Table 3.
Mycobacterium tuberculosis Virulence Genes Probably Acquired before MTB Speciation, and within MTBAP Lineage Evolution
| Label | Gene | Product | Function | Phenotype | Intracellular Survival | Animal Infection Model | Mcan | Mdec | Mshi | Mlac | Mriy | SGM |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rv0064 | — | Membrane protein | — | — | DC (Mendum et al. 2015) | — | ++ | ++ | − | − | + | − |
| Rv0071 | — | — | — | Deleted in L2/Beijing lineage M. tuberculosis strains (RD105) | M (Stewart et al. 2005) | — | − | + | − | − | − | − |
| Rv0240 | vapC24 | Toxin–antitoxin | Regulation | Induced under lysosomal stress conditions (Lin et al. 2016) | — | Macaque (Dutta et al. 2010) | − | − | − | + | − | − |
| Rv0348 | mosR | Transcriptional regulator | Regulation | Hypoxia responsive regulator (Abomoelak et al. 2009) | — | Mouse (Abomoelak et al. 2009) | − | − | ++ | − | − | − |
| Rv0590 | mce2B | Transporter | Transport (lipids) | Belongs to mce2 operon, involved in sulfolipid accumulation (Marjanovic et al. 2011) | — | Mouse (Marjanovic et al. 2010) | ++ | ++ | − | − | − | − |
| Rv0890c | — | Transcriptional regulator | Regulation | — | DC (Mendum et al. 2015) | — | ++ | ++ | − | − | − | − |
| Rv0893c | — | SAM methyltransferase | Secondary metabolism | — | M (Zhang et al. 2013) | — | ++ | ++ | − | − | − | − |
| Rv0895 | — | DAG-O-acyltransferase | Secondary metabolism (lipids) | — | M (Rengarajan et al. 2005) and DC (Mendum et al. 2015) | — | ++ | ++ | − | − | + | − |
| Rv0977 | PE_PGRS16 | PE_PPE | Secreted and surface proteins | — | DC (Mendum et al. 2015) | — | ++ | − | ++ | − | ++ | − |
| Rv1288 | — | Putative mycolyltransferase II | Secondary metabolism (lipids) | — | DC (Mendum et al. 2015) | — | ++ | ++ | − | − | + | − |
| Rv1359 | — | Transcriptional regulator | Regulation | — | DC (Mendum et al. 2015) | — | ++ | + | − | − | − | − |
| Rv1442 | bisC | Biotin sulfoxide reductase | Electron transfer activity | Oxidative stress resistance (putative) | DC (Mendum et al. 2015) | — | ++ | ++ | ++ (p) | + | ++ (p) | − |
| Rv1552 | frdA | Fumarate reductase subunit | Electron transfer activity | Hypoxia adaptation (Watanabe et al. 2011). Phagosome acidification arrest (Stewart et al. 2005) | DC (Mendum et al. 2015) | — | ++ | ++ | ++ | ++ | ++ | − |
| Rv1739c | sulP | Transporter | Transport | Sulfate uptake (Zolotarev et al. 2008) | DC (Mendum et al. 2015) | — | ++ | − | ++ | + | − | − |
| Rv1981c | nrdF1 | DNA-methylase | Regulation | Deleted in M. bovis BCG strains (RD2) | — | Mouse (Kozak et al. 2011) | ++ | ++ | − | − | + | − |
| Rv2275 | — | Cyclopeptide synthase | Secondary metabolism (mycocyclosin) | — | — | Mouse (Sassetti and Rubin 2003) | ++ | + | − | ++ | − | − |
| Rv2328 | PE23 | PE_PPE | Secreted and surface proteins | — | M (Stewart et al. 2005) | — | ++ | + | − | − | − | − |
| Rv2547 | vapC19 | Toxin–antitoxin | Regulation | Induced within granulomas (Hudock et al. 2017). | M (Stewart et al. 2005) | — | ++ | − | ++ | − | ++ | − |
| Rv2548 | vapB19 | Toxin–antitoxin | Regulation | Induced within granulomas (Hudock et al. 2017) | M (Stewart et al. 2005) | — | ++ | − | ++ | − | ++ | − |
| Rv2549c | vapC20 | Toxin–antitoxin | Regulation | — | M (Stewart et al. 2005) | — | ++ | − | ++ | − | ++ | − |
| Rv2550c | vapB20 | Toxin–antitoxin | Regulation | — | M (Stewart et al. 2005) | — | ++ | − | ++ | − | ++ | − |
| Rv2735c | — | — | — | — | DC (Mendum et al. 2015) | — | − | − | ++ | − | + | − |
| Rv2954c | — | Fucosyltransferase | Secondary metabolism (phenolglycolipid) | — | M (Rosas-Magallanes et al. 2007) | — | ++ | ++ | − | − | − | − |
| Rv2955c | — | Fucosyltransferase | Secondary metabolism (phenolglycolipid) | — | M (Rosas-Magallanes et al. 2007) | — | ++ | ++ | − | − | − | − |
| Rv3082c | virS | Transcriptional regulator | Regulation | Activation of Myma operon upon acidic pH and within phagosome (Singh et al. 2003) | M (Singh et al. 2005) | Guinea pig (Singh et al. 2005) | ++ | ++ | − | − | − | − |
| Rv3087 | — | DAG-O-acyltransferase | Secondary metabolism (lipids) | Belongs to Myma operon, involved in mycolic acid content (Singh et al. 2005) | M (Singh et al. 2005) | Mouse (Sassetti and Rubin 2003), Guinea pig (Singh et al. 2005) | ++ | ++ | − | − | − | − |
| Rv3179 | — | — | — | — | DC (Mendum et al. 2015) | — | ++ | − | − | + | + (p) | − |
| Rv3320c | vapC44 | Toxin–antitoxin | Regulation | Induced in nutrient starvation conditions (Albrethsen et al. 2013) | — | Mouse deltaMHC (Zhang et al. 2013) | ++ | − | − | + | + | − |
| Rv3343c | PPE54 | PE_PPE | Secreted and surface proteins | Oxidative stress resistance (Mestre et al. 2013) | DC (Mendum et al. 2015) | — | ++ | − | + | − | ++ | − |
| Rv3345c | PE_PGRS50 | PE_PPE | Secreted and surface proteins | — | DC (Mendum et al. 2015) | — | − | − | + | − | ++ | − |
| Rv3376 | — | Phosphatase | Secondary metabolism (diterpene 1TbAd) | Phagolysosome maturation arrest (Pethe et al. 2004) | M (Rengarajan et al. 2005) | — | ++ | + | − | + | − | − |
| Rv3377c | — | Diterpene synthase | Secondary metabolism (diterpene 1TbAd) | Phagolysosome maturation arrest (Pethe et al. 2004) | DC (Mendum et al. 2015) | — | ++ | ++ | − | ++ | − | − |
| Rv3476c | kgtP | Transporter | Transport | — | DC (Mendum et al. 2015) | — | ++ | ++ | − | − | − | − |
| Rv3487c | lipF | Lipase-esterase | Secondary metabolism (lipids) | Upregulated under acidic pH conditions (Richter and Saviola 2009) | — | Mouse (Camacho et al. 1999) | ++ | ++ | − | − | − | − |
| Rv3826 | fadD23 | Acyl-CoA synthetase | Secondary metabolism (sulfolipids) | Lower binding affinity for macrophages (Lynett and Stokes 2007) | DC (Mendum et al. 2015) | — | ++ | + | − | − | − | − |
Notes.—List of experimentally confirmed M. tuberculosis virulence genes that have at least one ortholog among other species of the MTBAP lineage (M. canettii is not included in the analysis) and no ortholog in any SGM depicted in the representative SGM database.
+
Presence of a putative ortholog by BBH-analysis.
++
Presence of a putative ortholog by BBH-analysis and synteny confirmation, -Absence of putative ortholog.
(p)Putative pseudogene.
Mtub, M. tuberculosis H37Rv; Mcan, M. canettii STBK; Mdec, M. decipiens; Mlac, M. lacus; Mriy, M. riyadhense.