Table 2.
Expression of genes involved in cobalamin metabolism in M. tuberculosis H37Rv based on RNA-Seq data.
| Gene name | Description | M. abscessus subsp. abscessus | M. smegmatis | |||||
|---|---|---|---|---|---|---|---|---|
| Locus | Average | SD | Locus | Average | SD | |||
| All genes | 201.88 | 547.4 | 147.33 | 607.04 | ||||
| Reference genes | ||||||||
| sigA | RNA polymerase sigma factor SigA (sigma-A) | MAB_3009 | 1213.5 | 31.5941962 | – | – | – | |
| dnaA | Chromosomal replication initiator protein DnaA | MAB_0001 | 285.34 | 4.39631664 | MSMEG_0093 | 94.66 | 39.15167557 | |
| ftsZ | Cell division protein FtsZ | MAB_2009 | 624.6633333 | 540.8220485 | MSMEG_4222 | 299.37 | 47.21376812 | |
| dnaG | Probable DNA primase DnaG | MAB_1708 | 154.3033333 | 9.405750014 | – | – | – | |
| rpoB | DNA-directed RNA polymerase (beta chain) RpoB (transcriptase beta chain) (RNA polymerase beta subunit) | MAB_3869c | 2151.213333 | 32.03047351 | MSMEG_1367 | 511.1433333 | 441.0141973 | |
| Aerobic pathway | ||||||||
| – | Precorrin-3B methylase, predicted replacement for cobF | – | – | – | – | – | – | |
| – | Bifunctional protein Rnase H/cobC | – | – | – | – | – | – | |
| cobA | Probable cob(I)alamin adenosyltransferase CobO | – | – | – | – | – | – | |
| cobB | Cobyrinic acid A,C-diamide synthase | MAB_3155c | 48.28333333 | 3.208899084 | MSMEG_2617 | 45.33666667 | 37.90995428 | |
| cobC | L-threonine 3-O-phosphate decarboxylase | MAB_1902 | 35.61333333 | 2.020948622 | – | – | – | |
| cobD | Adenosylcobinamide-phosphate synthase | MAB_1898 | 30.22333333 | 2.78363671 | MSMEG_4310 | 34.71333333 | 5.899494329 | |
| cobG | Precorrin-3B synthase | MAB_2200c | 44.81333333 | 10.51069138 | MSMEG_3871 | 43.05333333 | 9.251671921 | |
| cobH | Cobalt-precorrin-8 × methylmutase | MAB_2199c | 53.07 | 1.728670009 | MSMEG_3872 | 110.2366667 | 37.68649802 | |
| cobIJ | Cobalt-precorrin-2 C20-methyltransferase | – | – | – | MSMEG_3873 | 52.53333333 | 35.62759651 | |
| cobK | Cobalt-precorrin-6 × reductase | MAB_2197 | 118.63 | 8.898027871 | MSMEG_3875 | 40.99 | 6.827935266 | |
| cobL | Cobalt-precorrin-6y C5-methyltransferase | MAB_2195 | 95.33 | 10.65838168 | MSMEG_3878 | 33.24333333 | 4.282117856 | |
| cobM | Cobalt-precorrin-4 C11-methyltransferase | MAB_2196 | 190.0066667 | 34.70278423 | MSMEG_3877 | 40.97333333 | 4.718308313 | |
| cobN | Cobalt chelatase | MAB_2201 | 78.53 | 3.401043957 | MSMEG_3864 | 95.39333333 | 66.90839808 | |
| cobO | Cob(I)alamin adenosyltransferase | MAB_3156c | 94.59 | 20.00465696 | MSMEG_2616 | 150.34 | 26.29276136 | |
| cobQ1 | Cobyric acid synthase | – | – | – | MSMEG_2588 | 69.94666667 | 36.76729162 | |
| cobQ2 | Putative amidotransferase similar to cobyric acid synthase | MAB_0323c | 79.06333333 | 7.416537827 | – | – | – | |
| cobS | Cobalamin synthase | MAB_1952c | 98.49666667 | 3.519038694 | MSMEG_4277 | 35.19666667 | 3.883160225 | |
| cobT | Nicotinate-nucleotide–dimethylbenzimidazole phosphoribosyltransferase | MAB_1953c | 171.1133333 | 8.786639479 | MSMEG_4275 | 34.59333333 | 4.231930214 | |
| cobU | Adenosylcobinamide-phosphate guanylyltransferase | MAB_1954c | 191.44 | 15.12232456 | MSMEG_4274 | 109.1266667 | 5.803363967 | |
| pduO | Cob(I)alamin adenosyltransferase | – | – | – | MSMEG_1544 | 233.6766667 | 151.377732 | |
| bluB | 5,6-Dimethylbenzimidazole synthase | – | – | – | MSMEG_6053 | 97.35333333 | 36.85650056 | |
| Salvage pathway and transport | ||||||||
| bacA | Cobalamin transporter | – | – | – | – | – | – | |
| btuC | Iron ABC transporter permease | – | – | – | – | – | – | |
| Anaerobic pathway | ||||||||
| cbiX | Sirohydrochlorin ferrochelatase | – | – | – | – | – | – | |
| Urpoporfirynogen III pathway | ||||||||
| cysG | Multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | MAB_3143c | 95.06666667 | 7.895709806 | – | – | – | |
| cysH | Phosphoadenylyl-sulfate reductase | MAB_1661c | 174.4733333 | 18.36925783 | – | – | – | |
| gltX | Glutamyl-tRNA synthetase | MAB_3298c | 287.6433333 | 11.14623853 | MSMEG_2383 | 156.9933333 | 19.13254383 | |
| hemA | Glutamyl-tRNA reductase | MAB_3993c | 268.16 | 8.943438936 | MSMEG_0919 | 174.06 | 98.84548143 | |
| hemB | Probable delta-aminolevulinic acid dehydratase/porphobilinogen synthase | MAB_3990c | 349.51 | 54.2694122 | MSMEG_0956 | 201.9733333 | 27.76189895 | |
| hemC | Porphobilinogen deaminase | MAB_3992c | 638.4233333 | 82.95156076 | MSMEG_0953 | 374.95 | 313.6007022 | |
| hemD | Uroporphyrinogen III methyltransferase/synthase | – | – | – | MSMEG_0954 | 317.5766667 | 44.41745753 | |
| hemL | Glutamate-1-semialdehyde 2,1-aminomutase | – | – | – | MSMEG_0969 | 110.7066667 | 25.2243619 | |
| hemY | ChlI component of cobalt chelatase | MAB_2985c | 196.3366667 | 1.652099674 | – | – | – | |
| Vitamin B12 dependent enzymes | ||||||||
| metH | 5-Methyltetrahydrofolate–homocysteine methyltransferase | MAB_2129 | 605.9966667 | 39.45958101 | MSMEG_0093 | 94.66 | 39.15167557 | |
| mutB | Methylmalonyl-CoA mutase | MAB_2711c | 180.9466667 | 2.206928484 | – | – | – | |
| nrdZ | Ribonucleotide reductase of class II | – | – | – | – | – | – | |
| Gene name | Description | M. tuberculosis | ||||||
|---|---|---|---|---|---|---|---|---|
| Locus | Rich 7H9 broth | Cholesterol | Macrophages | |||||
| Average | SD | Average | SD | Average | SD | |||
| All genes | 256.0163876 | 551.1120531 | 256.01 | 764.53 | 256.0163722 | 1039.716894 | ||
| Reference genes | ||||||||
| sigA | RNA polymerase sigma factor SigA (sigma-A) | Rv2703 | 599.0566667 | 9.565264706 | 630.73 | 106.0339119 | 1776.92 | 403.8168363 |
| dnaA | Chromosomal replication initiator protein DnaA | Rv0001 | 131.0233333 | 1.802615384 | 532.06 | 40.00305738 | 579.74 | 351.8220045 |
| ftsZ | Cell division protein FtsZ | Rv2150c | 691.0366667 | 72.64343069 | 200.9733333 | 88.35943501 | 548.8 | 187.4937259 |
| dnaG | Probable DNA primase DnaG | Rv2343c | 104.9866667 | 2.321354968 | 91.05666667 | 42.02332077 | 118.2366667 | 98.34518335 |
| rpoB | DNA-directed RNA polymerase (beta chain) RpoB (transcriptase beta chain) (RNA polymerase beta subunit) | Rv0667 | 1650.64 | 35.26432853 | 701.45 | 81.97233192 | 438.5966667 | 130.3168532 |
| Aerobic pathway | ||||||||
| – | Precorrin-3B methylase, predicted replacement for cobF | Rv2067c | 104.4866667 | 4.4877339 | 32.90666667 | 33.05350242 | 283.67 | 60.07031935 |
| – | Bifunctional protein Rnase H/cobC | Rv2228c | 91.63333333 | 0.241430919 | 36.25333333 | 20.75320752 | 0 | 0 |
| cobA | Probable cob(I)alamin adenosyltransferase CobO | Rv2849c | 77.32666667 | 3.099519676 | 74.58333333 | 10.26311302 | 507.9333333 | 458.6724143 |
| cobB | Cobyrinic acid A,C-diamide synthase | Rv2848c | 51.04333333 | 0.651783877 | 60.56666667 | 31.54769652 | 0 | 0 |
| cobC | L-threonine 3-O-phosphate decarboxylase | Rv2231c | 78.29 | 3.854279007 | 37.80333333 | 27.56415224 | 0 | 0 |
| cobD | Adenosylcobinamide-phosphate synthase | Rv2236c | 58.52333333 | 1.689108904 | 1.9 | 1.064831755 | 81.79333333 | 115.6732413 |
| cobG | Precorrin-3B synthase | Rv2064 | 183.29 | 4.164956983 | 33.45 | 26.14527236 | 133.5466667 | 188.8635072 |
| cobH | Cobalt-precorrin-8 × methylmutase | Rv2065 | 178.23 | 4.38254112 | 0.593333333 | 0.839100047 | 0 | 0 |
| cobIJ | Cobalt-precorrin-2 C20-methyltransferase | Rv2066 | 150.18 | 9.995749096 | 74.32666667 | 8.916786915 | 72.98 | 58.51295412 |
| cobK | Cobalt-precorrin-6 × reductase | Rv2070c | 89.46666667 | 8.680419857 | 42.11333333 | 30.69800681 | 419.98 | 124.7825583 |
| cobL | Cobalt-precorrin-6y C5-methyltransferase | Rv2072c | 51.73666667 | 2.388616522 | 56.36333333 | 44.1996458 | 219.44 | 310.3350241 |
| cobM | Cobalt-precorrin-4 C11-methyltransferase | Rv2071c | 32.80333333 | 1.224100577 | 63.16666667 | 39.84209192 | 0 | 0 |
| cobN | Cobalt chelatase | Rv2062c | 101.4866667 | 3.59177146 | 46.24666667 | 13.10098554 | 167.3266667 | 118.4526528 |
| cobO | Cob(I)alamin adenosyltransferase | Rv2849c | 77.32666667 | 3.099519676 | 74.58333333 | 10.26311302 | 507.9333333 | 458.6724143 |
| cobQ1 | Cobyric acid synthase | Rv0255c | 83.46333333 | 4.16039528 | 60.76333333 | 17.12575124 | 0 | 0 |
| cobQ2 | Putative amidotransferase similar to cobyric acid synthase | Rv3713 | 178.4833333 | 3.066206487 | 95.84333333 | 45.96082849 | 104.7666667 | 148.1624409 |
| cobS | Cobalamin synthase | Rv2208 | 280.7333333 | 5.75070044 | 38.15 | 35.52983347 | 228.8033333 | 323.5767771 |
| cobT | Nicotinate-nucleotide–dimethylbenzimidazole phosphoribosyltransferase | Rv2207 | 341.1866667 | 6.934096112 | 10.67 | 6.638649461 | 70.94666667 | 100.3337382 |
| cobU | Adenosylcobinamide-phosphate guanylyltransferase | Rv0254c | 46.93666667 | 5.12625486 | 171.9133333 | 89.37495001 | 138.89 | 196.4201217 |
| pduO | Cob(I)alamin adenosyltransferase | Rv1314c | 88.84 | 1.75789647 | 51.02 | 33.75337119 | 125.2866667 | 177.1821032 |
| bluB | 5,6-Dimethylbenzimidazole synthase | Rv0306 | 50.93 | 3.946044433 | 74.76 | 42.37912772 | 0 | 0 |
| Salvage pathway and transport | ||||||||
| bacA | Cobalamin transporter | Rv1819c | 112.5766667 | 3.598373089 | 27.63 | 21.66365312 | 82.66333333 | 59.02668455 |
| btuC | Iron ABC transporter permease | Rv2060 | 191.76 | 5.638421765 | 296.6266667 | 162.4777085 | 106.7166667 | 150.9201573 |
| Anaerobic pathway | ||||||||
| cbiX | Sirohydrochlorin ferrochelatase | Rv0259c | 12.73 | 1.498465882 | 0 | 0 | 0 | 0 |
| Urpoporfirynogen III pathway | ||||||||
| cysG | Multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | Rv2847c | 68.92 | 5.318890862 | 36.77 | 10.84717782 | 63.26 | 89.46314996 |
| cysH | Phosphoadenylyl-sulfate reductase | Rv2392 | 312.9333333 | 19.43125032 | 503.0566667 | 166.2576146 | 0 | 0 |
| gltX | Glutamyl-tRNA synthetase | Rv2992c | 170.96 | 11.21727537 | 89.43333333 | 42.90810128 | 107.7533333 | 76.94248949 |
| hemA | Glutamyl-tRNA reductase | Rv0509 | 612.7766667 | 65.26401271 | 698.94 | 222.6659401 | 362.77 | 513.034254 |
| hemB | Probable delta-aminolevulinic acid dehydratase/porphobilinogen synthase | Rv0512 | 279.2466667 | 19.95736511 | 165.0033333 | 36.41366075 | 160.32 | 114.4782576 |
| hemC | Porphobilinogen deaminase | Rv0510 | 627.0233333 | 64.43651415 | 435.5433333 | 115.7868324 | 161.2566667 | 114.1554689 |
| hemD | Uroporphyrinogen III methyltransferase/synthase | Rv0511 | 640.4733333 | 56.28158037 | 342.2533333 | 64.04123949 | 138.85 | 9.488702054 |
| hemL | Glutamate-1-semialdehyde 2,1-aminomutase | Rv0524 | 437.8066667 | 25.11909809 | 114.9666667 | 72.38097832 | 391.8 | 135.6539762 |
| hemY | ChlI component of cobalt chelatase | Rv2850c | 135.66 | 6.78823001 | 38.01666667 | 3.454488224 | 81.53333333 | 115.3055458 |
| Vitamin B12 dependent enzymes | ||||||||
| metH | 5-Methyltetrahydrofolate–homocysteine methyltransferase | Rv2124c | 155.78 | 9.823003614 | 311.4966667 | 16.31473431 | 128.15 | 45.50090622 |
| mutB | Methylmalonyl-CoA mutase | Rv1493 | 48.83 | 1.851323851 | 139.7433333 | 70.5155852 | 38.08333333 | 53.8579665 |
| nrdZ | Ribonucleotide reductase of class II | Rv0570 | 60.79333333 | 1.360890232 | 366.2433333 | 120.7928051 | 119.6 | 101.265619 |