA. Sterilizing activities of fluoroquinolones against rifampin-tolerant populations of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2003;47(2):653–657.
  • Huang L, Nazarova EV, Russell DG. Mycobacterium tuberculosis: bacterial Fitness within the host macrophage. Microbiol Spectr. 2019 Mar;7(2). doi: 10.1128/microbiolspec.BAI-0001-2019.
  • Manning AJ, Ovechkina Y, McGillivray A, et al. A high content microscopy assay to determine drug activity against intracellular Mycobacterium tuberculosis. Methods. 2017 Aug 15;127:3–11. doi: 10.1016/j.ymeth.2017.03.022.
  • Christophe T, Jackson M, Jeon HK, et al. High content screening identifies decaprenyl-phosphoribose 2ʹ epimerase as a target for intracellular antimycobacterial inhibitors. PLoS Pathog. 2009 Oct;5(10):e1000645.
  • Stanley SA, Grant SS, Kawate T, et al. Identification of novel inhibitors of M. tuberculosis growth using whole cell based high-throughput screening. ACS Chem Biol. 2012 Aug 17;7(8):1377–1384.
  • Sorrentino F, Gonzalez Del Rio R, Zheng X, et al. Development of an intracellular screen for new compounds able to inhibit Mycobacterium tuberculosis growth in human macrophages. Antimicrob Agents Chemother. 2016 Jan;60(1):640–645.
  • Zheng X, Av-Gay Y. System for efficacy and cytotoxicity screening of inhibitors targeting intracellular Mycobacterium tuberculosis. J Vis Exp.2017 Apr 5; (122). doi: 10.3791/55273.
  • Larsson MC, Lerm M, Angeby K, et al. A luciferase-based assay for rapid assessment of drug activity against Mycobacterium tuberculosis including monitoring of macrophage viability. J Microbiol Methods. 2014 Nov;106:146–150.
  • Queval CJ, Song OR, Delorme V, et al. A microscopic phenotypic assay for the quantification of intracellular mycobacteria adapted for high-throughput/high-content screening. J Vis Exp. 2014 Jan 17;(83):e51114. doi:10.3791/51114.
  • Crouser ED, White P, Caceres EG, et al. A novel in vitro human granuloma model of sarcoidosis and latent tuberculosis infection. Am J Respir Cell Mol Biol. 2017 Oct;57(4):487–498.
  • Tanner L, Denti P, Wiesner L, et al. Drug permeation and metabolism in Mycobacterium tuberculosis: prioritising local exposure as essential criterion in new TB drug development. IUBMB Life. 2018 Sep;70(9):926–937.
  • Sarathy JP, Zuccotto F, Hsinpin H, et al. Prediction of drug penetration in tuberculosis lesions. ACS Infect Dis. 2016 Aug 12;2(8):552–563.
  • Strydom N, Gupta SV, Fox WS, et al. Tuberculosis drugs’ distribution and emergence of resistance in patient’s lung lesions: A mechanistic model and tool for regimen and dose optimization. PLoS Med. 2019 Apr;16(4):e1002773.
  • Sarathy J, Blanc L, Alvarez-Cabrera N, et al. Fluoroquinolone efficacy against tuberculosis is driven by penetration into lesions and activity against Resident bacterial populations. Antimicrob Agents Chemother. 2019 May;63(5):e02516-18. doi: 10.1128/AAC.02516-18.
  • Blanc L, Daudelin IB, Podell BK, et al. High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types. eLife. 2018 Nov 14;7:e41115. doi: 10.7554/eLife.41115.
  • Dick T, Dartois V. TB drug susceptibility is more than MIC. Nat Microbiol. 2018 Sep;3(9):971–972.
  • Zimmerman M, Blanc L, Chen PY, et al. Spatial quantification of drugs in pulmonary tuberculosis lesions by laser capture microdissection liquid chromatography mass spectrometry (LCM-LC/MS). J Vis Exp.2018 Apr 18; (134).
  • Blanc L, Lenaerts A, Dartois V, et al. Visualization of Mycobacterial biomarkers and tuberculosis drugs in infected tissue by MALDI-MS imaging. Anal Chem. 2018 May 15;90(10):6275–6282.
  • Sarathy JP, Via LE, Weiner D, et al. Extreme drug tolerance of Mycobacterium tuberculosis in caseum. Antimicrob Agents Chemother. 2018 Jan; 25;62(2):e02266-17. doi: 10.1128/AAC.02266-17.
  • Sarathy JP, Liang HH, Weiner D, et al. An in  vitro caseum binding assay that predicts drug penetration in tuberculosis lesions. J Vis Exp. 2017 May 8:(123). doi: 10.3791/55559
  • Elkington P, Lerm M, Kapoor N, et al. In vitro granuloma models of tuberculosis: potential and challenges. J Infect Dis. 2019 May 24;219(12):1858–1866.
  • Silva-Miranda M, Ekaza E, Breiman A, et al. High-content screening technology combined with a human granuloma model as a new approach to evaluate the activities of drugs against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015 Jan;59(1):693–697.
  • Huang L, Kushner NL, Theriault ME, et al. The deconstructed granuloma: a complex high-throughput drug screening platform for the discovery of host-directed therapeutics against tuberculosis. Front Cell Infect Microbiol. 2018;8:275.
  • Cronan MR, Matty MA, Rosenberg AF, et al. An explant technique for high-resolution imaging and manipulation of mycobacterial granulomas. Nat Methods. 2018 Dec;15(12):1098–1107.
  • Braian C, Svensson M, Brighenti S, et al. A 3D human lung tissue model for functional studies on Mycobacterium tuberculosis infection. J Vis Exp.2015 Oct 5; (104). doi: 10.3791/53084.
  • Takaki K, Cosma CL, Troll MA, et al. An in vivo platform for rapid high-throughput antitubercular drug discovery. Cell Rep. 2012 Jul 26;2(1):175–184.
  • Spaink HP, Cui C, Wiweger MI, et al. Robotic injection of zebrafish embryos for high-throughput screening in disease models. Methods. 2013 Aug 15;62(3):246–254.
  • Carvalho R, de Sonneville J, Stockhammer OW, et al. A high-throughput screen for tuberculosis progression. PloS One. 2011 Feb 16;6(2):e16779.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.