Advancements in anti-tuberculosis drug potentiators: targeting mechanisms of tuberculosis resistance

doi:10.5246/jcps.2024.02.008

Abstract

Abstract:

Tuberculosis (TB) constitutes a formidable global health challenge, exacerbated by the rise of multidrug-resistant TB (MDR-TB) strains. The effectiveness of anti-TB drugs has been hindered by this emergence of resistance. To address this, the development of synergistic compounds, informed by drug resistance mechanisms, holds promise for mitigating resistance emergence and shortening treatment durations. This review focuses on the amalgamation of anti-TB drugs with potentiators targeting the cell wall, efflux pump, and β-lactamase. Our aim is to offer insights that guide the future development of novel potentiators with enhanced efficacy and reduced toxicity.

Key words: Tuberculosis, Drug-resistant strains, Anti-tuberculosis drug potentiators

Supporting:

Jianhui Yang, Xiao Wang, Jinbo Zhang, Yishuang Liu. Advancements in anti-tuberculosis drug potentiators: targeting mechanisms of tuberculosis resistance[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(2): 89-97.

Figures/Tables 3

References 30

[1]	World Health Organization. Global Tuberculosis Report 2022. Geneva: World Health Organization, 2022. This article can be found online at https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022.
[2]	Andres, S.; Merker, M.; Heyckendorf, J.; Kalsdorf, B.; Rumetshofer, R.; Indra, A.; Hofmann-Thiel, S.; Hoffmann, H.; Lange, C.; Niemann, S.; Maurer, F.P. Bedaquiline-resistant tuberculosis: dark clouds on the horizon. Am. J. Respir. Crit. Care Med. 2020, 201, 1564–1568.
[3]	Nimmo, C.; Millard, J.; Brien, K.; Moodley, S.; van Dorp, L.; Lutchminarain, K.; Wolf, A.; Grant, A.D.; Balloux, F.; Pym, A.S.; Padayatchi, N.; O'Donnell, M. Bedaquiline resistance in drug-resistant tuberculosis HIV co-infected patients. Eur. Respir. J. 2020, 55, 1902383.
[4]	Polsfuss, S.; Hofmann-Thiel, S.; Merker, M.; Krieger, D.; Niemann, S.; Rüssmann, H.; Schönfeld, N.; Hoffmann, H.; Kranzer, K. Emergence of low-level delamanid and bedaquiline resistance during extremely drug-resistant tuberculosis treatment. Clin. Infect. Dis. 2019, 69, 1229–1231.
[5]	Singh, R.; Dwivedi, S.P.; Gaharwar, U.S.; Meena, R.; Rajamani, P.; Prasad, T. Recent updates on drug resistance in Mycobacterium tuberculosis. J. Appl. Microbiol. 2020, 128, 1547–1567.
[6]	Pushkaran, A.C.; Vinod, V.; Vanuopadath, M.; Nair, S.S.; Nair, S.V.; Vasudevan, A.K.; Biswas, R.; Mohan, C.G. Combination of repurposed drug diosmin with amoxicillin-clavulanic acid causes synergistic inhibition of mycobacterial growth. Sci. Rep. 2019, 9, 6800.
[7]	Nawaz, N.; Wen, S.; Wang, F.H.; Nawaz, S.; Raza, J.; Iftikhar, M.; Usman, M. Lysozyme and its application as antibacterial agent in food industry. Molecules. 2022, 27, 6305.
[8]	Aguilar-Pérez, C.; Gracia, B.; Rodrigues, L.; Vitoria, A.; Cebrián, R.; Deboosère, N.; Song, O.R.; Brodin, P.; Maqueda, M.; Aínsa, J.A. Synergy between circular bacteriocin AS-48 and ethambutol against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 2018, 62, e00359–18.
[9]	Song, L.L.; Wu, X.Q. Development of efflux pump inhibitors in antituberculosis therapy. Int. J. Antimicrob. Agents. 2016, 47, 421–429.
[10]	Pule, C.M.; Sampson, S.L.; Warren, R.M.; Black, P.A.; van Helden, P.D.; Victor, T.C.; Louw, G.E. Efflux pump inhibitors: targeting mycobacterial efflux systems to enhance TB therapy. J. Antimicrob. Chemother. 2016, 71, 17–26.
[11]	Chen, C.; Gardete, S.; Jansen, R.S.; Shetty, A.; Dick, T.; Rhee, K.Y.; Dartois, V. Verapamil targets membrane energetics in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 2018, 62, e02107–e02117.
[12]	Adams, K.N.; Szumowski, J.D.; Ramakrishnan, L. Verapamil, and its metabolite norverapamil, inhibit macrophage-induced, bacterial efflux pump-mediated tolerance to multiple anti-tubercular drugs. J. Infect. Dis. 2014, 210, 456–466.
[13]	de Souza, J.V.P.; Murase, L.S.; Caleffi-Ferracioli, K.R.; Palomo, C.T.; de Lima Scodro, R.B.; Siqueira, V.L.D.; Pavan, F.R.; Cardoso, R.F. Isoniazid and verapamil modulatory activity and efflux pump gene expression in Mycobacterium tuberculosis. Int. J. Tuberc. Lung Dis. 2020, 24, 591–596.
[14]	Valıyeva, G.; Durupınar, B.; Coban, A.Y. Efflux pump effects on Mycobacterium tuberculosis drug resistance. J. Chemother. 2023, 35, 601–609.
[15]	Singh, M.; Jadaun, G.P.S.; Ramdas, Srivastava, K.; Chauhan, V.; Mishra, R.; Gupta, K.; Nair, S.; Chauhan, D.S.; Sharma, V.D.; Venkatesan, K.; Katoch, V.M. Effect of efflux pump inhibitors on drug susceptibility of ofloxacin resistant Mycobacterium tuberculosis isolates. Indian J. Med. Res. 2011, 133, 535–540.
[16]	Jain, A.; Jaiswal, I.; Verma, S.K.; Singh, P.; Kant, S.; Singh, M. Effect of efflux pump inhibitors on the susceptibility of Mycobacterium tuberculosis to isoniazid. Lung India. 2017, 34, 499–505.
[17]	Hegeto, L.A.; Caleffi-Ferracioli, K.R.; Nakamura-Vasconcelos, S.S.; de Almeida, A.L.; Baldin, V.P.; Nakamura, C.V.; Siqueira, V.L.D.; Scodro, R.B.L.; Cardoso, R.F. In vitro combinatory activity of piperine and anti-tuberculosis drugs in Mycobacterium tuberculosis. Tuberculosis. 2018, 111, 35–40.
[18]	Lentz, F.; Reiling, N.; Spengler, G.; Kincses, A.; Csonka, A.; Molnár, J.; Hilgeroth, A. Dually acting nonclassical 1,4-dihydropyridines promote the anti-tuberculosis (Tb) activities of clofazimine. Molecules. 2019, 24, 2873.
[19]	Halicki, P.C.B.; Vianna, J.S.; Zanatta, N.; de Andrade, V.P.; de Oliveira, M.; Mateus, M.; da Silva, M.V.; Rodrigues, V.; Ramos, D.F.; Almeida da Silva, P.E. 2, 2, 2-trifluoro-1-(1, 4, 5, 6-tetrahydropyridin-3-yl)ethanone derivative as efflux pump inhibitor in Mycobacterium tuberculosis. Bioorg. Med. Chem. Lett. 2021, 42, 128088.
[20]	Kumar, M.; Singh, K.; Naran, K.; Hamzabegovic, F.; Hoft, D.F.; Warner, D.F.; Ruminski, P.; Abate, G.; Chibale, K. Design, synthesis, and evaluation of novel hybrid efflux pump inhibitors for use against Mycobacterium tuberculosis. ACS Infect. Dis. 2016, 2, 714–725.
[21]	Xiao, C.L. Establishment and application of the screening model of the Mycobacterium tuberculosis β-lactamase BlaC inhibitors. J. Chin. Pharm. Sci. 2016, 25, 189–195.
[22]	Flores Anthony, R.; Parsons Linda, M.; Pavelka Martin, S. Genetic analysis of the beta-lactamases of Mycobacterium tuberculosis and Mycobacterium smegmatis and susceptibility to beta-lactam antibiotics. Microbiol. Read. Engl. 2005, 151, 521–532.
[23]	Hugonnet, J.E.; Tremblay, L.W.; Boshoff, H.I.; Barry, C.E.; Blanchard, J.S. Meropenem-clavulanate is effective against extensively drug-resistant Mycobacterium tuberculosis. Science. 2009, 323, 1215–1218.
[24]	Han, J.X; Liu, Y.S.; Xiao, C.L. Research progress of β-lactamase inhibitors. Chin. J. Antibio. 2019, 44, 647–653.
[25]	Payen, M.C.; Muylle, I.; Vandenberg, O.; Mathys, V.; Delforge, M.; Van den Wijngaert, S.; Clumeck, N.; De Wit, S. Meropenem-clavulanate for drug-resistant tuberculosis: a follow-up of relapse-free cases. Int. J. Tuberc. Lung Dis. 2018, 22, 34–39.
[26]	Li, F.; Wang, R.B.; Xiao, T.Y.; Liu, H.; Jiang, Y.; Wan, K.L. Sensitivity analysis of Mycobacterium tuberculosis to β-lactamase inhibitors with tebipenem. Dis. Surveil. 2018, 33, 241–245.
[27]	Shi, J.; Zheng, D.W.; Ma, X.G.; Su, R.Y.; Zhu, Y.K.; Wang, S.H.; Chang, W.J.; Sun, G.Q.; Sun, D.Y. In vitro activity of β-lactamase inhibitors avibanvctam and relebactam in combination with β-lactams against multidrug-resistant Mycobacterium tuberculosis and mutations of resistance genes. Chin. J. Tuberc. Respir. Dis. 2023, 46, 797–805.
[28]	Yan, F.; He, S.G.; Han, X.Y.; Wang, J.Y.; Tian, X.G.; Wang, C.; James, T.D.; Cui, J.N.; Ma, X.C.; Feng, L. High-throughput fluorescent screening of β-lactamase inhibitors to improve antibiotic treatment strategies for tuberculosis. Biosens. Bioelectron. 2022, 216, 114606.
[29]	Jeon, A.B.; Obregón-Henao, A.; Ackart, D.F.; Podell, B.K.; Belardinelli, J.M.; Jackson, M.; Nguyen, T.V.; Blackledge, M.S.; Melander, R.J.; Melander, C.; Johnson, B.K.; Abramovitch, R.B.; Basaraba, R.J. 2-Aminoimidazoles potentiate β-lactam antimicrobial activity against Mycobacterium tuberculosis by reducing β-lactamase secretion and increasing cell envelope permeability. PLoS One. 2017, 12, e0180925.
[30]	Xiao, S.Q.; Guo, H.D.; Weiner, W.S.; Maddox, C.; Mao, C.H.; Gunosewoyo, H.; Pelly, S.; White, E.L.; Rasmussen, L.; Schoenen, F.J.; Aubé, J.; Bishai, W.R.; Lun, S.C. Revisiting the β-lactams for tuberculosis therapy with a compound-compound synthetic lethality approach. Antimicrob. Agents Chemother. 2019, 63, e01319–19.