Comprehensive Pan-genome Analysis of Mycobacterium Marinum: Insights into Genomic Diversity, Evolution, and Pathogenicity

Overview

Journal Sci Rep

Specialty Science

Date 2024 Nov 12

PMID 39532890

Authors

Meng Zhang

Sabir Adroub

Roy Ummels

Mohammed Asaad

Lei Song

Arnab Pain

Wilbert Bitter

Qingtian Guan

Abdallah M Abdallah

Affiliations

Soon will be listed here.

Abstract

Mycobacteria is a diverse genus that includes both innocuous environmental species and serious pathogens like Mycobacterium tuberculosis, Mycobacterium leprae, and Mycobacterium ulcerans, the causative agents of tuberculosis, leprosy, and Buruli ulcer, respectively. This study focuses on Mycobacterium marinum, a closely related species known for its larger genome and ability to infect ectothermic species and cooler human extremities. Utilizing whole-genome sequencing, we conducted a comprehensive pan-genome analysis of 100 M. marinum strains, exploring genetic diversity and its impact on pathogenesis and host specificity. Our findings highlight significant genomic diversity, with clear distinctions in core, dispensable, and unique genes among the isolates. Phylogenetic analysis revealed a broad distribution of genetic lineages, challenging previous classifications into distinct clusters. Additionally, we examined the synteny and diversity of the virulence factor CpnT, noting a wide range of C-terminal domain variations across strains, which points to potential adaptations in pathogenic mechanisms. This study enhances our understanding of M. marinum's genomic architecture and its evolutionary relationship with other mycobacterial pathogens, providing insights that could inform disease control strategies for M. tuberculosis and other mycobacteria.

References

Stinear T, Seemann T, Harrison P, Jenkin G, Davies J, Johnson P . Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis. Genome Res. 2008; 18(5):729-41. PMC: 2336800. DOI: 10.1101/gr.075069.107. View

Muzzi A, Masignani V, Rappuoli R . The pan-genome: towards a knowledge-based discovery of novel targets for vaccines and antibacterials. Drug Discov Today. 2007; 12(11-12):429-39. DOI: 10.1016/j.drudis.2007.04.008. View

Cantalapiedra C, Hernandez-Plaza A, Letunic I, Bork P, Huerta-Cepas J . eggNOG-mapper v2: Functional Annotation, Orthology Assignments, and Domain Prediction at the Metagenomic Scale. Mol Biol Evol. 2021; 38(12):5825-5829. PMC: 8662613. DOI: 10.1093/molbev/msab293. View

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

Wang Y, Tang Y, Lin C, Zhang J, Mai J, Jiang J . Crosstalk between the ancestral type VII secretion system ESX-4 and other T7SS in . iScience. 2022; 25(1):103585. PMC: 8718981. DOI: 10.1016/j.isci.2021.103585. View

Tettelin H, Riley D, Cattuto C, Medini D . Comparative genomics: the bacterial pan-genome. Curr Opin Microbiol. 2008; 11(5):472-7. DOI: 10.1016/j.mib.2008.09.006. View

Danilchanka O, Sun J, Pavlenok M, Maueroder C, Speer A, Siroy A . An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity. Proc Natl Acad Sci U S A. 2014; 111(18):6750-5. PMC: 4020113. DOI: 10.1073/pnas.1400136111. View

Hoffmann C, Leis A, Niederweis M, Plitzko J, Engelhardt H . Disclosure of the mycobacterial outer membrane: cryo-electron tomography and vitreous sections reveal the lipid bilayer structure. Proc Natl Acad Sci U S A. 2008; 105(10):3963-7. PMC: 2268800. DOI: 10.1073/pnas.0709530105. View

Nguyen L, Schmidt H, von Haeseler A, Minh B . IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol. 2014; 32(1):268-74. PMC: 4271533. DOI: 10.1093/molbev/msu300. View

10.

Tufariello J, Chapman J, Kerantzas C, Wong K, Vilcheze C, Jones C . Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulence. Proc Natl Acad Sci U S A. 2016; 113(3):E348-57. PMC: 4725510. DOI: 10.1073/pnas.1523321113. View

11.

Khan S, Ahmad F, Ikram Ansari M, Ashfaque M, Islam M, Khubaib M . Toxin-Antitoxin system of Mycobacterium tuberculosis: Roles beyond stress sensor and growth regulator. Tuberculosis (Edinb). 2023; 143:102395. DOI: 10.1016/j.tube.2023.102395. View

12.

Das S, Pettersson B, Krishna Behra P, Mallick A, Cheramie M, Ramesh M . Extensive genomic diversity among Mycobacterium marinum strains revealed by whole genome sequencing. Sci Rep. 2018; 8(1):12040. PMC: 6089878. DOI: 10.1038/s41598-018-30152-y. View

13.

Veyrier F, Pletzer D, Turenne C, Behr M . Phylogenetic detection of horizontal gene transfer during the step-wise genesis of Mycobacterium tuberculosis. BMC Evol Biol. 2009; 9:196. PMC: 3087520. DOI: 10.1186/1471-2148-9-196. View

14.

Becq J, Gutierrez M, Rosas-Magallanes V, Rauzier J, Gicquel B, Neyrolles O . Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli. Mol Biol Evol. 2007; 24(8):1861-71. DOI: 10.1093/molbev/msm111. View

15.

Maione D, Margarit I, Rinaudo C, Masignani V, Mora M, Scarselli M . Identification of a universal Group B streptococcus vaccine by multiple genome screen. Science. 2005; 309(5731):148-50. PMC: 1351092. DOI: 10.1126/science.1109869. View

16.

Li W, Godzik A . Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics. 2006; 22(13):1658-9. DOI: 10.1093/bioinformatics/btl158. View

17.

Clemmensen H, Knudsen N, Rasmussen E, Winkler J, Rosenkrands I, Ahmad A . An attenuated Mycobacterium tuberculosis clinical strain with a defect in ESX-1 secretion induces minimal host immune responses and pathology. Sci Rep. 2017; 7:46666. PMC: 5402389. DOI: 10.1038/srep46666. View

18.

Lechner M, Findeiss S, Steiner L, Marz M, Stadler P, Prohaska S . Proteinortho: detection of (co-)orthologs in large-scale analysis. BMC Bioinformatics. 2011; 12:124. PMC: 3114741. DOI: 10.1186/1471-2105-12-124. View

19.

Dunn B, Richter C, Kvitek D, Pugh T, Sherlock G . Analysis of the Saccharomyces cerevisiae pan-genome reveals a pool of copy number variants distributed in diverse yeast strains from differing industrial environments. Genome Res. 2012; 22(5):908-24. PMC: 3337436. DOI: 10.1101/gr.130310.111. View

20.

Uchiya K, Tomida S, Nakagawa T, Asahi S, Nikai T, Ogawa K . Comparative genome analyses of Mycobacterium avium reveal genomic features of its subspecies and strains that cause progression of pulmonary disease. Sci Rep. 2017; 7:39750. PMC: 5206733. DOI: 10.1038/srep39750. View