Table 2 SNPs significantly associated with classification as MBO by Subsequent statistical test

22,264

0

0.948

4100

2080

172

1

Rv0018c

PstP

Involved in regulation (using dephosphorylation of a specific phosphorylated substrate)

Required for survival in murine macrophages (Rengarajan 2005)

Synonymous

23,714

0

0.951

4100

2100

161

1

Rv0019c

FhaB

Conserved protein with FHA domain, FhaB

Required for survival in murine macrophages (Rengarajan 2005)

Synonymous

147,873

0

0.998

4100

2250

9

3

Intergenic, upstream of elongation factor G FusA2 (Rv0120c)

Intergenic

181,672

0

0.951

4100

2100

161

1

Rv0153c

PtbB

Phosphotyrosine protein phosphatase PTPB (protein-tyrosine-phosphatase) (PTPase)

Required for growth on cholesterol (Griffin 2011)

Asp105Gly

184,727

0

0.998

4100

2250

9

3

Rv0156

PntAb

Probable NAD(P) transhydrogenase (subunit alpha) PntAb [second part; integral membrane protein] (pyridine nucleotide transhydrogenase subunit alpha) (nicotinamide nucleotide transhydrogenase subunit alpha)

Tyr2Cys

212,254

0

0.951

4100

2100

161

1

Intergenic, upstream of transmembrane protein (Rv0180)

Intergenic

217,863

0

0.951

4100

2100

160

1

Rv0186

BglS

Possibly involved in degradation [catalytic activity: hydrolysis of terminal, non-reducing beta-D-glucose residues with release of beta-D-glucose]

Pro532Arg

262,160

0

0.997

4100

2250

9

8

Rv0218

Probable conserved transmembrane protein

Essential in murine spleen (Sassetti and Rubin, 2003)

Asp413Asn

268,277

0

0.998

4100

2250

9

3

Rv0224c

Possible methyltransferase (methylase)

In vitro essential per multiple studies (Minato 2019; DeJesus 2017; Sassetti 2003; Griffin 2011)

Phe117Leu

277,862

0

0.998

4100

2250

9

3

Intergenic, downstream of FadE4 (Rv0231) and upstream of probable transcriptional regulatory protein (probably TetR/AcrR-family) (Rv0232)

Intergenic

294,198

0

0.997

4100

2250

9

8

Rv0244c

FadE5

Probable acyl-CoA dehydrogenase FadE5

Required for growth on cholesterol (Griffin 2011)

Glu479Ala

386,060

0

0.997

4100

2250

9

8

Intergenic, upstream of glpQ2 (Rv0317c)

Intergenic

397,386

0

0.951

4100

2100

160

1

Intergenic, downstream of putative dehydrogenase/reductase (Rv0331) and upstream of hypothetical protein (Rv0332)

Intergenic

398,034

0

0.997

4100

2250

9

8

Rv0332

Conserved protein

Glu198Gly

411,100

0

0.948

4100

2090

171

2

Rv0342

IniA

Isoniazid inductible gene protein IniA

Asn88Ser

1,027,445

0

0.997

4100

2250

9

8

Rv0921

Possible resolvase for IS1535

Synonymous

1,029,936

0

0.951

4100

2100

161

1

Rv0923c

Conserved hypothetical protein

Synonymous

1,125,316

0

0.951

4100

2100

161

1

Rv1006

Unknown protein

Disruption provides growth advantage (DeJesus 2017)

Pro535Ser

1,129,160

0

0.997

4100

2250

9

9

Rv1010

KsgA

Probable dimethyladenosine transferase KsgA (S-adenosylmethionine-6-N', N'-adenosyl(rRNA) dimethyltransferase) (16S rRNA dimethylase) (high level kasugamycin resistance protein KsgA) (kasugamycin dimethyltransferase)

Synonymous

1,129,160

0

0.997

4100

2250

9

9

Rv1009

RpfB

Probable resuscitation-promoting factor RpfB

Ala357Val

1,234,657

0

0.998

4100

2250

9

3

Rv1108c

XseA

Probable exodeoxyribonuclease VII (large subunit) XseA (exonuclease VII large subunit)

Synonymous

1,260,537

0

0.951

4100

2100

161

1

Rv1133c

MetE

Probable 5-methyltetrahydropteroyltriglutamate–homocysteine methyltransferase MetE (methionine synthase, vitamin-B12 independent isozyme)

In vitro essential (DeJesus 2017; Sassetti 2003; Griffin 2011), non-essential in rich media (Minato 2019)

Synonymous

1,307,958

0

0.951

4100

2100

161

1

Rv1175c

FadH

Probable NADPH dependent 2,4-dienoyl-CoA reductase FadH (2,4-dienoyl coenzyme A reductase) (4-enoyl-CoA reductase)

Thr90Asn

1,377,140

0

0.948

4100

2080

172

1

Rv1234

Probable transmembrane protein

Glu55Glu

1,393,003

0

0.951

4100

2100

161

1

Rv1248c

Multifunctional alpha-ketoglutarate metabolic enzyme

In vitro essential per multiple studies (Minato 2019; Sassetti 2003; Griffin 2011; Carvalho 2010)

Glu17Ala

1,425,641

0

0.951

4100

2100

161

1

Rv1276c

Conserved hypothetical protein

Thr92Ser

1,458,076

0

0.951

4100

2100

161

1

Rv1301

Conserved protein

In vitro essential (Sassetti 2003; Griffin 2011), non-essential in rich media (Minato 2019)

Synonymous

1,478,312

0

0.998

4100

2250

9

3

Rv1317c

AlkA

Probable bifunctional regulatory protein and DNA repair enzyme AlkA (regulatory protein of adaptative response) (methylphosphotriester-DNA–protein-cysteine S-methyltransferase)

Synonymous

1,496,289

0

0.997

4100

2250

9

8

Rv1328

GlgP

Probable glycogen phosphorylase GlgP

Val576Phe

1,499,291

0

0.998

4100

2250

9

4

Rv1330c

PncB1

Nicotinic acid phosphoribosyltransferase PncB1

Gly423Gly

1,562,049

0

0.997

4100

2250

9

8

Rv1387

PPE20

PPE family protein PPE20

Val94Ala

1,609,445

0

0.948

4100

2080

172

1

Rv1431

Conserved membrane protein

Lys455Gln

1,671,658

0

0.997

4100

2250

9

8

Rv1481

Probable membrane protein

In vitro essential per multiple studies (Minato 2019; DeJesus 2017; Griffin 2011)

Synonymous

1,681,928

0

0.951

4100

2100

161

1

Rv1491c

Conserved membrane protein

Synonymous

1,684,979

0

0.948

4100

2080

172

1

Rv1493

MutB

Probable methylmalonyl-CoA mutase large subunit MutB (MCM)

Synonymous

1,739,294

0

0.998

4100

2250

9

3

Rv1536

IleS

Isoleucyl-tRNA synthetase IleS

In vitro essential per multiple studies (Minato 2019; DeJesus 2017; Griffin 2011; Lamichhane 2003)

Pro926Ala

1,754,572

0

0.951

4100

2100

161

1

Rv1550

FadD11

Probable fatty-acid-CoA ligase FadD11 (fatty-acid-CoA synthetase) (fatty-acid-CoA synthase)

Leu286Ser

1,766,620

0

0.951

4100

2100

161

1

Rv1562c

TreZ

Maltooligosyltrehalose trehalohydrolase TreZ

Ala175Thr

1,794,234

0

0.948

4100

2080

172

1

Rv1593c

Conserved protein

Synonymous

1,804,248

0

0.951

4100

2100

161

1

Rv1604

ImpA

Probable inositol-monophosphatase ImpA (imp)

Synonymous

1,804,315

0

0.997

4100

2250

9

8

Rv1604

ImpA

Probable inositol-monophosphatase ImpA (imp)

Tyr93His

1,830,295

0

0.998

4100

2250

9

3

Rv1628c

Conserved protein

Synonymous

1,834,859

0

0.951

4100

2100

161

1

Rv1630

RpsA

30S ribosomal protein S1 RpsA

In vitro essential per multiple studies (Minato 2019; DeJesus 2017; Griffin 2011; Sassetti 2003)

Ala440Thr

1,971,029

0

0.997

4100

2250

9

8

Rv1744c

Probable membrane protein

Arg121Gln

2,013,589

0

0.951

4100

2100

160

1

Rv1779c

Possible integral membrane protein

Synonymous

2,082,865

0

0.997

4100

2250

10

8

Rv1836c

Conserved protein

Arg591His

2,092,688

0

0.948

4100

2080

172

1

Rv1843c

GuaB1

Probable inosine-5'-monophosphate dehydrogenase GuaB1(imp dehydrogenase) (IMPDH) (IMPD)

Disruption provides growth advantage (DeJesus 2017)

Synonymous

2,104,270

0

0.997

4100

2250

9

8

Rv1856c

Possible oxidoreductase

Disruption provides growth advantage (DeJesus 2017)

Arg185His

2,280,081

0

0.951

4100

2100

161

1

Rv2032

Acg

Conserved protein Acg

Pro318Leu

2,475,116

0

0.997

4100

2250

9

8

Rv2210c

IlvE

Branched-chain amino acid transaminase IlvE

In vitro essential (Sassetti 2003; Griffin 2011; DeJesus 2017), non-essential in rich media (Minato 2019)

Synonymous

2,475,888

0

0.998

4100

2250

9

3

Rv2210c

IlvE

Branched-chain amino acid transaminase IlvE

In vitro essential (Sassetti 2003; Griffin 2011; DeJesus 2017), non-essential in rich media (Minato 2019)

Glu28Ala

2,502,757

0

0.951

4100

2100

161

1

Rv2229c

Conserved protein

Arg239Gln

2,528,773

0

0.998

4100

2250

9

3

Rv2254c

Probable integral membrane protein

Ala68Val

2,529,798

0

0.951

4100

2100

161

1

Rv2256c

Conserved hypothetical protein

Ala26Gly

2,606,813

0

0.951

4100

2100

161

1

Rv2333c

Stp

Integral membrane drug efflux protein Stp

His503Gln

2,646,542

0

0.951

4100

2100

161

1

Rv2364c

Era

Probable GTP-binding protein Era

In vitro essential (Sassetti 2003; Griffin 2011), non-essential in rich media (Minato 2019)

Synonymous

2,658,676

0

0.998

4100

2250

9

3

Rv2379c

MbtF

Peptide synthetase MbtF (peptide synthase)

Ala1137Val

2,659,542

0

0.951

4100

2100

161

1

Rv2379c

MbtF

Peptide synthetase MbtF (peptide synthase)

Synonymous

2,682,593

0

0.998

4100

2250

9

3

Rv2388c

HemN

Probable oxygen-independent coproporphyrinogen III oxidase HemN (coproporphyrinogenase) (coprogen oxidase)

Essential in murine spleen (Sassetti and Rubin, 2003)

Ala184Thr

2,692,875

0

0.997

4100

2250

9

8

Rv2396

AprC

Acid and phagosome regulated protein C, PE-PGRS family protein PE_PGRS41

Ser26Asn

2,760,147

0

0.951

4100

2100

161

1

Rv2458

MmuM

Probable homocysteine S-methyltransferase MmuM (S-methylmethionine:homocysteine methyltransferase) (cysteine methyltransferase)

Disruption provides growth advantage (DeJesus 2017)

Synonymous

2,809,318

0

0.951

4100

2100

161

1

Rv2495c

BkdC

Probable branched-chain keto acid dehydrogenase E2 component BkdC

Arg208Trp

2,812,742

0

0.951

4100

2100

161

1

Rv2498c

CitE

Probable citrate (pro-3S)-lyase (beta subunit) CitE (citrase) (citratase) (citritase) (citridesmolase) (citrase aldolase)

Synonymous

2,817,446

0

0.997

4100

2250

9

8

Rv2502c

AccD1

Probable acetyl-/propionyl-CoA carboxylase (beta subunit) AccD1

Essential in murine spleen (Sassetti and Rubin, 2003)

Phe343Leu

2,912,516

0

0.998

4100

2250

9

3

Rv2585c

Possible conserved lipoprotein

Synonymous

2,927,291

0

0.993

4080

2250

9

21

Rv2598

Conserved hypothetical protein

Disruption provides growth advantage (DeJesus 2017)

Synonymous

2,932,890

0

0.951

4100

2100

161

1

Rv2605c

TesB2

Probable acyl-CoA thioesterase II TesB2 (TEII)

Phe85Leu

2,997,325

0

0.951

4100

2100

161

1

Rv2681

Conserved hypothetical alanine rich protein

Required for growth on cholesterol (Griffin 2011)

Ala196Val

3,032,137

0

0.951

4100

2100

161

1

Rv2720

LexA

Repressor LexA

Val117Ala

3,041,679

0

0.951

4100

2100

161

1

Rv2729c

Probable conserved integral membrane alanine valine and leucine rich protein

Ala266Val

3,042,353

0

0.997

4100

2250

9

8

Rv2729c

Probable conserved integral membrane alanine valine and leucine rich protein

Phe41Leu

3,055,922

0

0.997

4100

2250

9

8

Rv2742c

Conserved hypothetical arginine rich protein

Synonymous

3,140,153

0

0.998

4100

2250

9

4

Rv2833c

UgpB

Probable Sn-glycerol-3-phosphate-binding lipoprotein UgpB

Ser111Ile

3,142,580

0

0.951

4100

2100

161

1

Rv2836c

DinF

Possible DNA-damage-inducible protein F DinF

Pro350Leu

3,152,421

0

0.995

4090

2250

9

13

Rv2845c

ProS

Probable prolyl-tRNA synthetase ProS (proline–tRNA ligase) (PRORS) (global RNA synthesis factor) (proline translase)

Essential in vitro (Minato 2019; DeJesus 2017; Griffin 2011; Sassetti 2003) and in murine spleen (Sassetti and Rubin 2003)

His177Arg

3,157,785

0

0.951

4100

2100

161

1

Rv2849c

CobO

Probable cob(I)alamin adenosyltransferase CobO (corrinoid adenosyltransferase) (corrinoid adotransferase activity)

Trp120Cys

3,158,719

0

0.997

4100

2250

9

8

Rv2850c

Possible magnesium chelatase

Gly446Ser

3,159,237

0

0.951

4100

2100

161

1

Rv2850c

Possible magnesium chelatase

Arg273Gln

3,174,591

0

0.951

4100

2100

161

1

Rv2862c

Conserved hypothetical protein

Arg18Pro

3,189,664

0

0.951

4100

2100

161

1

Rv2879c

Conserved hypothetical protein

Synonymous

3,198,332

0

0.951

4100

2100

161

1

Rv2889c

Tsf

Probable elongation factor Tsf (EF-ts)

In vitro essential (Sassetti 2003; Griffin 2011; DeJesus 2017; Minato 2019)

Thr259Met

3,213,089

0

0.951

4100

2100

161

1

Rv2903c

LepB

Probable signal peptidase I LepB (SPASE I) (leader peptidase I)

In vitro essential (Sassetti 2003; Griffin 2011; DeJesus 2017; Minato 2019)

Asp256Asn

3,223,303

0

0.997

4100

2250

9

8

Rv2914c

PknI

Probable transmembrane serine/threonine-protein kinase I PknI (protein kinase I) (STPK I) (phosphorylase B kinase kinase) (hydroxyalkyl-protein kinase)

Required for growth on cholesterol (Griffin 2011), mutant shows increased growth in THP-1 cells, SCID mice show faster mortality with mutant (Gopalaswamy 2009)

Synonymous

3,235,715

0

0.997

4100

2250

9

8

Rv2922c

Smc

Probable chromosome partition protein Smc

Arg698Gly

3,254,695

0

0.951

4100

2100

161

1

Rv2932

PpsB

Phenolpthiocerol synthesis type-I polyketide synthase PpsB

In vitro essential in CDC1551 (Lamichhane 2003), not in H37Rv (Griffin 2011; DeJesus 2017; Minato 2019)

Synonymous

3,262,628

0

0.951

4100

2100

161

1

Rv2934

PpsD

Phenolpthiocerol synthesis type-I polyketide synthase PpsD

Met127Ile

3,267,715

0

0.951

4100

2100

161

1

Rv2934

PpsD

Phenolpthiocerol synthesis type-I polyketide synthase PpsD

Glu1823Ala

3,282,079

0

0.951

4100

2100

161

1

Rv2940c

Mas

Probable multifunctional mycocerosic acid synthase membrane-associated Mas

Ser213Cys

3,320,554

0

0.951

4100

2100

161

1

Rv2947c

Pks15

Probable polyketide synthase Pks15, involved in the biosynthesis of phenolphthiocerol glycolipids

Synonymous

3,355,417

0

0.997

4100

2250

9

9

Rv2997

Possible alanine rich dehydrogenase

Cys107Ser

3,371,365

0

0.998

4100

2250

9

3

Rv3011c

GatA

Probable glutamyl-tRNA(GLN) amidotransferase (subunit A) GatA (Glu-ADT subunit A)

In vitro essential (Sassetti 2003; Griffin 2011; DeJesus 2017; Minato 2019)

Ala24Thr

3,388,682

0

0.951

4100

2100

161

1

Rv3029c

FixA

Probable electron transfer flavoprotein (beta-subunit) FixA (beta-ETF) (electron transfer flavoprotein small subunit) (ETFSS)

In vitro essential (Sassetti 2003; Griffin 2011), non-essential in rich media (Minato 2019)

Synonymous

3,517,567

0

0.997

4100

2250

9

8

Rv3151

NuoG

Probable NADH dehydrogenase I (chain G) NuoG (NADH-ubiquinone oxidoreductase chain G)

Synonymous

3,534,980

0

0.998

4100

2250

9

3

Rv3166c

Conserved hypothetical protein

Synonymous

3,540,144

0

0.951

4100

2100

161

1

Rv3171c

Hpx

Possible non-heme haloperoxidase Hpx

Thr201Met

3,565,449

0

0.951

4100

2100

161

1

Rv3195

Conserved hypothetical protein

Synonymous

3,594,851

0

0.997

4100

2250

9

8

Rv3218

Conserved protein

Synonymous

3,595,427

0

0.951

4100

2100

161

1

Rv3218

Conserved protein

Synonymous

3,624,710

0

0.951

4100

2100

161

1

Rv3244c

LpqB

Probable conserved lipoprotein LpqB

In vitro essential (Sassetti 2003; Griffin 2011; DeJesus 2017; Minato 2019)

Synonymous

3,664,615

0

0.951

4100

2100

161

1

Rv3282

Conserved hypothetical protein

Ala133Ser

3,678,929

0

0.997

4100

2250

9

8

Rv3296

Lhr

Probable ATP-dependent helicase Lhr (large helicase-related protein)

Val719Met

3,690,854

0

0.951

4100

2100

161

1

Rv3303c

LpdA

NAD(P)H quinone reductase LpdA

Thr29Ala

3,770,588

0

0.951

4100

2100

161

1

Rv3356c

FolD

Probable bifunctional protein FolD: methylenetetrahydrofolate dehydrogenase + methenyltetrahydrofolate cyclohydrolase

In vitro essential (Sassetti 2003; Griffin 2011; DeJesus 2017; Minato 2019)

Gln21Pro

3,857,161

0

0.951

4100

2100

161

1

Rv3437

Possible conserved transmembrane protein

Disruption provides growth advantage (DeJesus 2017)

Leu84Pro

3,877,256

0

0.998

4100

2250

9

3

Rv3456c

RplQ

50S ribosomal protein L17 RplQ

In vitro essential (Minato 2019; Griffin 2011)

Synonymous

3,904,490

0

0.998

4100

2250

9

3

Rv3484

CpsA

Possible conserved protein CpsA

Essential in murine spleen (Sassetti and Rubin, 2003)

Synonymous

3,907,958

0

0.997

4100

2250

9

8

Rv3488

Conserved hypothetical protein

Gly98Arg

3,912,636

0

0.951

4100

2100

162

1

Rv3494c

Mce4F

Mce-family protein Mce4F

Required for growth on cholesterol (Griffin 2011)

Asp245Gly

3,924,350

0

0.951

4100

2100

161

1

Rv3505

FadE27

Probable acyl-CoA dehydrogenase FadE27

Ala218Val

3,977,910

0

0.997

4100

2250

9

8

Rv3538

Probable dehydrogenase. Possible 2-enoyl acyl-CoA hydratase

Synonymous

3,987,645

0

0.997

4100

2250

9

8

Rv3548c

Probable short-chain type dehydrogenase/reductase

Required for growth on cholesterol (Griffin 2011)

Met218Val

4,004,604

0

0.997

4100

2250

9

8

Rv3563

FadE32

Probable acyl-CoA dehydrogenase FadE32

Required for growth on cholesterol (Griffin 2011), essential in murine spleen (Sassetti and Rubin, 2003)

Gln105Arg

4,034,908

0

0.951

4100

2100

161

1

Rv3593

LpqF

Probable conserved lipoprotein LpqF

In vitro essential (Sassetti 2003; Griffin 2011; Minato 2019)

Asn186Ser

4,047,039

0

0.948

4100

2080

172

1

Rv3604c

Probable conserved transmembrane protein rich in alanine and arginine and proline

In vitro essential (Sassetti 2003; Griffin 2011; Minato 2019)

Val153Gly

4,083,511

0

0.951

4100

2100

161

1

Rv3645

Probable conserved transmembrane protein

In vitro essential (DeJesus 2017; Griffin 2011)

Synonymous

4,090,661

0

0.997

4100

2250

9

8

Rv3649

Probable helicase

Essential in murine spleen (Sassetti and Rubin, 2003)

Synonymous

4,157,578

0

0.998

4100

2250

9

3

Rv3712

Possible ligase

In vitro essential (Sassetti 2003; Griffin 2011; DeJesus 2017; Minato 2019)

Gly200Ser

4,171,113

0

0.998

4100

2250

9

3

Rv3725

Possible oxidoreductase

Disruption provides growth advantage (DeJesus 2017)

Synonymous

4,242,970

0

0.951

4100

2100

161

1

Rv3793

EmbC

Integral membrane indolylacetylinositol arabinosyltransferase EmbC (arabinosylindolylacetylinositol synthase)

In vitro essential (Sassetti 2003; Goude 2008; Griffin 2011; DeJesus 2017; Minato 2019)

Synonymous

4,278,968

0

0.951

4100

2100

161

1

Rv3813c

Conserved protein

n/a

Met83Thr