Supplemental Material Carbohydrate utilization

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Q. Glycine degradation

Gene	H. somnus 129Pt	H. ducreyi 35000HP	H. influenzae Rd
gcv system
*gcvP* glycine dehydrogenase (decarboxylating) 1.4.4.2	no	no	no
*lpdA* dihydrolipoate dehydrogenase	HS_1093	HD1623	HI1231
*gcvH* lipoyl protein	no	no	no
*gcvT* aminomethyltransferase 2.1.2.10	no	no	no

R. Serine degradation

Gene	H. somnus 129Pt	H. ducreyi 35000HP	H. influenzae Rd
L-serine to pyruvate
*sdaB* L-serine deaminase 2 4.3.1.17	no	HD1142	HI0288
*sdaA* L-serine deaminase 1	no	no	no
*sdhY* L-serine deaminase 3	no	no	no

S. Alanine degradation

Gene	H. somnus 129Pt	H. ducreyi 35000HP	H. influenzae Rd
L-alanine to pyruvate
alanine dehydrogenase 1.4.1.1	HS_0232	HD1663	HI1362

T. Proline degradation

Gene	H. somnus 129Pt	H. ducreyi 35000HP	H. influenzae Rd
L-proline to L-glutamate
putA proline dehydrogenase 1.5.99.8/Delta-1-pyrroline-5-carboxylate dehydrogenase 1.5.1.12	no	no	no

U. Phenylalanine degradation

Gene	H. somnus 129Pt	H. ducreyi 35000HP	H. influenzae Rd
L-phenylalanine to L-tyrosine
phhA phenylalanine-4-hydroxylase 1.14.16.1	no	no	no

V. Tyrosine degradation

Gene	H. somnus 129Pt	H. ducreyi 35000HP	H. influenzae Rd
phhC/tyrB tyrosine aminotransferase 2.6.1.5	no	no	no
*hppD* 4-hydroxyphenylpyruvate dioxygenase 1.13.11.27	no	no	no

W.Tryptophan degradation

Gene	H. somnus 129Pt	H. ducreyi 35000HP	H. influenzae Rd
L-tryptophan to pyruvate
tnaA tryptophanase	HS_0801	no	no
L-tryptophan to tryptamine
aromatic L-amino acid decarboxylase	no	no	no
L-tryptophan to indole-3-acetate
key enzyme: indolepyruvate carboxylase	no	no	no
L-tryptophan to anthranilate
tryptophan 2,3-dioxygenase 1.13.11.11	no	no	no

Table S7. Nucleotide metabolism

Gene	H. somnus 129Pt	H. ducreyi 35000HP	H. influenzae Rd
purA adenylosuccinate synthetase	HS_1328	HD1807	HI1633
purB adenylosuccinate lyase	HS_1593	HD1649	HI0639
purC phosphoribosylaminoimidazole-succinocarboxamide synthase (SAICAR synthetase)	HS_1364	HD0251N-terminal HD0252 C-terminal	HI1726
purD phosphoribosylamine--glycine ligase	HS_1626	HD1042 C-terminal HD1043 N-terminal	HI0888
purE phosphoribosylaminoimidazole carboxylase (AIR carboxylase)	HS_0672	HD1424	HI1615
purF amidophosphoribosyltransferase	HS_0916	HD1210 C-terminal HD1209 N-terminal	HI1207
purH phosphoribosylaminoimidazolecarboxamide formyltransferase	HS_1625	HD1703 N-terminal HD1702 N-terminal	HI0887
purK phosphoribosylaminoimidazole carboxylase, ATPase subunit	HS_0839	HD1421 C-terminal HD1423 N-terminal	HI1616
purL phosphoribosylformylglycinamidine synthase	HS_1503	HD2008 N-terminal HD2009 central region HD2010 C-terminal	HI0752
purM phosphoribosylformylglycinamidine cyclo-ligase	HS_1551	HD0561	HI1429
purN phosphoribosylglycinamide formyltransferase	HS_0913	HD0548	HI1428
purR purine nucleotide synthesis repressor	HS_1032	HD1641	HI1635
purT phosphoribosylglycinamide formyltransferase 2	HS_0549	HD0548	no – but this enzyme is redundant with purN
purU formyltetrahydrofolate deformylase	HS_0786	no	HI1588
guaA GMP synthase, glutamine-hydrolyzing (glutamine amidotransferase)	HS_0421	HD1504	HI0222
guaB IMP dehydrogenase (inosine-5'-monophosphate dehydrogenase)	HS_0420	HD1503	HI0221
guaC GMP reductase [Escherichia coli]	no	no	no
adk adenylate kinase	HS_0648	HD0826	HI0349
gmk guanylate kinase	HS_1457	HD1830	HI1743
ndk nucleoside-diphosphate kinase	HS_0387	HD1053	HI0876
nrdA ribonucleoside diphosphate reductase 1, alpha subunit	HS_1196	HD1731	HI1659
nrdB ribonucleoside-diphosphate reductase 1, beta subunit	HS_0961	HD1732	HI1660
nrdE ribonucleoside-diphosphate reductase 2, alpha subunit	no	no	no
nrdF ribonucleoside-diphosphate reductase 2, beta subunit	no	no	no
carA/pyrA carbamoyl phosphate synthetase, glutamine amidotransferase small subunit	no	HD0235	no
carB carbamoyl phosphate synthase, large subunit	no	HD0233	no
pyrB aspartate carbamoyltransferase, catalytic subunit	no	no	no
pyrC dihydro-orotase	no	no	no
pyrD dihydroorotate dehydrogenase	no	HD1626	HI1401
pyrE orotate phosphoribosyltransferase	no	HD1759	HI0272
pyrF orotidine 5`-phosphate decarboxylase	no	HD1356	HI1224
pyrG CTP synthase (UTP--ammonia ligase)	HS_0552	HD0373	HI1077
pyrH uridylate kinase	HS_0987	HD1597	HI1065
pyrI aspartate carbamoyltransferase, regulatory subunit	no	no	no
pyrR pyrimidine operon regulatory protein / uracil phosphoribosyltransferase	HS_1561	HD1178 HD1181	HI0459

Table S8. Genes involved in TCA cycle, Embden-Meyerhof, pentose phosphate, Entner-Doudoroff, ubiquinone/menaquinone biosynthesis and fermentation pathways in H. somnus 129Pt, H. ducreyi 35000HP and H. influenzae Rd.

TCA cycle	H. somnus 129Pt	H. ducreyi 35000HP	H. influenzae Rd
aceE pyruvate dehydrogenase E1 component	HS_1095	HD1625	HI1233
aceF pyruvate dehydrogenase, E2 complex	HS_1094	HD1624	HI1232
lpdA pyruvate dehydrogenase multienzyme complex, E3	HS_1093	HD1623	HI1231
gltA citrate synthase	HS_0960	no	no
acnA aconitase	no	no	no
acnB aconitate hydratase2	HS_1270	no	no
icd isocitrate dehydrogenase	no	no	no
sucA alpha ketoglutarate dehydrogenase	HS_0959	HD1336	HI1662
sucB alpha ketoglutarate dehydrogenase, dihydrolipoamide succinyltransferase component	HS_0958	HD1334	HI1661
sucC succinyl-CoA synthetase beta chain	HS_0957	no	HI1196
sucD succinyl-CoA synthetase alpha chain	HS_0956	no	HI1197
sdhA succinate dehydrogenase flavoprotein subunit	no	no	no
sdhB succinate dehydrogenase iron-sulfur protein	no	no	no
sdhC succinate dehydrogenase cytochrome b-556 subunit	no	no	no
sdhD succinate dehydrogenase hydrophobic membrane anchor protei	no	no	no
fumA fumarase	no	no	no
fumB fumarate hydratase class I, anaerobic	no	no	no
fumC fumarate hydratase class II	HS_1102	HD1986	HI1398
mdh malate dehydrogenase	HS_1055	HD0264	HI1210
malate dehydrogenase, FAD/NAD(P)-binding domain	no	HD0165	no
frdA fumarate reductase, flavoprotein subunit	HS_1277	HD0030	HI0835
frdB fumarate reductase, iron-sulfur protein	HS_1278	HD0032	HI0834
frdC fumarate reductase 15 kDa hydrophobic protein	HS_1279	HD0033	HI0833
frdD fumarate reductase, 13 kDa hydrophobic protein	HS_1280	HD0034	HI0832
Embden-Meyerhof
glk hexokinase (glucokinase)	HS_0379	no		no
putative glucokinase from Streptomyces coelicolor A3 NP_624417	no	no		HI0144
glucokinase from Streptomyces coelicolor A3 NP_626383	HS_1041 ROK	no		HI0182
pfkA 6-phosphofructokinase I	HS_0485	HD0465		HI0982
pfkB 6-phosphofructokinase II	no	no		no
fruK 1-phosphofructokinase	no	no		HI0447
fba fructose bisphosphate aldolase	HS_0206	HD0864		HI0524
pgi glucose 6-phosphate isomerase	HS_0938	HD0418		HI1576
tpiA triosephosphate isomerase	HS_1591	HD0762		HI0678
gap glyceraldehyde 3-phosphate dehydrogenase	HS_1466	HD1291		HI0001
pgk phosphoglycerate kinase	HS_0207	HD0865		HI0525
gpmA phosphoglycerate mutase 1	HS_1445	HD1659		HI0757
gpmB phosphoglycerate mutase 2	HS_1664	no		no
eno enolase	HS_0561	HD0477		HI0932
pyk pyruvate kinase II	HS_1086	HD0446		HI1573
ldhA fermentative D-lactate dehydrogenase, NAD-dependent	no	no		HI0085
dld D-lactate dehydrogenase, FAD protein, NADH independent	HS_0784	no		HI1649
lldD/lctD L-lactate dehydrogenase	no	HD0084		HI1739.1
ptsG PTS system, glucose-specific IIABC component	no	no		no
crr PTS system, glucose-specific enzyme II, A component	HS_1096	HD0227		HI1711
Pentose Phosphate
zwf glucose 6-phosphate 1-dehydrogenase	HS_1651	HD0838		HI0558
pgl 6-phosphogluconolactonase	HS_1652	HD0836		HI0556
gnd 6-phosphogluconate dehydrogenase, decarboxylating	HS_1654	HD0833		HI0553
rpiA ribose 5-phosphate isomerase A, constitutive	HS_0123	HD0199		HI0464
rpiB ribose 5-phosphate isomerase B, inducible	no	no		no
rpe ribulose phosphate 3-epimerase	HS_0175 HS_0057	HD1929		HI0566
tktA transketolase I	HS_0551	HD1723		HI1023
tktB transketolase II	no	no		no
talA transaldolase A	no	no		no
talB transaldolase B	HS_0204	HD0310		HI1125
Entner-Doudoroff
edd phosphogluconate dehydratase	HS_0342	no		HI0738
eda oxaloacetate decarboxylase	HS_1603	no		HI0047
Ubiquinone biosynthesis
ubiA 4-hydroxybenzoate-octaprenyltransferase	HS_0159	HD1647		no
ubiB NADPH:flavin oxidoreductase	HS_0544	HD0717		no
ubiC chorismate lyase	HS_0150	no		no
ubiD 3-octaprenyl-4-hydroxybenzoate carboxy-lyase	HS_0474	HD0197		no
ubiE ubiquinone/menaquinone biosynthesis methyltransferase	HS_0542	HD0719		no
ubiH 2-octaprenyl-6-methoxyphenol hydroxylase	HS_0681	HD0579		no
ubiX 3-octaprenyl-4-hydroxybenzoate carboxy-lyase	HS_0915	HD1360		no
ubiG 3-demethylubiquinone 3-methyltransferase / 2-octaprenyl-6-hydroxyphenol methylase	HS_1162	HD1750		no
ubiF 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone hydroxylase	HS_1156	HD1874		no
menaquinone biosynthesis
menA 1,4-dihydroxy-2-naphthoate octaprenyltransferase	HS_0221	HD0683		HI0509
menB dihydroxynaphthoic acid synthase	HS_0562	HD1925		HI0968
menC o-succinylbenzoate-CoA synthase (OSB synthase)	HS_0563	HD1055		HI0969
menD 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase	HS_0617	HD1853		HI0283
menE O-succinylbenzoate-CoA synthase	HS_1207	HD1271		HI0194
menF menaquinone-specific isochorismate	HS_0618	HD0621		HI0285
entC isochorismate synthase, enterobactin specific	no	no		no
menG S-adenosylmethionine:2-demethylmenaquinone methyltransferase	HS_0220	HD0166		HI0508
chorismate biosynthesis (shikimate pathway)
aroA 3-phosphoshikimate-1-carboxyvinyltransferase	HS_0613	HD1383		HI1589
aroB 3-dehydroquinate synthase	HS_1114	HD0422		HI0208
aroC 3-dehydroquinate dehydratase (chorismate synthase)	HS_1205	HD1274		HI0196
aroD 3-dehydroquinate dehydratase	no	no		no
aroE 5-enolpyruvoylshikimate-3-phosphate synthase	HS_0006	HD0415		HI0655 HI0607
aroF 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (DAHP synthetase)/ chorismate synthase	no	HD0444		no
aroG 2-dehydro-3-deoxyphosphoheptonate aldolase// 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (DAHP synthetase, phenylalanine repressible)	HS_0941	HD1475		HI1547
aroH 2-dehydro-3-deoxyphosphoheptonate aldolase	no	no		no
aroK shikimate kinase I	HS_1113	HD0423		HI0207
aroL shikimate kinase II	no	no		no
Fermentation
pyruvate to D-lactate
ldhA D-lactate dehydrogenase	HS_0945	no		HI0085
dld D-lactate dehydrogenase	HS_0784	no		HI1649
pyruvate to L-lactate
lldD L-lactate dehydrogenase	no	HD0084		HI1739.1
pyruvate to formate and acetyl-CoA
pflB formate acetyltransferase 1	HS_1136	HD0990		HI0180
acetyl-CoA to acetate
pta phosphate acetyltransferase	HS_0802	HD1457		HI1203
ackA acetate kinase A	HS_0803	HD1456		HI1204
acetyl-CoA to ethanol
adhE acetaldehyde/alcohol dehydrogenase	no	no		no

Table S9. NAD biosynthesis and salvage

A. de novo pathway

Gene

H. somnus 129Pt

H. ducreyi 35000HP

H. influenzae Rd

nadA

quinolinate synthetease A

no

no

no

nadB
L-aspartate oxidase

no

no

no

nadC
quinolinate phosphoribosyl transferase

no

no

no

nadD
NAMN adenylyltransferase

no

no

no

nadE
NAD synthetase, prefers NH3 over glutamine

no

no

no

B. salvage pathway (from MetaCyc (8))

Gene	H. somnus 129Pt	H. ducreyi 35000HP	H. influenzae Rd
NAD salvage pathway II
nadR bifunctional protein: NMN adenylyltransferase; ribosylnicotinamide kinase	HS_0087	HD0274 C-terminal fragment HD0275 N-terminal fragment	HI0763
NAD salvage pathway I
NAD(+) nucleosidase 3.2.2.5	no	no	no
nudC NADH pyrophosphatase	no	no	possibly HI0432 conserved hypothetical protein 47% aa identity
pncA nicotinamidase and pyrazinamidase	no	no	no
pncB nicotinate phosphoribosyltransferase	no	no	no

Directory: content -> suppl
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suppl -> Additional file 5, Table costs and ccdss process-related outcomes for trials of acute care management a
suppl -> Supplementary Notes and Figures

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