Funding: 
The authors are indebted to the over 30 years of support for the former NIH/NIAID Leprosy Contract to Colorado State University that began in 1979 and ended in 2012.
Resources: 

Appendix

TABLE A1 Functional distribution of M. leprae proteins identified by proteomic analysis and expression of M. tuberculosis orthologs

Sanger IDa

Gene

Protein function

Fraction

M. tuberculosis Sanger IDb

Expression by M. tuberculosis

Identity

Class 0 Virulence, Detoxification, Adaptation

ML0862

ephD

putative oxidoreductase

M

Rv2214c

Pd

80.4%

ML1623c

htpG

heat shock protein Hsp90 family

CW

Rv2299c

P

80.8%

ML2269

bpoC

possible peroxidase BPOC (non-heme-peroxidase)    

C/CW

Rv0554

83.5%

ML2490c

clpB

heat shock protein

CW

Rv0384c

Pd

89.0%

ML2588

yrbE1B

conserved membrane protein

CW

Rv0168

T

85.1%

Class I Lipid Metabolism

ML0134

fadD22

putative acyl-CoA synthetase

M

Rv2948c

T

75.9%

ML0135

pks1

putative polyketide synthase

CW

Rv2946c
Rv2947c

Pd
P/Td

90.5%
82.5%

ML0138c

fadD28

acyl-CoA synthetase    

M/CW

Rv2941

T

81.9%

ML0139

mas

putative mycocerosic synthase   

M/CW

Rv2940c

P/Td

88.0%

ML0323

cysS

putative cysteinyl-tRNA synthase

M/CW

Rv3580c

86.5%

ML0389

choD

putative cholesterol oxidase

CW

Rv3409c

T

88.6%

ML0452c

 

probable alpha-mannosyltransferase PimA

M

Rv2610c

82.3%

ML0726c

bccA

acetyl/propionyl CoA carboxylase [alpha] subunit    

M

Rv3285

Pd

88.7%

ML0731c

accD5

acetyl/propionyl CoA carboxylase [beta] subunit   

M

Rv3280

Pd

88.7%

ML1158

atpA4

probable acetyl-CoA acetyltransferase

C

Rv1323

P/T

86.9%

ML1191c

fas

fatty acid synthase

M/CW

Rv2524c

P/Td

85.8%

ML1229

pks4

type-I polyketide synthase

CW

Rv1180 Rv1181


P/Td

81.3% 75.3%

ML1234c

fadD21

possible acyl-CoA synthase

CW

Rv1185

T

72.4%

ML1657

accD6

acetyl/propionyl CoA carboxylase [beta] subunit

CW

Rv2247

T

92.8%

ML1806cc

inhA

NADH-dependent enoyl-[acyl-carrier-protein] reductase

C/CW

Rv1484

90.3%

ML1996

nrp

probable peptide synthase

CW

Rv0101

Pd

65.7%

ML2349

papA5

possible conserved polyketide synthase associated protein

CW

Rv2939

T

83.8%

ML2353c

ppsE

polyketide synthase   

M/CW

Rv2935

P/Td

82.0%

ML2355c

ppsC

polyketide synthase

M/CW

Rv2933

P/Td

82.3%

ML2358c

fadD26

probable acyl-CoA synthase

CW

Rv2930

P/Td

76.8%

ML2563c

fadE5

acyl-CoA dehydrogenase

C/M

Rv0244c

Pd

89.4%

ML2565

fabG4

possible oxidoreductase   

M/CW

Rv0242c

P/Td

84.8%

ML2655c

fbpC2

secreted antigen 85C   

C

Rv0129c

P

81.3%

Class II Information Pathways

ML0492c

ppiB

putative peptidyl-prolyl cis-trans isomerase B

M

Rv2582

72.5%

ML0548

priA

putative primosomal protein N’ (Replication factor Y)

CW

Rv1402

Pd

80.7%

ML0826

glyS

putative glycyl-tRNA synthase

M

Rv2357c

Pd

90.2%

ML0854

gpsI

putative polyribonucleotide phosphorylase / guanosine pentaphosphate synthetase   

M/CW

Rv2783c

Pd

90.0%

ML0987

recA

recA protein   

C

Rv2737c

P/Td

46.7%

ML1174

rphA

ribonuclease RPHA tRNA (tRNA nucleotidyl transferase)

C

Rv1340

88.8%

ML1381c

polA

DNA polymerase I

M

Rv1629

Pd

85.2%

ML1382

rpsA

30S ribosomal protein S1   

C/M

Rv1630

P/Td

93.8%

ML1498c

typA

possible GTP-binding, protein elongation factor

CW

Rv1165

Pd

85.2%

ML1553

proS

prolyl tRNA synthetase

M/CW

ML1590c

frr

ribosome recycling factor

C

Rv2882c

P/T

90.8%

ML1598c

rpsB

30S ribosomal protein S2   

M

Rv2890c

P/Td

91.5%

ML1659c

rnc

RNAse III

CW

Rv2925c

86.7%

ML1702c

gatA

probable glutamyl-tRNA amidotransferase

C

Rv3011c

88.5%

ML1735c

nrdI

NrdI-family protein

C

Rv3052c

79.7%

ML1844c

rplF

50S ribosomal protein L6

M

Rv0719

Pd

90.5%

ML1847c

rplE

50S ribosomal protein L5   

M/CW

Rv0716

P/Td

91.4%

ML1848c

rplX

50S ribosomal protein L24

CW

Rv0715

P/Td

93.3%

ML1857c

rpsC

30S ribosomal protein S3

M

Rv0707

P/Td

95.0%

ML1860c

rplB

50S ribosomal protein L2

M

Rv0704

P/Td

92.1%

ML1861c

rplW

50S ribosomal protein L23

M

Rv0703

P/Td

85.0%

ML1890cc

rpoC

[beta]’ subunit of RNA polymerase   

C/M/CW

Rv0668

P/Td

95.6%

ML1891cc

rpoB

[beta] subunit of RNA polymerase    

C/M/CW

Rv0667

T

94.9%

ML1906cc

nusG

transcription antitermination protein nusG

C

Rv0639

P

93.4%

ML1956c

rplQ

50S ribosomal protein L17

M

Rv3456c

Pd

89.9%

ML1959c

rpsK

30S ribosomal protein S11

CW

Rv3459c

T

81.9%

ML2393

greA

probable transcriptional elongation factor

C

Rv1080c

Pd

94.5%

ML2684c

ssb

single strand binding protein   

C

Rv0054

P

89.3%

Class III Cell Wall and Cell Processes

ML0042

 

putative conserved membrane protein

CW

Rv3882c

Pd

72.1%

ML0047c

 

putative conserved transmembrane protein

CW

Rv3877

74.0%

ML0092

glf

putative UDP-galactopyranose mutase

CW

Rv3809c

Pd

86.6%

ML0093

glfT

bifunctional UDP-galactofuranosyl transferase

M

Rv3808c

P/Td

85.4%

ML0096

 

putative conserved transmembrane protein

M/CW

Rv3805

80.9%

ML0105c

embA

putative arabinosyl transferase

CW

Rv3794

Pd

64.2%

ML0136

llpX

putative conserved lipoprotein

M/CW

Rv2945c

P/T

76.4%

ML0203

 

putative conserved transmembrane protein

CW

Rv3635

77.2%

ML0227

 

hypothetical protein

C

Rv3605c

85.4%

ML0319c

lpqE

putative lipoprotein

CW

Rv3584

P

63.4%

ML0488c

secF

putative protein-export membrane protein

M

Rv2586c

72.1%

ML0557c

lprG

putative lipoprotein   

M/CW

Rv1411c

P/Td

68.1%

ML0569c

 

possible conserved exported protein

M

Rv1433

68.3%

ML0595

 

probable conserved ATP-binding protein ABC transporter

C

Rv1463

P

85.8%

ML0644c

 

putative integral membrane protein   

M/CW

Rv3193c

P

86.1%

ML0691c

dacB1

putative D-alanyl-D-alanine carboxypeptidase

M

Rv3330

77.2%

ML0779c

secA

putative preprotein translocase subunit

CW

Rv3240c

Pd

87.5%

ML0810c

 

possible secreted protein

CW

Rv3212

P/Td

79.9%

ML0857c

 

putative conserved transmembrane protein

CW

Rv2219

80.8%

ML0910

murF

UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanyl ligase (D-alanine:D-alanine-adding enzyme)

CW

Rv2175c

75.5%

ML0977c

ftsK

cell division transmembrane protein

CW

Rv2748c

Pd

78.1%

ML1248

 

probable macrolide ABC-transporter protein, ATP binding component

CW

Rv2477c

Pd

92.3%

ML1334c

 

possible conserved membrane protein

CW

Rv2091c

T

62.9%

ML1425c

 

probable sugar ABC-transport integral membrane protein

M

Rv2039c

79.2%

ML1562c

efpA

putative transmembrane efflux protein

CW

Rv2846c

T

86.5%

ML1622

ffh

signal recognition particle protein

M

Rv2916c

Pd

87.8%

ML1633cc

 

probable exported protease

M

Rv2224c

P/Td

84.8%

ML1667c

 

possible conserved membrane or secreted protein

M

Rv2969c

P

65.5%

ML1769

uspB

probable sugar ABC transporter integral membrane protein

C

Rv2317

85.0%

ML1808c

 

possible conserved membrane protein

M

Rv1481

P

91.0%

ML1839c

sppA

protease IV, signal peptide peptidase

M

Rv0724

P

80.2%

ML2095c

psts3

periplasmic phosphate-binding lipoprotein

M

Rv0928

P

77.3%

ML2296

 

putative conserved transmembrane protein

M

Rv3669

77.9%

ML2305

 

probable anion transporter ATPase

M

Rv3679

T

84.2%

ML2378

mmpL4

conserved large transmembrane protein

CW

Rv0450c

T

78.4%

ML2410c

 

conserved transmembrane protein.

CW

Rv0528

80.9%

ML2433

 

conserved membrane protein

M

Rv0497

54.2%

ML2454c

hbhA

possible hemagglutinin   

C/M/CW

Rv0475

P/Td

81.4%

ML2687c

 

conserved transmembrane protein

CW

Rv0051

78.7%

Classe VII Intermediary Metabolism and Respiration

ML0065

ethA

putative monooxygenase

CW

Rv3854

P/Td

80.1%

ML0074

glpQ1

putative glycerophosphoryl diester phosphodiesterase

CW

Rv3842c

T

88.8%

ML0108c

 

putative oxidoreductase

M

Rv3791

89.0%

ML0109c

 

putative FAD-linked oxidoreductase

CW

Rv3790

Pd

86.6%

ML0127c

 

possible methyltransferase

M/CW

Rv2959c

76.1%

ML0150c

pgi

glucose-6-phosphate isomerase

CW

Rv0946c

85.5%

ML0155

sucC

succinyl-CoA synthase [beta]

CW

Rv0951

Pd

86.7%

ML0161

purH

putative phosphoribosylamino-imidazolecarboxamide formyl-transferase/IMP cyclohydrolase

M

Rv0957

88.1%

ML0183

moeA1

putative molybdopterin biosynthesis protein

CW

Rv0994

Pd

88.3%

ML0210cc

ppa

putative inorganic pyrophosphatase

M

Rv3628

Pd

89.5%

ML0235

clpC

putative ATP-dependent Clp protease ATP-binding subunit ClpC

M/CW

Rv3596c

Pd

97.2%

ML0255

eno

putative enolase   

M

Rv1023

P

88.8%

ML0269c

fgd1

putative F-420-dependent glucose-6-phosphate dehydrogenase

C

Rv0407

P

89.3%

ML0297cc

thiG

putative thiamine biosynthesis protein

CW

Rv0417

86.8%

ML0348

 

possible coenzyme F420-dependent oxidoreductase   

C/M

Rv3520c

86.8%

ML0365

rpsI

30S ribosomal protein S9

M

Rv3442c

83.2%

ML0379

gcp

probable O-sialoglycoprotein endopeptidase

C

Rv3419c

86.1%

ML0388

guaB3

putative inosine-5’-monophosphate dehydrogenase   

C/M

Rv3410c

90.5%

ML0393c

 

probable hydrolase

C

Rv3400

P

74.4%

ML0418

 

putative oxidoreductase

CW

Rv3368c

81.9%

ML0429c

 

probable short-chain type dehydrogenase/reductase

C

Rv2509

Pd

88.8%

ML0485c

gabT

putative 4-aminobutyrate aminotransferase

CW

Rv2589

83.7%

ML0521

pepQ

putative cytoplasmic peptidase  PepQ

C

Rv2535c

83.0%

ML0537

pyrF

orotidine 5’-phosphate decarboxylase

CW

Rv1385

77.3%

ML0544

metK

putative S-adenosylmethionine synthase   

C/M

Rv1392

P/Td

91.3%

ML0551

 

putative methyltransferase

C

Rv1405c

77.7%

ML0559

ribA

putative GTP cyclohydrolase II/3,4-dihydroxy-2-butanone-4-phosphate synthase

M

Rv1415

P

93.4%

ML0570

gap

glyceraldehyde 3-phosphate dehydrogenase    

M

Rv1436

Pd

89.1%

ML0572

tpi

triosephosphate isomerase

C

Rv1438

Pd

83.9%

ML0674c

folD

putative methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase

C

Rv3356c

P

86.5%

ML0685c

 

putative hydrolase

M

Rv3337 Rv3338

–                –

74.6%
65.9%

ML0763

pmmA

putative phosphomannomutase

CW

Rv3257c

83.1%

ML0839c

cysK

putative cysteine synthase   

C/M

Rv2334

P

85.8%

ML0861c

sucB

putative dihydrolipoamide acyltransferase

C

Rv2215

Pd

81.8%

ML0873

adk

putative adenosine kinase   

C

Rv2202c

83.3%

ML0925

glnA

glutamine synthase class I    

M

Rv2220

Pd

91.8%

ML0961c

metE

5-methyltetrahydropteroyltriglutamate-homocystein methyltransferase    

C/CW

Rv1133c

Pd

85.0%

ML0985

 

possible glycosyltransferase

CW

Rv2739c

80.9%

ML0995

miaA

tRNA [delta](2)-isopentenyl-pyrophosphate transferase

CW

Rv2727c

82.2%

ML1059

dapE

succinyl-diaminopimelate desuccinylase

M

Rv1202

86.7%

ML1091

mdh

probable malate dehydrogenase

C

Rv1240

Pd

89.1%

ML1095c

odhA/ sucA

2-oxoglutarate dehydrogenase, E1 components

M

Rv1248c

Pd

89.0%

ML1129

hom

homoserine dehydrogenase   

M

Rv1294

99.8%

ML1142

atpH

bi-domained ATP synthase B, [delta] chain protein    

M

Rv1307

P/Td

77.8%

ML1143

atpA

ATP synthase [alpha] chain     

C

Rv1308

P/Td

69.0%

ML1144

atpG

ATP synthase [gamma] chain     

M/CW

Rv1309

P/Td

83.9%

ML1145

atpD

ATP synthase [beta] chain   

C/M

Rv1310

P/Td

92.6%

ML1167

 

possible hydrolase

M

Rv1333

76.7%

ML1257

hisD

histidinol dehydrogenase

CW

Rv1599

84.8%

ML1307c

metH

probable 5-methyltetrahydrofolate-homocystein methyltransferase metH (methionine synthase, vitamin-B12 dependent isozyme)

C

Rv2124c

Pd

88.3%

ML1340c

ribD

possible bifunctional enzyme riboflavin biosynthesis protein RibD + 5-amino-6-uracil reductase

C

Rv2671

Pd

72.9%

ML1469c

ndk

nucleoside diphosphate kinase NDK

C

Rv2445c

P

87.4%

ML1480

clpP

ATP-dependent Clp protease proteolytic subunit

C

Rv2461c

95.0%

ML1513c

dapA

probable dihydrodipicolinate synthase DAPA (DHDPS)

C

Rv2753c

86.7%

ML1669

 

probable oxidoreductase

C

Rv2971

P

79.8%

ML1685c

leuC

3-isopropylmalate dehydratase large subunit

CW

Rv2988c

P/Td

88.7%

ML1691c

leuB

3-isopropylmalate dehydrogenase

M

Rv2995c

T

83.9%

ML1694c

ilvC

ketol-acid reductoisomerase  IlvC

C

Rv3001c

P/Td

86.2%

ML1696c

ilvB

probable acetolactate syntase  (large subunit) IlvB

C

Rv3003c

P

87.1%

ML1712c

fixA

probable electron transfer flavoprotein (beta subunit) FixA

C

Rv3029c

Pd

95.1%

ML1730

adhA

alcohol dehydrogenase

CW

Rv3045

Pd

85.8%

ML1832c

kad

probable adenylate kinase Kad

C

Rv0733

P

83.4%

ML1942

 

probable cholesterol dehydrogenase

CW

Rv1106c

P

75.5%

ML1950cc

 

carbohydrate degrading enzyme

M

Rv1096

81.3%

ML1985cc

aceA

isocitrate lyase   

M/CW

Rv1916

T

87.9%

ML2011

aao

probable D-amino acido oxidase AAO   

C

Rv1905c

71.4%

ML2046

lldD2

L-lactate dehydrogenase

M

Rv1872c

P/Td

85.0%

ML2088c

 

putative cytochrome P450   

C/M

Rv1880c

38.0%

ML2130c

gltA2

citrate synthase  GLTA2

C/M

Rv0896

P

91.0%

ML2226c

ptrB

protease II

CW

Rv0781 Rv0782


69.9% 77.8%

ML2227c

purC

phosphoribosylaminoimidazole-succinocarboxamide synthase

M

Rv0780

81.5%

ML2322c

asd

aspartate semialdehyde dehydrogenase

M

Rv3708c

84.4%

ML2324

leuA

probable 4-dihydroxy-2-naphthoate octaprenyltransferase 2-isopropylmalate synthase

CW

Rv3710

P

80.6%

ML2387c

lpd

dihydrolipoamide dehydrogenase Lpd

M

Rv0462

P

83.1%

ML2394c

metB

cystathionine [gamma]-synthase

M

Rv1079

P

87.3%

ML2396c

cysM2

probable cystathionine [beta]-synthase CBS

C

Rv1077

P

90.1%

ML2406c

menA

UDP-galactose 4-epimerase

CW

Rv0534c

80.6%

ML2419c

hemB

hemB, [delta]-aminolevulinic acid dehydratase

CW

Rv0512

87.5%

ML2428c

galE2

probable UDP-galactose 4-epimerase GALE2

C

Rv0501

P

84.0%

ML2430c

proC

pyrroline-5-carboxylate reductase

M/CW

Rv0500

82.4%

ML2441cc

gpm

phosphoglycerate mutase   

C

Rv0489

89.0%

ML2449c

 

putative amidohydrolase

CW

Rv0480c

P

81.9%

ML2474

 

possible   cytidine/deoxycytidylate deaminase

CW

Rv3752c

87.4%

ML2501c

 

probable iron-sulphur-binding reductase

CW

Rv0338c

P

78.1%

ML2573

gabD

probable succinate-semialdehyde dehydrogenase [NADP+] dependent

C

Rv0234c

P

82.9%

ML2659cc

pepA

probable secreted serine protease

M

Rv0125

T

70.1%

ML2672c

icd2

probable isocitrate dehydrogenase [NADP+]

M

Rv0066c

P

85.4%

Class VIII Hypothetical Unknown

ML0959

 

hypothetical protein

CW

Class IX – Regulatory Proteins

ML0639c

whiB7

putative transcriptional regulator

CW

Rv3197A

P

69.3%

ML1286

 

possible two-component response regulatory protein   

CW

Rv1626

P

90.7%

ML1511

npdA

probable NAD-dependent deacetylase NpdA

M

Rv1151c

85.2%

ML2302

 

putative Crp/Fnr-family transcriptional regulator   

C/M/CW

Rv3676

P

96.0%

ML2440c

senX3

probable two-component system sensor histidine kinase

M

Rv0490

P

84.0%

Class X – Conserved Hypotheticals

ML0129c

 

conserved hypothetical protein

M

Rv2953

P/T

86.6%

ML0333c

 

conserved hypothetical protein

C

ML0369c

 

conserved hypothetical protein

CW

ML0405

 

conserved hypothetical protein

M

Rv3616c

T

62.7%

ML0447

 

conserved hypothetical protein

M/CW

ML0593

 

conserved hypothetical protein

M

Rv1461

P

54.3%

ML0703

 

conserved hypothetical protein   

M

Rv3311

77.5%

ML0781

 

conserved hypothetical protein

C

Rv3237c

T

80.6%

ML0901

 

conserved hypothetical protein

CW

Rv2172c

T

80.9%

ML1040

 

conserved hypothetical protein

M

Rv2681

P

77.4%

ML1330

 

conserved hypothetical protein

CW

Rv2095c

74.2%

ML1368

 

conserved hypothetical protein

CW

Rv1709

78.9%

ML1369

 

conserved hypothetical protein

M/CW

Rv1710

77.9%

ML1380

 

conserved hypothetical protein

M/CW

Rv1780

P

82.4%

ML1418c

 

conserved hypothetical protein    

C/CW

Rv1732c

P

86.3%

ML1423c

 

conserved hypothetical protein    

M

Rv2037

P/T

80.5%

ML1444

 

conserved hypothetical protein    

M

Rv2054

P

76.1%

ML1637c

 

conserved hypothetical protein    

CW

Rv2228c

76.8%

ML1661c

 

conserved hypothetical protein    

CW

Rv2927c

90.2%

ML1704

 

conserved hypothetical protein   

CW

Rv3013

84.3%

ML1706c

 

conserved hypothetical protein   

C

Rv3015c

78.3%

ML1782c

 

conserved hypothetical protein   

CW

Rv2257c

76.4%

ML2031

 

conserved hypothetical protein   

CW

Rv1883c

76.2%

ML2070

 

conserved hypothetical protein   

M

Rv1836c

P

66.0%

ML2113c

 

conserved hypothetical protein   

CW

Rv0910c

83.9%

ML2336

 

conserved hypothetical protein   

CW

Rv3722c

T

87.6%

ML2465

 

conserved hypothetical protein   

M

Rv0464c

P/T

67.4%

ML2491

 

conserved hypothetical protein   

M/CW

Rv1754c

P

61.5%

ML2627

 

conserved hypothetical protein   

CW

Rv0216

P

35.8%

ML2640c

 

conserved hypothetical protein   

CW

Rv0146

P

78.1%

a Functional classification and ID refer to the original annotated M. leprae gene number assigned by Sanger ID from Cole ST et al. 2001. Nature 409:1007–1011.

b M. tuberculosis gene number refers to H37Rv Sanger ID from Cole ST et al. 1998. Nature 393:537–544.

c Proteins also shown to be expressed by transcriptional analysis.

d Proteins identified by subcellular protein profiling from Mawuenyega KG et al. 2005. Mol Biol Cell 16:396–404.

C – cytosolic/soluble; M – membrane; CW – cell wall; T – gene expression demonstrated by transcriptional analysis; P – gene expression demonstrated by proteomic analysis.

eradication
ROM
BL
BT
LL
BB
TT
PB
MB
RR
BI