Association Between Fatty Acid Metabolism Gene Mutations and Mycobacterium Tuberculosis Transmission Revealed by Whole Genome Sequencing

Overview

Journal BMC Microbiol

Publisher Biomed Central

Specialty Microbiology

Date 2023 Dec 1

PMID 38041005

Authors

Yameng Li

Xianglong Kong

Yifan Li

Ningning Tao

Tingting Wang

Yingying Li

Yawei Hou

Xuehan Zhu

Qilin Han

Yuzhen Zhang

Qiqi An

Yao Liu

Huaichen Li

Affiliations

Soon will be listed here.

Abstract

Background: Fatty acid metabolism greatly promotes the virulence and pathogenicity of Mycobacterium tuberculosis (M.tb). However, the regulatory mechanism of fatty acid metabolism in M.tb remains to be elucidated, and limited evidence about the effects of gene mutations in fatty acid metabolism on the transmission of M.tb was reported.

Results: Overall, a total of 3193 M.tb isolates were included in the study, of which 1596 (50%) were genomic clustered isolates. Most of the tuberculosis isolates belonged to lineage2(n = 2744,85.93%), followed by lineage4(n = 439,13.75%) and lineage3(n = 10,0.31%).Regression results showed that the mutations of gca (136,605, 317G > C, Arg106Pro; OR, 22.144; 95% CI, 2.591-189.272), ogt(1,477,346, 286G > C ,Gly96Arg; OR, 3.893; 95%CI, 1.432-10.583), and rpsA (1,834,776, 1235 C > T, Ala412Val; OR, 3.674; 95% CI, 1.217-11.091) were significantly associated with clustering; mutations in gca and rpsA were also significantly associated with clustering of lineage2. Mutation in arsA(3,001,498, 885 C > G, Thr295Thr; OR, 6.278; 95% CI, 2.508-15.711) was significantly associated with cross-regional clusters. We also found that 20 mutation sites were positively correlated with cluster size, while 11 fatty acid mutation sites were negatively correlated with cluster size.

Conclusion: Our research results suggested that mutations in genes related to fatty acid metabolism were related to the transmission of M.tb. This research could help in the future control of the transmission of M.tb.

Citing Articles

Correction: Association between fatty acid metabolism gene mutations and Mycobacterium tuberculosis transmission revealed by whole genome sequencing.

Li Y, Kong X, Li Y, Tao N, Wang T, Li Y BMC Microbiol. 2024; 24(1):2.

PMID: 38172663 PMC: 10763435. DOI: 10.1186/s12866-023-03158-4.

References

Rylance J, Pai M, Lienhardt C, Garner P . Priorities for tuberculosis research: a systematic review. Lancet Infect Dis. 2010; 10(12):886-92. PMC: 2992175. DOI: 10.1016/S1473-3099(10)70201-2. View

Linh N, Viney K, Gegia M, Falzon D, Glaziou P, Floyd K . World Health Organization treatment outcome definitions for tuberculosis: 2021 update. Eur Respir J. 2021; 58(2). DOI: 10.1183/13993003.00804-2021. View

Atamna-Mawassi H, Huberman-Samuel M, Hershcovitz S, Karny-Epstein N, Kola A, Lopez Cortes L . Interventions to reduce infections caused by multidrug resistant Enterobacteriaceae (MDR-E): A systematic review and meta-analysis. J Infect. 2021; 83(2):156-166. DOI: 10.1016/j.jinf.2021.05.005. View

Van Rie A, Enarson D . XDR tuberculosis: an indicator of public-health negligence. Lancet. 2006; 368(9547):1554-6. DOI: 10.1016/S0140-6736(06)69575-5. View

Singh V, Mani I, Chaudhary D, Somvanshi P . The β-ketoacyl-ACP synthase from Mycobacterium tuberculosis as potential drug targets. Curr Med Chem. 2011; 18(9):1318-24. DOI: 10.2174/092986711795029636. View

Nazarova E, Montague C, Huang L, La T, Russell D, VanderVen B . The genetic requirements of fatty acid import by within macrophages. Elife. 2019; 8. PMC: 6368401. DOI: 10.7554/eLife.43621. View

Laval T, Chaumont L, Demangel C . Not too fat to fight: The emerging role of macrophage fatty acid metabolism in immunity to Mycobacterium tuberculosis. Immunol Rev. 2021; 301(1):84-97. DOI: 10.1111/imr.12952. View

Kinsella R, Fitzpatrick D, Creevey C, McInerney J . Fatty acid biosynthesis in Mycobacterium tuberculosis: lateral gene transfer, adaptive evolution, and gene duplication. Proc Natl Acad Sci U S A. 2003; 100(18):10320-5. PMC: 193559. DOI: 10.1073/pnas.1737230100. View

Salaemae W, Azhar A, Booker G, Polyak S . Biotin biosynthesis in Mycobacterium tuberculosis: physiology, biochemistry and molecular intervention. Protein Cell. 2011; 2(9):691-5. PMC: 4875270. DOI: 10.1007/s13238-011-1100-8. View

10.

Grimes K, Aldrich C . A high-throughput screening fluorescence polarization assay for fatty acid adenylating enzymes in Mycobacterium tuberculosis. Anal Biochem. 2011; 417(2):264-73. PMC: 3152590. DOI: 10.1016/j.ab.2011.06.037. View

11.

Sacco E, Covarrubias A, OHare H, Carroll P, Eynard N, Jones T . The missing piece of the type II fatty acid synthase system from Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2007; 104(37):14628-33. PMC: 1976197. DOI: 10.1073/pnas.0704132104. View

12.

McKinney J, Honer zu Bentrup K, Munoz-Elias E, Miczak A, Chen B, Chan W . Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature. 2000; 406(6797):735-8. DOI: 10.1038/35021074. View

13.

Alonso Rodriguez N, Martinez Lirola M, Chaves F, Inigo J, Herranz M, Ritacco V . Differences in the robustness of clusters involving the Mycobacterium tuberculosis strains most frequently isolated from immigrant cases in Madrid. Clin Microbiol Infect. 2010; 16(10):1544-54. DOI: 10.1111/j.1469-0691.2010.03161.x. View

14.

Akhmetova A, Kozhamkulov U, Bismilda V, Chingissova L, Abildaev T, Dymova M . Mutations in the pncA and rpsA genes among 77 Mycobacterium tuberculosis isolates in Kazakhstan. Int J Tuberc Lung Dis. 2015; 19(2):179-84. DOI: 10.5588/ijtld.14.0305. View

15.

Vallejos-Sanchez K, Lopez J, Antiparra R, Toscano E, Saavedra H, Kirwan D . Mycobacterium tuberculosis ribosomal protein S1 (RpsA) and variants with truncated C-terminal end show absence of interaction with pyrazinoic acid. Sci Rep. 2020; 10(1):8356. PMC: 7239899. DOI: 10.1038/s41598-020-65173-z. View

16.

Nayak C, Chandra I, Singh S . An in silico pharmacological approach toward the discovery of potent inhibitors to combat drug resistance HIV-1 protease variants. J Cell Biochem. 2018; 120(6):9063-9081. DOI: 10.1002/jcb.28181. View

17.

Ebrahimi-Rad M, Bifani P, Martin C, Kremer K, Samper S, Rauzier J . Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family. Emerg Infect Dis. 2003; 9(7):838-45. PMC: 3023437. DOI: 10.3201/eid0907.020803. View

18.

Olano J, Lopez B, Reyes A, Lemos M, Correa N, Del Portillo P . Mutations in DNA repair genes are associated with the Haarlem lineage of Mycobacterium tuberculosis independently of their antibiotic resistance. Tuberculosis (Edinb). 2007; 87(6):502-8. DOI: 10.1016/j.tube.2007.05.011. View

19.

Mestre O, Luo T, Dos Vultos T, Kremer K, Murray A, Namouchi A . Phylogeny of Mycobacterium tuberculosis Beijing strains constructed from polymorphisms in genes involved in DNA replication, recombination and repair. PLoS One. 2011; 6(1):e16020. PMC: 3024326. DOI: 10.1371/journal.pone.0016020. View

20.

Miggiano R, Perugino G, Ciaramella M, Serpe M, Rejman D, Pav O . Crystal structure of Mycobacterium tuberculosis O6-methylguanine-DNA methyltransferase protein clusters assembled on to damaged DNA. Biochem J. 2015; 473(2):123-33. DOI: 10.1042/BJ20150833. View