Identification and in silico functional prediction of lineage-specific SNPs distributed in DosR-related proteins and resuscitation-promoting factor proteins of Mycobacterium tuberculosis
One-third of the world population is infected by Mycobacterium tuberculosis, which may persist in the latent or dormant state. Bacteria can shift to dormancy when encountering harsh conditions such as low oxygen, nutrient starvation, high acidity and host immune defenses. Genes related to the dorman...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844020325871 |
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| author | Pornpen Tantivitayakul Tada Juthayothin Wuthiwat Ruangchai Nat Smittipat Areeya Disratthakit Surakameth Mahasirimongkol Katsushi Tokunaga Prasit Palittapongarnpim |
| author_facet | Pornpen Tantivitayakul Tada Juthayothin Wuthiwat Ruangchai Nat Smittipat Areeya Disratthakit Surakameth Mahasirimongkol Katsushi Tokunaga Prasit Palittapongarnpim |
| author_sort | Pornpen Tantivitayakul |
| collection | DOAJ |
| description | One-third of the world population is infected by Mycobacterium tuberculosis, which may persist in the latent or dormant state. Bacteria can shift to dormancy when encountering harsh conditions such as low oxygen, nutrient starvation, high acidity and host immune defenses. Genes related to the dormancy survival regulator (DosR) regulon are responsible for the inhibition of aerobic respiration and replication, which is required to enter dormancy. Conversely, resuscitation-promoting factor (rpf) proteins participate in reactivation from dormancy and the development of active tuberculosis (TB). Many DosR regulon and rpf proteins are immunodominant T cell antigens that are highly expressed in latent TB infection. They could serve as TB vaccine candidates and be used for diagnostic development. We explored the genetic polymorphisms of 50 DosR-related genes and 5 rpf genes among 1,170 previously sequenced clinical M. tuberculosis genomes. Forty-three lineage- or sublineage-specific nonsynonymous single nucleotide polymorphisms (nsSNPs) were identified. Ten nsSNPs were specific to all Mtb isolates belonging to lineage 1 (L1). Two common sublineages, the Beijing family (L2.2) and EAI2 (L1.2.1), differed at as many as 26 lineage- or sublineage-specific SNPs. DosR regulon genes related to membrane proteins and the rpf family possessed mean dN/dS ratios greater than one, suggesting that they are under positive selection. Although the T cell epitope regions of DosR-related and rpf antigens were quite conserved, we found that the epitopes in L1 had higher rates of genetic polymorphisms than the other lineages. Some mutations in immunogenic epitopes of the antigens were specific to particular M. tuberculosis lineages. Therefore, the genetic diversity of the DosR regulon and rpf proteins might impact the adaptation of M. tuberculosis to the dormant state and the immunogenicity of latency antigens, which warrants further investigation. |
| first_indexed | 2024-12-14T14:37:44Z |
| format | Article |
| id | doaj.art-c22b8f8291b74bfe99fb2163af07511a |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-14T14:37:44Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-c22b8f8291b74bfe99fb2163af07511a2022-12-21T22:57:32ZengElsevierHeliyon2405-84402020-12-01612e05744Identification and in silico functional prediction of lineage-specific SNPs distributed in DosR-related proteins and resuscitation-promoting factor proteins of Mycobacterium tuberculosisPornpen Tantivitayakul0Tada Juthayothin1Wuthiwat Ruangchai2Nat Smittipat3Areeya Disratthakit4Surakameth Mahasirimongkol5Katsushi Tokunaga6Prasit Palittapongarnpim7Department of Oral Microbiology, Faculty of Dentistry, Mahidol University, Bangkok, 10400, ThailandNational Centre for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Phaholyothin Road, Pathumthani, ThailandPornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok, ThailandNational Centre for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Phaholyothin Road, Pathumthani, ThailandDepartment of Medical Sciences, Ministry of Public Health, Tiwanon Road, Nonthaburi, ThailandDepartment of Medical Sciences, Ministry of Public Health, Tiwanon Road, Nonthaburi, ThailandGenome Medical Science Project, National Center for Global Health and Medicine, Tokyo, JapanPornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok, Thailand; National Centre for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Phaholyothin Road, Pathumthani, Thailand; Corresponding author.One-third of the world population is infected by Mycobacterium tuberculosis, which may persist in the latent or dormant state. Bacteria can shift to dormancy when encountering harsh conditions such as low oxygen, nutrient starvation, high acidity and host immune defenses. Genes related to the dormancy survival regulator (DosR) regulon are responsible for the inhibition of aerobic respiration and replication, which is required to enter dormancy. Conversely, resuscitation-promoting factor (rpf) proteins participate in reactivation from dormancy and the development of active tuberculosis (TB). Many DosR regulon and rpf proteins are immunodominant T cell antigens that are highly expressed in latent TB infection. They could serve as TB vaccine candidates and be used for diagnostic development. We explored the genetic polymorphisms of 50 DosR-related genes and 5 rpf genes among 1,170 previously sequenced clinical M. tuberculosis genomes. Forty-three lineage- or sublineage-specific nonsynonymous single nucleotide polymorphisms (nsSNPs) were identified. Ten nsSNPs were specific to all Mtb isolates belonging to lineage 1 (L1). Two common sublineages, the Beijing family (L2.2) and EAI2 (L1.2.1), differed at as many as 26 lineage- or sublineage-specific SNPs. DosR regulon genes related to membrane proteins and the rpf family possessed mean dN/dS ratios greater than one, suggesting that they are under positive selection. Although the T cell epitope regions of DosR-related and rpf antigens were quite conserved, we found that the epitopes in L1 had higher rates of genetic polymorphisms than the other lineages. Some mutations in immunogenic epitopes of the antigens were specific to particular M. tuberculosis lineages. Therefore, the genetic diversity of the DosR regulon and rpf proteins might impact the adaptation of M. tuberculosis to the dormant state and the immunogenicity of latency antigens, which warrants further investigation.http://www.sciencedirect.com/science/article/pii/S2405844020325871MicrobiologyGeneticsMolecular biologyInfectious diseaseLineage-specific SNPDosR-related proteins |
| spellingShingle | Pornpen Tantivitayakul Tada Juthayothin Wuthiwat Ruangchai Nat Smittipat Areeya Disratthakit Surakameth Mahasirimongkol Katsushi Tokunaga Prasit Palittapongarnpim Identification and in silico functional prediction of lineage-specific SNPs distributed in DosR-related proteins and resuscitation-promoting factor proteins of Mycobacterium tuberculosis Heliyon Microbiology Genetics Molecular biology Infectious disease Lineage-specific SNP DosR-related proteins |
| title | Identification and in silico functional prediction of lineage-specific SNPs distributed in DosR-related proteins and resuscitation-promoting factor proteins of Mycobacterium tuberculosis |
| title_full | Identification and in silico functional prediction of lineage-specific SNPs distributed in DosR-related proteins and resuscitation-promoting factor proteins of Mycobacterium tuberculosis |
| title_fullStr | Identification and in silico functional prediction of lineage-specific SNPs distributed in DosR-related proteins and resuscitation-promoting factor proteins of Mycobacterium tuberculosis |
| title_full_unstemmed | Identification and in silico functional prediction of lineage-specific SNPs distributed in DosR-related proteins and resuscitation-promoting factor proteins of Mycobacterium tuberculosis |
| title_short | Identification and in silico functional prediction of lineage-specific SNPs distributed in DosR-related proteins and resuscitation-promoting factor proteins of Mycobacterium tuberculosis |
| title_sort | identification and in silico functional prediction of lineage specific snps distributed in dosr related proteins and resuscitation promoting factor proteins of mycobacterium tuberculosis |
| topic | Microbiology Genetics Molecular biology Infectious disease Lineage-specific SNP DosR-related proteins |
| url | http://www.sciencedirect.com/science/article/pii/S2405844020325871 |
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