Research progress for delamanid resistance mechanism of Mycobacterium tuberculosis

doi:10.3969/j.issn.1000-6621.2020.11.017

Abstract

Abstract:

At present, tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is still the leading cause of death for infectious diseases worldwide. The spread of drug-resistant strains has caused great difficulties in the treatment of TB. Delamanid (Dlm), a new anti-TB drug, is effective against multi-drug resistant (MDR) or extensively drug-resistant (XDR) tuberculosis. Accurate and timely detection of Dlm-resistant strains can maximize the effectiveness of clinical application for the drug and improve the cure rate of MDR-TB/XDR-TB. The acquired drug resistance in MTB is mainly caused by resistance associated gene mutations. This article reviews the resistance mechanism and resistance associated gene mutations of Dlm, to provide some reference for the early molecular diagnosis of Dlm-resistant strains.

Key words: Mycobacterium tuberculosis, Delamanid, Drug resistance, Molecular mechanisms of pharmacological action, Point mutation, Review literature as topic

LIU Yuan-yuan, CHU Ping, HAN Shu-jing, YANG Hui, LU Jie. Research progress for delamanid resistance mechanism of Mycobacterium tuberculosis[J]. Chinese Journal of Antituberculosis, 2020, 42(11): 1237-1242. doi: 10.3969/j.issn.1000-6621.2020.11.017

Figures/Tables 6

References 28

[1]	World Health Organization. Global tuberculosis report 2019. Geneva:World Health Organization, 2019.
[2]	Matteelli A, Roggi A, Carvalho AC. Extensively drug-resistant tuberculosis: epidemiology and management. Clin Epidemiol, 2014,6:111-118. doi: 10.2147/CLEP.S35839. doi: 10.2147/CLEP.S35839 URL pmid: 24729727
[3]	Orenstein EW, Basu S, Shah NS, et al. Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. Lancet Infect Dis, 2009,9(3):153-161. doi: 10.1016/S1473-3099(09)70041-6. doi: 10.1016/S1473-3099(09)70041-6 URL pmid: 19246019
[4]	Johnston JC, Shahidi NC, Sadatsafavi M, et al. Treatment outcomes of multidrug-resistant tuberculosis: a systematic review and meta-analysis. PLoS One, 2009,4(9):e6914. doi: 10.1371/journal.pone.0006914. doi: 10.1371/journal.pone.0006914 URL pmid: 19742330
[5]	Jacobson KR, Tierney DB, Jeon CY, et al. Treatment outcomes among patients with extensively drug-resistant tuberculosis: systematic review and meta-analysis. Clin Infect Dis, 2010,51(1):6-14. doi: 10.1086/653115. doi: 10.1086/653115 URL pmid: 20504231
[6]	World Health Organization. The Use of Delamanid in the Treatment of Multidrug-Resistant Tuberculosis: Interim Policy Guidance. Geneva:World Health Organization, 2014.
[7]	Liu Y, Matsumoto M, Ishida H, et al. Delamanid: From discovery to its use for pulmonary multidrug-resistant tuberculosis (MDR-TB). Tuberculosis (Edinb), 2018,111:20-30. doi: 10.1016/j.tube.2018.04.008.
[8]	Matsumoto M, Hashizume H, Tomishige T, et al. OPC-67683, a nitro-dihydro-imidazooxazole derivative with promi-sing action against tuberculosis in vitro and in mice. PLoS Med, 2006,3(11):e466. doi: 10.1371/journal.pmed.0030466. doi: 10.1371/journal.pmed.0030466 URL pmid: 17132069
[9]	Yuan Y, Zhu Y, Crane DD, et al. The effect of oxygenated mycolic acid composition on cell wall function and macrophage growth in Mycobacterium tuberculosis. Mol Microbiol, 1998,29(6):1449-1458. doi: 10.1046/j.1365-2958.1998.01026.x. doi: 10.1046/j.1365-2958.1998.01026.x URL pmid: 9781881
[10]	Van den Bossche A, Varet H, Sury A, et al. Transcriptional profiling of a laboratory and clinical Mycobacterium tuberculosis strain suggests respiratory poisoning upon exposure to delamanid. Tuberculosis (Edinb), 2019,117:18-23. doi: 10.1016/j.tube.2019.05.002.
[11]	Barry PJ, O’Connor TM. Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem, 2007,14(18):2000-2008. doi: 10.2174/092986707781368496. doi: 10.2174/092986707781368496 URL pmid: 17691942
[12]	Blair HA, Scott LJ. Delamanid: a review of its use in patients with multidrug-resistant tuberculosis. Drugs, 2015,75(1):91-100. doi: 10.1007/s40265-014-0331-4. doi: 10.1007/s40265-014-0331-4 URL pmid: 25404020
[13]	Bloemberg GV, Keller PM, Stucki D, et al. Acquired Resis-tance to Bedaquiline and Delamanid in Therapy for Tuberculosis. N Engl J Med, 2015,373(20):1986-1988. doi: 10.1056/NEJMc1505196. doi: 10.1056/NEJMc1505196 URL pmid: 26559594
[14]	Hoffmann H, Kohl TA, Hofmann-Thiel S, et al. Delamanid and Bedaquiline Resistance in Mycobacterium tuberculosis Ancestral Beijing Genotype Causing Extensively Drug-Resis-tant Tuberculosis in a Tibetan Refugee. Am J Respir Crit Care Med, 2016,193(3):337-340. doi: 10.1164/rccm.201502-0372LE. doi: 10.1164/rccm.201502-0372LE URL pmid: 26829425
[15]	Fujiwara M, Kawasaki M, Hariguchi N, et al. Mechanisms of resistance to delamanid, a drug for Mycobacterium tuberculosis. Tuberculosis (Edinb), 2018,108:186-194. doi: 10.1016/j.tube.2017.12.006.
[16]	Kardan-Yamchi J, Kazemian H, Battaglia S, et al. Whole Genome Sequencing Results Associated with Minimum Inhibitory Concentrations of 14 Anti-Tuberculosis Drugs among Rifampicin-Resistant Isolates of Mycobacterium Tuberculosis from Iran. J Clin Med, 2020,9(2):465. doi: 10.3390/jcm9020465.
[17]	Wen S, Jing W, Zhang T, et al. Comparison of in vitro activity of the nitroimidazoles delamanid and pretomanid against multidrug-resistant and extensively drug-resistant tuberculosis. Eur J Clin Microbiol Infect Dis, 2019,38(7):1293-1296. doi: 10.1007/s10096-019-03551-w. URL pmid: 30953211
[18]	Yang JS, Kim KJ, Choi H, et al. Delamanid, Bedaquiline, and Linezolid Minimum Inhibitory Concentration Distributions and Resistance-related Gene Mutations in Multidrug-resistant and Extensively Drug-resistant Tuberculosis in Korea. Ann Lab Med, 2018,38(6):563-568. doi: 10.3343/alm.2018.38.6.563. doi: 10.3343/alm.2018.38.6.563 URL pmid: 30027700
[19]	Pang Y, Zong Z, Huo F, et al. In Vitro Drug Susceptibility of Bedaquiline, Delamanid, Linezolid, Clofazimine, Moxifloxacin, and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in Beijing, China. Antimicrob Agents Chemother, 2017,61(10):e00900-17. doi: 10.1128/AAC.00900-17. doi: 10.1128/AAC.00900-17 URL pmid: 28739779
[20]	Schena E, Nedialkova L, Borroni E, et al. Delamanid susceptibility testing of Mycobacterium tuberculosis using the resazurin microtitre assay and the BACTEC ^TM MGIT^TM 960 system . J Antimicrob Chemother, 2016,71(6):1532-1539. doi: 10.1093/jac/dkw044. doi: 10.1093/jac/dkw044 URL pmid: 27076101
[21]	Coll F, Phelan J, Hill-Cawthorne GA, et al. Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis. Nat Genet, 2018,50(2):307-316. doi: 10.1038/s41588-017-0029-0. doi: 10.1038/s41588-017-0029-0 URL pmid: 29358649
[22]	Purwantini E, Mukhopadhyay B. Conversion of NO₂ to NO by reduced coenzyme F₄₂₀ protects mycobacteria from nitrosative damage. Proc Natl Acad Sci U S A, 2009,106(15):6333-6338. doi: 10.1073/pnas.0812883106. doi: 10.1073/pnas.0812883106 URL pmid: 19325122
[23]	Griffin JE, Gawronski JD, Dejesus MA, et al. High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. PLoS Pathog, 2011,7(9):e1002251. doi: 10.1371/journal.ppat.1002251. doi: 10.1371/journal.ppat.1002251 URL pmid: 21980284
[24]	Rancoita PMV, Cugnata F, Gibertoni Cruz AL, et al. Validating a 14-Drug Microtiter Plate Containing Bedaquiline and Delamanid for Large-Scale Research Susceptibility Testing of Mycobacterium tuberculosis. Antimicrob Agents Chemother, 2018,62(9):e00344-18. doi: 10.1128/AAC.00344-18. doi: 10.1128/AAC.00344-18 URL pmid: 29941636
[25]	Polsfuss S, Hofmann-Thiel S, Merker M, et al. Emergence of Low-level Delamanid and Bedaquiline Resistance During Extremely Drug-resistant Tuberculosis Treatment. Clin Infect Dis, 2019,69(7):1229-1231. doi: 10.1093/cid/ciz074. doi: 10.1093/cid/ciz074 URL pmid: 30933266
[26]	Ghodousi A, Rizvi AH, Baloch AQ, et al. Acquisition of Cross-Resistance to Bedaquiline and Clofazimine following Treatment for Tuberculosis in Pakistan. Antimicrob Agents Chemother, 2019,63(9):e00915-19. doi: 10.1128/AAC.00915-19. doi: 10.1128/AAC.00915-19 URL pmid: 31262765
[27]	Haver HL, Chua A, Ghode P, et al. Mutations in genes for the F₄₂₀ biosynthetic pathway and a nitroreductase enzyme are the primary resistance determinants in spontaneous in vitro-selected PA-824-resistant mutants of Mycobacterium tuberculosis. Antimicrob Agents Chemother, 2015,59(9):5316-5323. doi: 10.1128/AAC.00308-15. doi: 10.1128/AAC.00308-15 URL pmid: 26100695
[28]	Mukherjee T, Boshoff H. Nitroimidazoles for the treatment of TB: past, present and future. Future Med Chem, 2011,3(11):1427-1454. doi: 10.4155/fmc.11.90. doi: 10.4155/fmc.11.90 URL pmid: 21879846

突变类型	突变位点	MIC值 (mg/L)	菌株(株)		文献来源
突变类型	突变位点	MIC值 (mg/L)	耐药	敏感	文献来源
非同义突变	Trp88STOP^**	>16	3	0	Schena等^[20]
		>4	2	0	Rancoita等^[24]
	Gly81Asp	>1.6	2	0	Yang等^[18]
	Gly81Ser	>0.4	31	0	Yang等^[18]
	Gly81Ser	<0.0125	0	4	Yang等^[18]
	Gly53Asp	0.25	3	0	Polsfuss等^[25]
	Leu107Pro	1	1	0	Fujiwara等^[15]
	Asn91Thr	>25	2	0	Fujiwara等^[15]
	Arg72Trp	<0.2	0	2	Schena等^[20]
	Glu83Asp	<0.2	0	1	Schena等^[20]
移码突变	434C缺失	>25	1	0	Fujiwara等^[15]
	215G缺失	>25	1	0	Fujiwara等^[15]
	252G—254A缺失	>25	1	0	Fujiwara等^[15]
	59—101缺失	>8	1	0	Fujiwara等^[15]
	91G缺失	≥0.12	1	0	Kardan-Yamchi等^[16]
	329C插入	>25	1	0	Fujiwara等^[15]
同义突变	Gly39Gly	<0.0125	0	5	Yang等^[18]

突变类型	突变位点	MIC值 (mg/L)	菌株(株)		文献来源
突变类型	突变位点	MIC值 (mg/L)	耐药	敏感	文献来源
非同义突变	Gly104Ser	>1	1	0	Ghodousi等^[26]
	Ala89Pro	>25	1	0	Fujiwara等^[15]
	Lys296Glu	<0.2	0	1	Schena等^[20]
	Lys270Met	<0.2	0	12	Schena等^[20]
移码突变	227C缺失	>25	1	0	Fujiwara等^[15]
	630G插入	>25	7	0	Fujiwara等^[15]
	G49fs^*	>0.32	1	0	Bloemberg等^[13]
同义突变	Phe320Phe	>0.2	9	0	Fujiwara等^[15]
		>8	1	0	Wen等^[17]
		<0.2	0	72	Schena等^[20]
	Tyr155Tyr	<0.2	0	3	Schena等^[20]

突变类型	突变位点	MIC值 (mg/L)	菌株(株)		文献来源
突变类型	突变位点	MIC值 (mg/L)	耐药	敏感	文献来源
非同义突变	Lys250STOP^**	>16	1	0	Schena等^[20]
	Asp106Gly	>25	1	0	Fujiwara等^[15]
	Asp49Thr	>0.32	3	0	Bloemberg等^[13]
	Asp49Tyr	≥2	1	0	Hoffmann等^[14]
	Glu249Lys	>16	1	0	Wen等^[17]
	Arg175His	≥2	1	0	Hoffmann等^[14]
		<0.016	0	9	Bloemberg等^[13]
	Gln120Arg	<0.2	0	3	Schena等^[20]
	Thr302Met	<0.2	0	2	Schena等^[20]
	Ala37Asp	<0.0125	0	1	Yang 等^[18]
	His295Tyr	<0.0125	0	1	Yang等^[18]
	Ile220Ser	<0.0125	0	1	Yang等^[18]
移码突变	272—275CAGG插入	>25	1	0	Fujiwara等^[15]
	452A缺失	>25	1	0	Fujiwara等^[15]
	222C, 223C缺失	>25	1	0	Fujiwara等^[15]
同义突变	Glu249Glu	<0.2	0	1	Schena等^[20]
	Pro144Pro	<0.2	0	3	Schena等^[20]
	Leu113Leu	<0.2	0	5	Schena等^[20] 和Yang等^[18]
	Asp63Asp	<0.0125	0	1	Yang等^[18]
	Pro181Pro	0.2	0	1	Yang等^[18]
	Ser194Ser	<0.0125	0	1	Yang等^[18]
	Ser267Ser	<0.0125	0	1	Yang等^[18]

突变类型	突变位点	MIC值 (mg/L)	菌株(株)		文献来源
突变类型	突变位点	MIC值 (mg/L)	耐药	敏感	文献来源
移码突变	1148C—1155G缺失	>0.39	1	0	Fujiwara等^[15]
	1263G—1264G缺失	≥25	1	0	Fujiwara等^[15]
同义突变	Thr92Thr	<0.015	0	1	Polsfuss等^[25]
非同义突变	Leu447Arg	<0.2	0	1	Schena等^[20]
	Lys448Arg	<0.2	0	1	Schena等^[20]
	Phe220Leu	<0.2	0	8	Schena等^[20]

突变类型	突变位点	MIC值 (mg/L)	菌株(株)		文献来源
突变类型	突变位点	MIC值 (mg/L)	耐药	敏感	文献来源
缺失突变	1339G缺失	>25	1	0	Fujiwara等^[15]
	811G,813C缺失	>25	1	0	Fujiwara等^[15]
	699C缺失	>25	1	0	Fujiwara等^[15]
	1638T缺失	>25	1	0	Fujiwara等^[15]
非同义突变	Arg220STOP^**	>25	1	0	Fujiwara等^[15]
	Val318Ile	32	2	0	Pang等^[19]
	Cys98Tyr	>25	1	0	Fujiwara等^[15]
	Leu53Pro	>25	1	0	Fujiwara等^[15]
	Arg536Leu	0.25	2	0	Rancoita等^[24]
	Thr273Ala	<0.2	0	5	Schena等^[20]
	Thr681Ile	<0.2	0	1	Schena等^[20]
同义突变	Leu55Leu	<0.2	0	2	Schena等^[20]
	Leu182Leu	<0.2	0	2	Schena等^[20]
	Asp67Asp	<0.2	0	1	Schena等^[20]
	Leu811Leu	<0.2	0	1	Schena等^[20]