Supplemental Table S3. Genes Downregulated by Daptomycin and Their Response Status With

Supplemental Table S3. Genes downregulated by daptomycin and their response status with other antibiotics

Locus Gene Fold Valuea,b Gene-Protein Name Sub Category ID Symbol Dapc Vanc Oxac CCCPc Nisc KVRd

Amino acid biosynthesis

SA1977 pheA prephenate dehydratase Aromatic amino acid family -1.59 0.00 0.00 0.00 0.00 0.00 SA0168 argJ glutamate N- Glutamate family -1.85 0.00 0.00 0.00 0.00 0.00 acetyltransferase/amino-acid acetyltransferase Cell envelope

SA0193 NA maltose ABC transporter, maltose- Other -2.68 -3.66 0.00 -1.81 -5.93 0.00 binding protein, putative SA1045 NA iron compound ABC transporter, Other -2.11 0.00 0.00 0.00 0.00 0.00 iron compound-binding protein SA2167 NA iron compound ABC transporter, Other -1.63 0.00 -1.98 2.29 0.00 0.00 iron compound-binding protein SA1062 atl bifunctional autolysin Biosynthesis and degradation of surface -3.10 -2.16 -3.07 -7.06 0.00 2.28 polysaccharides and lipopolysaccharides SA2298 NA N-acetylmuramoyl-L-alanine Biosynthesis and degradation of surface -2.34 0.00 -1.95 -3.47 0.00 2.25 amidase, family 4 polysaccharides and lipopolysaccharides SA0145 cap5J capsular polysaccharide Biosynthesis and degradation of surface -2.29 0.00 0.00 0.00 0.00 0.00 biosynthesis protein Cap5J polysaccharides and lipopolysaccharides SA0938 dltD DltD protein Biosynthesis and degradation of surface -2.04 -2.20 -1.80 -5.25 0.00 0.00 polysaccharides and lipopolysaccharides SA0146 cap5K capsular polysaccharide Biosynthesis and degradation of surface -1.95 0.00 0.00 0.00 0.00 0.00 biosynthesis protein Cap5K polysaccharides and lipopolysaccharides SA0149 cap5N capsular polysaccharide Biosynthesis and degradation of surface -1.94 0.00 -2.02 0.00 0.00 0.00 biosynthesis protein Cap5N polysaccharides and lipopolysaccharides SA0142 cap5G UDP-N-acetylglucosamine 2- Biosynthesis and degradation of surface -1.93 0.00 0.00 0.00 0.00 0.00 epimerase Cap5G polysaccharides and lipopolysaccharides SA0140 cap5E capsular polysaccharide Biosynthesis and degradation of surface -1.92 0.00 0.00 0.00 0.00 0.00 biosynthesis protein Cap5E polysaccharides and lipopolysaccharides 2

SA0148 cap5M capsular polysaccharide Biosynthesis and degradation of surface -1.90 0.00 -1.58 0.00 0.00 0.00 biosynthesis galactosyltransferase polysaccharides and lipopolysaccharides Cap5M SA0138 cap5C capsular polysaccharide Biosynthesis and degradation of surface -1.88 0.00 -1.52 2.01 0.00 0.00 biosynthesis protein Cap5C polysaccharides and lipopolysaccharides SA0151 cap5P UDP-N-acetylglucosamine 2- Biosynthesis and degradation of surface -1.86 0.00 0.00 0.00 0.00 0.00 epimerase Cap5P polysaccharides and lipopolysaccharides SA0936 dltB DltB protein Biosynthesis and degradation of surface -1.77 0.00 -2.04 -8.60 -2.25 2.87 polysaccharides and lipopolysaccharides SA0141 cap5F capsular polysaccharide Biosynthesis and degradation of surface -1.70 0.00 0.00 -1.53 0.00 0.00 biosynthesis protein Cap5F polysaccharides and lipopolysaccharides SA0147 cap5L capsular polysaccharide Biosynthesis and degradation of surface -1.63 0.00 0.00 -1.90 0.00 0.00 biosynthesis protein Cap5L polysaccharides and lipopolysaccharides SA0137 cap5B capsular polysaccharide Biosynthesis and degradation of surface -1.61 0.00 -2.01 1.58 0.00 0.00 biosynthesis protein Cap5B polysaccharides and lipopolysaccharides SA0143 cap5H capsular polysaccharide Biosynthesis and degradation of surface -1.59 0.00 0.00 0.00 0.00 0.00 biosynthesis protein Cap5H polysaccharides and lipopolysaccharides SA0150 cap5O capsular polysaccharide Biosynthesis and degradation of surface -1.53 0.00 0.00 0.00 0.00 0.00 biosynthesis protein Cap5O polysaccharides and lipopolysaccharides SA0139 cap5D capsular polysaccharide Biosynthesis and degradation of surface -1.53 0.00 -1.85 1.65 0.00 0.00 biosynthesis protein Cap5D polysaccharides and lipopolysaccharides SA1329 femC glutamine synthetase FemC Biosynthesis of murein sacculus and -2.14 0.00 0.00 -2.44 0.00 0.00 peptidoglycan SA0245 lytS sensor histidine kinase LytS Biosynthesis of murein sacculus and -1.70 0.00 -1.69 2.21 2.05 0.00 peptidoglycan SA1609 pbp3 penicillin-binding protein 3 Biosynthesis of murein sacculus and -1.66 0.00 0.00 -1.75 -1.90 0.00 peptidoglycan SA1195 mraY phospho-N-acetylmuramoyl- Biosynthesis of murein sacculus and -1.56 -1.80 0.00 -4.88 0.00 0.00 pentapeptide-transferase peptidoglycan SA0193 NA maltose ABC transporter, maltose- Other -2.68 -3.66 0.00 -1.81 -5.93 0.00 binding protein, putative SA2409 fmhA fmhA protein Other -2.56 0.00 0.00 -2.37 0.00 0.00 SA1806 sasC probable ATP-dependent helicase Other -2.29 -1.77 0.00 0.00 0.00 0.00 SA2582 NA membrane protein, putative Other -2.15 0.00 0.00 -4.88 -1.95 1.63 SA1045 NA iron compound ABC transporter, Other -2.11 0.00 0.00 0.00 0.00 0.00 iron compound-binding protein SA2676 sasA LPXTG cell wall surface anchor Other -1.87 0.00 1.75 -3.29 0.00 1.85 3

family protein SA1140 sasE LPXTG cell wall surface anchor Other -1.77 0.00 0.00 0.00 0.00 0.00 protein SA0411 NA membrane protein, putative Other -1.72 0.00 0.00 -2.68 0.00 0.00 SA0189 NA hypothetical protein Other -1.68 0.00 0.00 0.00 0.00 0.00 SA2167 NA iron compound ABC transporter, Other -1.63 0.00 -1.98 2.29 0.00 0.00 iron compound-binding protein SA2407 NA lipoprotein, putative Other -1.59 0.00 0.00 0.00 0.00 0.00 SA2505 sasG cell wall surface anchor family Other -1.56 0.00 -1.97 2.08 0.00 0.00 protein SA2082 NA membrane protein, putative Other -1.54 0.00 0.00 -8.74 0.00 2.80 SA2272 modA molybdenum ABC transporter, Other -1.53 0.00 -2.08 2.39 0.00 0.00 molybdenum-binding protein ModA SA2409 fmhA fmhA protein Other -2.56 0.00 0.00 -2.37 0.00 0.00

Cellular processes

SA2437 bcr bicyclomycin resistance protein Toxin production and resistance -1.86 0.00 0.00 -3.75 -1.84 0.00 SA2460 NA drug transporter, putative Toxin production and resistance -1.74 0.00 0.00 -2.97 0.00 0.00 SA2257 NA drug transporter, putative Toxin production and resistance -1.73 0.00 0.00 -3.10 0.00 0.00 SA2347 NA drug resistance transporter, Toxin production and resistance -1.57 0.00 -1.66 -1.72 0.00 1.56 EmrB/QacA subfamily SA2054 rpoF RNA polymerase sigma-37 factor Adaptations to atypical conditions -1.77 0.00 0.00 -6.13 0.00 0.00 SA1970 sspB2 cysteine protease precursor SspB Pathogenesis -1.81 0.00 0.00 -2.09 0.00 0.00 SA1328 glnR glutamine synthetase repressor Toxin production and resistance -2.74 -2.59 -2.30 -2.29 0.00 0.00 SA2025 argC2 accessory gene regulator protein C Pathogenesis -1.91 0.00 0.00 -1.90 -1.95 0.00 SA2409 fmhA fmhA protein Toxin production and resistance -2.56 -2.40 -2.60 -2.37 0.00 1.90 SA2627 betA choline dehydrogenase Adaptations to atypical conditions -2.51 -2.20 -1.80 -2.68 0.00 2.30 SA1437 NA cold shock protein, CSD family Adaptations to atypical conditions -2.17 -2.90 -2.95 -2.65 0.00 2.50 SA1753 NA universal stress protein family Adaptations to atypical conditions -1.99 0.00 -1.52 2.00 0.00 0.00 SA0861 NA cold shock protein, CSD family Adaptations to atypical conditions -1.95 0.00 0.00 -1.87 0.00 0.00 SA2731 NA cold shock protein, CSD family Adaptations to atypical conditions -1.77 0.00 0.00 -2.32 0.00 0.00 SA2054 rpoF RNA polymerase sigma-37 factor Adaptations to atypical conditions -1.77 0.00 0.00 -6.13 0.00 0.00 SA0609 sdrD sdrD protein Cell adhesion -2.71 0.00 -2.32 0.00 0.00 2.60 SA2738 trmE tRNA modification GTPase TrmE Detoxification -1.61 0.00 0.00 0.00 0.00 0.00 SA0270 NA staphyloxanthin biosynthesis Pathogenesis -7.13 -1.85 0.00 -6.30 0.00 0.00 4

protein, putative SA2291 NA staphyloxanthin biosynthesis Pathogenesis -4.15 -3.08 -2.07 -13.34 -3.74 6.54 protein SA2581 NA staphyloxanthin biosynthesis Pathogenesis -3.55 0.00 0.00 -3.17 0.00 0.00 protein SA0095 spa immunoglobulin G binding protein Pathogenesis -2.77 0.00 0.00 1.93 0.00 0.00 A precursor SA2652 clfB clumping factor B Pathogenesis -2.50 0.00 0.00 -5.94 0.00 1.67 SA2023 agrB accessory gene regulator protein B Pathogenesis -1.96 -1.87 -1.61 -2.21 0.00 0.00 SA2025 argC2 accessory gene regulator protein C Pathogenesis -1.91 -1.90 -1.78 -1.90 -1.95 0.00 SA1970 sspB2 cysteine protease precursor SspB Pathogenesis -1.81 0.00 0.00 -2.09 0.00 0.00 SA1184 NA exfoliative toxin, putative Pathogenesis -1.78 0.00 0.00 -1.61 0.00 0.00 SA2287 sarR staphylococcal accessory regulator Pathogenesis -1.64 -1.80 -1.73 0.00 0.00 0.00 R SA0096 sarS staphylococcal accessory regulator Toxin production and resistance -2.81 -1.90 -1.86 0.00 0.00 0.00 S SA1328 glnR glutamine synthetase repressor Toxin production and resistance -2.74 -2.59 0.00 -2.29 0.00 0.00 SA2409 fmhA fmhA protein Toxin production and resistance -2.56 0.00 0.00 -2.37 0.00 0.00 SA0935 dltA D-alanine-activating enzyme/D- Toxin production and resistance -2.13 0.00 -2.09 -4.78 -2.16 1.75 alanine-D-alanyl carrier protein ligase SA2437 bcr bicyclomycin resistance protein Toxin production and resistance -1.86 0.00 0.00 -3.75 -1.84 0.00 SA0746 norR transcriptional regulator, MarR Toxin production and resistance -1.80 1.91 -1.53 -6.32 -1.58 0.00 family SA1184 NA exfoliative toxin, putative Toxin production and resistance -1.78 0.00 0.00 -1.61 0.00 0.00 SA2460 NA drug transporter, putative Toxin production and resistance -1.74 0.00 0.00 -2.97 0.00 0.00 SA2257 NA drug transporter, putative Toxin production and resistance -1.73 0.00 0.00 -3.10 0.00 0.00 SA1173 hlY alpha-hemolysin precursor Toxin production and resistance -1.66 0.00 0.00 0.00 0.00 0.00 SA1152 NA colicin V production protein, Toxin production and resistance -1.57 0.00 0.00 0.00 0.00 0.00 putative SA2347 NA drug resistance transporter, Toxin production and resistance -1.57 0.00 -1.66 -1.72 0.00 1.56 EmrB/QacA subfamily SA1812 rot repressor of toxins Toxin production and resistance -1.56 -1.78 -1.54 0.00 0.00 1.70 SA1396 fmtC fmtC protein Toxin production and resistance -1.54 -2.80 -2.19 0.00 -1.94 0.00

Central intermediary metabolism 5

SA2395 narG respiratory nitrate reductase, alpha Nitrogen metabolism -1.55 0.00 0.00 0.00 11.95 0.00 subunit SA1837 metK S-adenosylmethionine synthetase One-carbon metabolism -1.55 0.00 0.00 -5.43 0.00 1.83 SA1760 ackA acetate kinase Other -2.05 0.00 -1.84 -2.10 1.97 1.56 SA2535 NA D-isomer specific 2-hydroxyacid Other -1.75 0.00 0.00 -5.12 4.59 0.00 dehydrogenase family protein SA1976 NA nitric-oxide synthase, oxygenase Other -1.61 0.00 0.00 0.00 0.00 1.52 subunit SA1760 ackA acetate kinase Other -2.05 0.00 -1.84 -2.10 1.97 1.56

DNA metabolism

SA1357 NA thermonuclease precursor family Degradation of DNA -1.61 0.00 0.00 0.00 0.00 0.00 protein SA0438 ssb2 single-stranded DNA-binding DNA replication, recombination, and repair -2.53 0.00 0.00 -1.89 0.00 2.30 protein SA1691 recJ single-stranded-DNA-specific DNA replication, recombination, and repair -2.12 0.00 0.00 0.00 0.00 0.00 exonuclease RecJ SA1614 nfo endonuclease IV DNA replication, recombination, and repair -1.95 0.00 0.00 0.00 0.00 0.00 SA0627 ung uracil-DNA glycosylase DNA replication, recombination, and repair -1.77 0.00 0.00 0.00 0.00 0.00 SA1374 lexA LexA repressor DNA replication, recombination, and repair -1.70 0.00 0.00 0.00 0.00 0.00 SA0526 NA DNA polymerase III, delta prime DNA replication, recombination, and repair -1.61 0.00 0.00 0.00 0.00 0.00 subunit, putative SA0180 NA type I restriction-modification Restriction/modification -2.35 -1.64 0.00 -2.58 -1.83 0.00 enzyme, R subunit SA0477 NA type I restriction-modification Restriction/modification -1.74 0.00 0.00 0.00 0.00 0.00 system, S subunit, EcoA family, putative SA0476 hsdM1 type I restriction-modification Restriction/modification -1.54 0.00 -1.51 0.00 -1.99 0.00 system, M subunit

Energy metabolism

SA2395 narG respiratory nitrate reductase, alpha Anaerobic -1.55 0.00 0.00 0.00 11.95 0.00 subunit SA1760 ackA acetate kinase Fermentation -2.05 -2.30 -1.84 -2.10 1.97 1.56 6

SA0008 hutH histidine ammonia-lyase Amino acids and amines -1.73 0.00 0.00 -1.67 -3.55 0.00 SA2545 sdaAB L-serine dehydratase, iron-sulfur- Amino acids and amines -1.56 -1.60 0.00 -3.08 0.00 0.00 dependent, beta subunit SA2544 sdaAA L-serine dehydratase, iron-sulfur- Amino acids and amines -1.51 -1.63 0.00 -3.15 -2.37 0.00 dependent, alpha subunit SA2301 NA formate dehydrogenase, alpha Anaerobic -1.66 0.00 -2.72 0.00 0.00 -2.14 subunit, putative SA2395 narG respiratory nitrate reductase, alpha Anaerobic -1.55 0.00 0.00 0.00 11.95 0.00 subunit SA0517 treC alpha-amylase family protein Biosynthesis and degradation of -1.53 0.00 0.00 0.00 0.00 0.00 polysaccharides SA1068 qoxC quinol oxidase, subunit III Electron transport -4.18 -2.68 -2.27 0.00 0.00 0.00 SA1067 qoxD quinol oxidase, subunit IV Electron transport -3.10 -2.50 -2.67 0.00 0.00 0.00 SA1069 qoxA quinol oxidase, subunit I Electron transport -2.31 -2.04 -3.04 0.00 0.00 0.00 SA1070 qoxB quinol oxidase, subunit II Electron transport -2.24 -1.52 -2.85 0.00 0.00 2.47 SA0190 NA NAD(P)H dehydrogenase Electron transport -1.65 0.00 0.00 2.30 0.00 0.00 (quinone), putative SA1914 NA iron-sulfur cluster-binding protein, Electron transport -1.63 0.00 0.00 -1.73 -3.01 2.68 putative SA1525 fer ferredoxin Electron transport -1.52 0.00 0.00 0.00 0.00 0.00 SA1760 ackA acetate kinase Fermentation -2.05 0.00 -1.84 -2.10 1.97 1.56 SA1734 gapA2 glyceraldehyde 3-phosphate Glycolysis/gluconeogenesis -3.27 -1.92 0.00 -2.23 -5.63 2.62 dehydrogenase SA1320 glpK glycerol kinase Other -1.64 -1.56 0.00 -5.83 -3.98 1.86 SA2329 rpiA ribose 5-phosphate isomerase Pentose phosphate pathway -1.81 0.00 0.00 0.00 0.00 0.00 SA2135 manA1 mannose-6-phosphate isomerase, Sugars -2.47 -2.40 -1.59 -6.41 -4.29 2.67 class I SA2664 manA2 mannose-6-phosphate isomerase Sugars -1.67 -2.24 -1.76 0.00 -1.79 0.00 SA2332 galM aldose 1-epimerase Sugars -1.62 0.00 0.00 2.19 0.00 0.00 SA1160 sdhB succinate dehydrogenase, iron- TCA cycle -1.81 -1.72 0.00 -2.75 -1.75 0.00 sulfur protein SA1158 sdhC succinate dehydrogenase, TCA cycle -1.65 -1.73 0.00 -2.98 -1.78 0.00 cytochrome b558 subunit SA2623 mqo2 malate:quinone oxidoreductase TCA cycle -1.51 0.00 -1.62 0.00 0.00 0.00

Fatty acid and phospholipid metabolism 7

SA1661 NA acetyl-CoA carboxylase, biotin Biosynthesis -2.07 -1.93 0.00 0.00 -3.56 0.00 carboxylase, putative SA1662 NA acetyl-CoA carboxylase, biotin Biosynthesis -1.94 0.00 0.00 0.00 0.00 0.00 carboxyl carrier protein, putative SA1747 accA acetyl-CoA carboxylase, carboxyl Biosynthesis -1.57 0.00 0.00 0.00 0.00 0.00 transferase, alpha subunit SA0317 NA lipase precursor, interruption Degradation -3.27 -2.53 0.00 0.00 0.00 0.00 SA0078 plc 1-phosphatidylinositol Degradation -1.60 0.00 0.00 0.00 0.00 0.00 phosphodiesterase

Protein fate

SA1667 NA peptidase, U32 family Degradation of proteins, peptides, and -1.93 -1.80 -1.79 -3.70 -1.77 1.77 glycopeptides SA1036 NA protease, putative Degradation of proteins, peptides, and -1.83 0.00 0.00 -1.81 0.00 0.00 glycopeptides SA1970 sspB2 cysteine protease precursor SspB Degradation of proteins, peptides, and -1.81 0.00 0.00 -2.09 0.00 0.00 glycopeptides SA1756 pepQ truncated amidase Degradation of proteins, peptides, and -1.77 0.00 0.00 -1.72 0.00 0.00 glycopeptides SA1692 NA protein-export membrane protein Protein and peptide secretion and -1.68 0.00 0.00 -4.52 -2.11 1.67 SecDF trafficking SA2675 NA SecY/Sec61-alpha family protein Protein and peptide secretion and -1.67 0.00 0.00 0.00 0.00 0.00 trafficking SA1208 lspA lipoprotein signal peptidase Protein and peptide secretion and -1.59 0.00 0.00 -1.65 0.00 0.00 trafficking SA1251 NA cell division protein FtsY, putative Protein and peptide secretion and -1.51 0.00 0.00 -1.59 0.00 0.00 trafficking SA1722 tig trigger factor Protein folding and stabilization -1.57 1.53 0.00 0.00 0.00 1.92 SA1227 def2 polypeptide deformylase Protein modification and repair -1.71 0.00 0.00 0.00 0.00 0.00 SA1970 sspB2 cysteine protease precursor SspB Degradation of proteins, peptides, and -1.81 0.00 0.00 -2.09 0.00 0.00 glycopeptides

Protein synthesis

SA1726 rpmI ribosomal protein L35 Ribosomal proteins: synthesis and -3.05 -2.80 -2.50 -3.83 0.00 0.00 8

modification SA0585 rplJ ribosomal protein L10 Ribosomal proteins: synthesis and -2.65 -1.76 -1.84 -5.62 -2.27 2.50 modification SA1725 rplT ribosomal protein L20 Ribosomal proteins: synthesis and -2.61 -2.16 0.00 -6.54 0.00 3.73 modification SA0586 rplL ribosomal protein L7/L12 Ribosomal proteins: synthesis and -2.55 -2.12 -1.71 -7.84 -1.63 1.72 modification SA1254 rpsP ribosomal protein S16 Ribosomal proteins: synthesis and -2.55 0.00 0.00 -3.79 0.00 1.65 modification SA1769 rpsD ribosomal protein S4 Ribosomal proteins: synthesis and -2.43 -1.96 0.00 -3.20 -2.02 2.76 modification SA0439 rpsR ribosomal protein S18 Ribosomal proteins: synthesis and -2.31 0.00 0.00 -4.40 0.00 0.00 modification SA2224 rplF ribosomal protein L6 Ribosomal proteins: synthesis and -2.30 0.00 0.00 -2.28 0.00 1.86 modification SA0590 NA 30S ribosomal protein L7 Ae Ribosomal proteins: synthesis and -2.18 0.00 0.00 -6.05 0.00 0.00 modification SA2233 rpsC ribosomal protein S3 Ribosomal proteins: synthesis and -2.05 -1.95 0.00 -3.71 -3.58 2.53 modification SA2740 rpmH ribosomal protein L34 Ribosomal proteins: synthesis and -2.02 0.00 0.00 -2.50 0.00 0.00 modification SA0437 rpsF ribosomal protein S6 Ribosomal proteins: synthesis and -2.02 -1.63 0.00 -5.08 -1.50 3.13 modification SA2215 rpsM ribosomal protein S13/S18 Ribosomal proteins: synthesis and -2.01 -1.55 0.00 -2.54 -1.50 1.61 modification SA1642 rpsT ribosomal protein S20 Ribosomal proteins: synthesis and -1.98 0.00 0.00 -3.44 0.00 0.00 modification SA2236 rplB ribosomal protein L2 Ribosomal proteins: synthesis and -1.95 -1.71 0.00 -4.05 0.00 2.87 modification SA1137 rpmF ribosomal protein L32 Ribosomal proteins: synthesis and -1.93 -1.66 0.00 0.00 0.00 0.00 modification SA2232 rplP ribosomal protein L16 Ribosomal proteins: synthesis and -1.93 -1.72 0.00 -2.45 0.00 0.00 modification SA2228 rplX ribosomal protein L24 Ribosomal proteins: synthesis and -1.90 0.00 0.00 -3.08 0.00 0.00 modification SA1257 rplS ribosomal protein L19 Ribosomal proteins: synthesis and -1.89 0.00 0.00 -4.21 -1.76 0.00 modification 9

SA0592 rpsG ribosomal protein S7 Ribosomal proteins: synthesis and -1.81 -1.84 -1.75 -7.36 -1.70 1.52 modification SA2223 rplR ribosomal protein L18 Ribosomal proteins: synthesis and -1.81 -1.52 0.00 -2.59 0.00 1.86 modification SA2225 rpsH ribosomal protein S8 Ribosomal proteins: synthesis and -1.80 -1.56 0.00 -2.62 0.00 1.66 modification SA1700 rpmA ribosomal protein L27 Ribosomal proteins: synthesis and -1.78 0.00 0.00 0.00 0.00 1.59 modification SA2230 rpsQ ribosomal protein S17 Ribosomal proteins: synthesis and -1.78 0.00 0.00 -2.11 0.00 0.00 modification SA1238 rpmB ribosomal protein L28 Ribosomal proteins: synthesis and -1.75 0.00 0.00 0.00 0.00 0.00 modification SA2212 rplQ ribosomal protein L17 Ribosomal proteins: synthesis and -1.75 0.00 0.00 -2.21 0.00 0.00 modification SA1292 rpsO ribosomal protein S15 Ribosomal proteins: synthesis and -1.72 0.00 0.00 0.00 0.00 0.00 modification SA2220 rplO ribosomal protein L15 Ribosomal proteins: synthesis and -1.72 -1.51 0.00 -2.09 0.00 0.00 modification SA2235 rpsS ribosomal protein S19 Ribosomal proteins: synthesis and -1.70 -2.66 0.00 -4.45 -1.65 2.41 modification SA2237 rplW ribosomal protein L23 Ribosomal proteins: synthesis and -1.70 0.00 0.00 -5.26 -1.51 3.77 modification SA2221 rpmD ribosomal protein L30p/L7e Ribosomal proteins: synthesis and -1.69 0.00 0.00 0.00 0.00 0.00 modification SA2227 rplE ribosomal protein L5 Ribosomal proteins: synthesis and -1.67 -1.54 0.00 -2.87 0.00 2.21 modification SA1608 rpmG2 ribosomal protein L33 Ribosomal proteins: synthesis and -1.64 0.00 0.00 0.00 0.00 0.00 modification SA2240 rpsJ ribosomal protein S10 Ribosomal proteins: synthesis and -1.63 -1.67 0.00 -7.91 -2.26 3.61 modification SA2226 rpsN2 ribosomal protein S14 Ribosomal proteins: synthesis and -1.61 0.00 0.00 -1.85 0.00 1.64 modification SA0584 rplA ribosomal protein L1 Ribosomal proteins: synthesis and -1.59 0.00 0.00 -7.34 -1.50 1.56 modification SA1632 rpsU ribosomal protein S21 Ribosomal proteins: synthesis and -1.57 0.00 0.00 0.00 0.00 0.00 modification SA2112 rpmE ribosomal protein L31 Ribosomal proteins: synthesis and -1.55 0.00 0.00 0.00 0.00 0.00 10

modification SA2231 rpmC ribosomal protein L29 Ribosomal proteins: synthesis and -1.52 -1.84 0.00 -2.69 0.00 1.56 modification SA2238 rplD ribosomal protein L4 Ribosomal proteins: synthesis and -1.52 -1.71 0.00 -7.59 0.00 3.56 modification SA1727 infC translation initiation factor IF-3 Translation factors -3.01 -1.81 0.00 -8.22 -1.83 3.95 SA2110 prfA peptide chain release factor 1 Translation factors -2.27 -2.21 -1.45 -6.77 -1.59 2.01 SA1587 efp translation elongation factor P Translation factors -1.92 0.00 -1.62 -1.72 0.00 0.00 SA2217 infA translation initiation factor IF-1 Translation factors -1.80 0.00 0.00 0.00 0.00 0.00 SA0593 fusA translation elongation factor G Translation factors -1.67 0.00 0.00 -2.71 0.00 0.00 SA1025 prfC peptide chain release factor 3 Translation factors -1.60 0.00 0.00 0.00 0.00 0.00 SA1148 pheS phenylalanyl-tRNA synthetase, tRNA aminoacylation -2.26 0.00 0.00 -4.17 0.00 1.64 alpha subunit SA1729 thrS threonyl-tRNA synthetase tRNA aminoacylation -1.95 0.00 -1.87 2.42 0.00 0.00 SA1149 pheT phenylalanyl-tRNA synthetase, beta tRNA aminoacylation -1.89 0.00 0.00 -1.97 0.00 0.00 subunit SA0009 serS seryl-tRNA synthetase tRNA aminoacylation -1.87 0.00 -1.53 0.00 0.00 0.00 SA1228 fmt methionyl-tRNA formyltransferase tRNA aminoacylation -1.76 -1.74 0.00 -1.80 0.00 0.00 SA1001 trpS tryptophanyl-tRNA synthetase tRNA aminoacylation -1.65 0.00 -1.75 0.00 -1.94 0.00 SA1962 gatC glutamyl-tRNA(Gln) tRNA aminoacylation -1.58 0.00 0.00 -4.28 -4.19 1.57 amidotransferase, C subunit SA1778 tyrS tyrosyl-tRNA synthetase tRNA aminoacylation -1.57 0.00 0.00 -4.76 0.00 0.00 SA1256 trmD tRNA (guanine-N1)- tRNA and rRNA base modification -3.31 0.00 -1.60 -2.90 0.00 0.00 methyltransferase SA1907 NA ribosomal large subunit tRNA and rRNA base modification -1.84 0.00 0.00 0.00 0.00 1.73 pseudouridine synthase, RluD subfamily SA1957 NA RNA methyltransferase, TrmA tRNA and rRNA base modification -1.84 0.00 0.00 -2.64 0.00 0.00 family SA1803 NA pseudouridine synthase, family 1 tRNA and rRNA base modification -1.73 0.00 0.00 0.00 0.00 0.00

Regulatory functions

SA1107 NA transcriptional regulator, Cro/CI DNA interactions -3.34 0.00 0.00 -4.86 1.50 0.00 family SA1328 glnR glutamine synthetase repressor DNA interactions -2.74 -2.59 0.00 -2.29 0.00 0.00 SA1552 malR maltose operon repressor DNA interactions -2.10 -2.61 0.00 -3.78 -1.77 0.00 11

SA2317 NA phosphosugar-binding DNA interactions -1.94 0.00 0.00 -1.86 0.00 0.00 transcriptional regulator SA0249 NA transcriptional regulator, GntR DNA interactions -1.89 0.00 0.00 -2.14 0.00 0.00 family SA1997 NA transcriptional regulator, GntR DNA interactions -1.88 0.00 0.00 -4.43 0.00 0.00 family SA2325 NA transcriptional regulator, LysR DNA interactions -1.68 0.00 0.00 0.00 0.00 0.00 family SA1904 NA transcriptional regulator, putative DNA interactions -1.62 0.00 0.00 0.00 0.00 0.00 SA2546 NA perfringolysin O regulator protein, Other -1.91 -2.46 0.00 -4.88 -2.73 2.03 putative SA2025 argC2 accessory gene regulator protein C Other -1.91 0.00 0.00 -1.90 -1.95 0.00 SA1232 NA protein kinase. POINT Protein interactions -1.95 0.00 0.00 -4.17 -1.91 1.74 MUTATION SA2107 NA phosphotyrosine protein Protein interactions -1.64 0.00 0.00 -2.13 0.00 0.00 phosphatase SA1210 pyrR pyrimidine operon regulatory RNA interactions -3.80 -1.62 0.00 -7.54 -4.90 4.84 protein SA2025 argC2 accessory gene regulator protein C Other -1.91 0.00 0.00 -1.90 -1.95 0.00 SA1328 glnR glutamine synthetase repressor DNA interactions -2.74 -2.59 0.00 -2.29 0.00 0.00

Signal transduction

SA2316 NA PTS system, IIBC components PTS -2.43 -2.64 0.00 -8.25 -3.83 0.00 SA0175 NA PTS system, IIABC components PTS -2.27 0.00 -1.93 -3.21 0.00 0.00 SA2552 NA PTS system, IIABC components PTS -2.14 0.00 0.00 -2.13 0.00 0.00 SA2376 NA PTS system, sucrose-specific IIBC PTS -1.88 -1.81 -1.78 -10.57 -2.24 -1.61 components, putative SA0516 NA PTS system, IIBC components PTS -1.55 0.00 0.00 -3.25 0.00 -1.57 SA2181 lacE PTS system, lactose-specific IIBC PTS -1.52 0.00 0.00 1.64 0.00 0.00 components SA2663 NA PTS system, fructose-specific PTS -1.51 0.00 0.00 0.00 -3.85 0.00 IIABC components SA2316 NA PTS system, IIBC components PTS -2.43 -2.64 0.00 -8.25 -3.83 0.00 SA0175 NA PTS system, IIABC components PTS -2.27 0.00 -1.93 -3.21 0.00 0.00 SA2552 NA PTS system, IIABC components PTS -2.14 0.00 0.00 -2.13 0.00 0.00 SA2376 NA PTS system, sucrose-specific IIBC PTS -1.88 -1.81 0.00 -10.57 -2.24 -1.61 12

components, putative SA0516 NA PTS system, IIBC components PTS -1.55 0.00 0.00 -3.25 0.00 -1.57 SA2181 lacE PTS system, lactose-specific IIBC PTS -1.52 0.00 0.00 1.64 0.00 0.00 components SA2663 NA PTS system, fructose-specific PTS -1.51 0.00 0.00 0.00 -3.85 0.00 IIABC components

Transcription

SA1222 rpoZ DNA-directed RNA polymerase, DNA-dependent RNA polymerase -1.93 -1.80 -1.90 0.00 0.00 0.00 omega subunit SA2213 rpoA DNA-directed RNA polymerase, DNA-dependent RNA polymerase -1.81 -1.90 -1.70 0.00 0.00 1.71 alpha subunit SA2072 NA ATP-dependent RNA helicase, Other -2.80 0.00 0.00 -5.30 0.00 2.83 DEAD/DEAH box family SA1615 NA ATP-dependent RNA helicase, Other -1.75 0.00 0.00 -2.12 0.00 0.00 DEAD/DEAH box family SA1255 rimM 16S rRNA processing protein RNA processing -2.14 0.00 0.00 -1.83 0.00 0.00 RimM SA2739 rnpA ribonuclease P protein component RNA processing -1.67 0.00 0.00 -1.99 0.00 0.00 SA2054 rpoF RNA polymerase sigma-37 factor Transcription factors -1.77 0.00 0.00 -6.13 0.00 0.00 SA2055 rsbW anti-sigma B factor Transcription factors -1.50 0.00 -1.87 -2.66 0.00 0.00

Transport and binding proteins

SA0303 NA acid phosphatase5-nucleotidase, Other -2.87 0.00 0.00 0.00 0.00 0.00 lipoprotein e(P4) family SA0689 NA ABC transporter, permease protein Unknown substrate -5.55 0.00 0.00 -5.72 -3.23 0.00 SA0690 NA ABC transporter, ATP-binding Unknown substrate -5.25 0.00 0.00 -3.63 -8.28 2.10 protein SA0688 NA ABC transporter, substrate-binding Unknown substrate -5.20 0.00 0.00 -5.09 -3.91 0.00 protein SA2401 NA formate/nitrite transporter family Anions -3.88 0.00 -1.89 -3.06 0.00 0.00 protein SA0566 nupC nucleoside permease NupC Nucleosides, purines and pyrimidines -3.84 -2.89 0.00 -4.88 0.00 1.62 SA1108 NA spermidine/putrescine ABC Amino acids, peptides and amines -3.70 0.00 0.00 -4.75 0.00 0.00 transporter, ATP-binding protein 13

SA0192 NA maltose ABC transporter, ATP- Carbohydrates, organic alcohols, and acids -3.63 -3.52 0.00 -2.01 -9.14 2.68 binding protein, putative SA0093 NA L-lactate permease Carbohydrates, organic alcohols, and acids -3.41 -2.80 -2.78 -6.89 -1.81 1.99 SA2632 cudT osmoprotectant transporter, BCCT Amino acids, peptides and amines -3.35 0.00 0.00 -5.02 0.00 0.00 family SA1084 NA cobalt transport family protein Cations and iron carrying compounds -3.13 0.00 0.00 -3.92 0.00 0.00 SA2521 NA transporter, putative Unknown substrate -3.04 -2.30 -1.50 -6.69 -4.57 0.00 SA0701 NA nucleoside permease NupC, Nucleosides, purines and pyrimidines -2.99 -1.61 -2.02 -4.65 0.00 1.62 putative SA1110 NA spermidine/putrescine ABC Amino acids, peptides and amines -2.90 0.00 0.00 -3.22 0.00 0.00 transporter, permease protein SA0303 NA acid phosphatase5-nucleotidase, Other -2.87 0.00 0.00 0.00 0.00 0.00 lipoprotein e(P4) family SA2525 NA ABC transporter, ATP-binding Unknown substrate -2.85 0.00 -1.67 0.00 0.00 0.00 protein SA0171 brnQ1 branched-chain amino acid Amino acids, peptides and amines -2.85 0.00 -1.89 -2.92 0.00 0.00 transport system II carrier protein SA0407 glpT glycerol-3-phosphate transporter Other -2.84 0.00 0.00 -4.08 -2.92 1.93 SA0264 NA ABC transporter, ATP-binding Unknown substrate -2.71 0.00 -1.69 0.00 1.95 0.00 protein SA0193 NA maltose ABC transporter, maltose- Carbohydrates, organic alcohols, and acids -2.68 -3.66 0.00 -1.81 -5.93 0.00 binding protein, putative SA1367 NA amino acid permease Amino acids, peptides and amines -2.63 0.00 -2.36 -5.27 0.00 0.00 SA2242 NA xanthine/uracil permease family Nucleosides, purines and pyrimidines -2.56 -2.20 0.00 -15.03 -2.15 3.07 protein SA2382 NA proton/sodium-glutamate symport Amino acids, peptides and amines -2.51 0.00 0.00 -7.71 -3.41 1.68 protein SA0099 sirA iron compound ABC transporter, Cations and iron carrying compounds -2.50 0.00 0.00 -1.81 0.00 0.00 iron compound-binding protein SirA SA1085 NA ABC transporter, ATP-binding Unknown substrate -2.49 0.00 0.00 -4.21 -1.72 1.96 protein SA1111 NA spermidine/putrescine ABC Amino acids, peptides and amines -2.45 0.00 0.00 -4.44 0.00 -2.62 transporter, spermidine/putrescine- binding protein SA2316 NA PTS system, IIBC components Carbohydrates, organic alcohols, and acids -2.43 -2.64 0.00 -8.25 -3.83 0.00 SA0194 NA maltose ABC transporter, permease Carbohydrates, organic alcohols, and acids -2.41 -2.72 0.00 0.00 -5.42 0.00 14

protein SA2340 gltS sodium:glutamate symporter Amino acids, peptides and amines -2.40 0.00 0.00 -1.81 0.00 0.00 SA1952 NA ferritins family protein Cations and iron carrying compounds -2.31 0.00 0.00 0.00 3.01 0.00 SA2335 NA ABC transporter, ATP-binding Unknown substrate -2.29 0.00 -1.70 -2.78 0.00 0.00 protein SA0175 NA PTS system, IIABC components Carbohydrates, organic alcohols, and acids -2.27 0.00 -1.93 -3.21 0.00 0.00 SA0459 pbuX xanthine permease Nucleosides, purines and pyrimidines -2.24 0.00 -1.96 -6.06 -1.94 3.43 SA0620 proP osmoprotectant proline transporter Amino acids, peptides and amines -2.16 0.00 0.00 -4.13 0.00 0.00 SA2552 NA PTS system, IIABC components Carbohydrates, organic alcohols, and acids -2.14 0.00 0.00 -2.13 0.00 0.00 SA1996 NA ABC transporter, ATP-binding Unknown substrate -2.13 0.00 0.00 -6.87 -2.59 0.00 protein SA1045 NA iron compound ABC transporter, Cations and iron carrying compounds -2.11 0.00 0.00 0.00 0.00 0.00 iron compound-binding protein SA1319 glpF glycerol uptake facilitator protein Other -2.05 0.00 0.00 -1.61 0.00 2.05 SA0088 NA Na/Pi cotransporter family protein Anions -1.95 0.00 -1.93 -1.55 0.00 0.00 SA1979 NA sodium-dependent transporter Unknown substrate -1.93 0.00 0.00 -3.40 -3.01 0.00 SA0311 NA sodium:solute symporter family Cations and iron carrying compounds -1.90 0.00 0.00 0.00 0.00 0.00 protein SA0722 NA phosphate transporter family Anions -1.90 0.00 0.00 -7.39 -2.00 2.35 protein SA2376 NA PTS system, sucrose-specific IIBC Carbohydrates, organic alcohols, and acids -1.88 -1.81 0.00 -10.57 -2.24 -1.61 components, putative SA2363 NA L-lactate permease Carbohydrates, organic alcohols, and acids -1.87 0.00 -1.71 -2.27 8.89 0.00 SA2437 bcr bicyclomycin resistance protein Other -1.86 0.00 0.00 -3.75 -1.84 0.00 SA1994 NA ABC transporter, ATP-binding Unknown substrate -1.85 0.00 0.00 -3.99 -3.87 0.00 protein SA2138 NA cation efflux family protein Cations and iron carrying compounds -1.83 0.00 0.00 0.00 0.00 0.00 SA0195 NA maltose ABC transporter, permease Carbohydrates, organic alcohols, and acids -1.82 -2.44 0.00 0.00 -6.82 0.00 protein SA2441 NA amino acid permease Amino acids, peptides and amines -1.80 0.00 0.00 -4.61 -6.14 1.63 SA1384 opuD1 osmoprotectant transporter, BCCT Amino acids, peptides and amines -1.80 0.00 0.00 0.00 -1.89 0.00 family SA0010 NA AzlC family protein Amino acids, peptides and amines -1.79 0.00 0.00 0.00 0.00 0.00 SA2460 NA drug transporter, putative Other -1.74 0.00 0.00 -2.97 0.00 0.00 SA2257 NA drug transporter, putative Other -1.73 0.00 0.00 -3.10 0.00 0.00 SA0098 sirB iron compound ABC transporter, Cations and iron carrying compounds -1.71 0.00 0.00 -2.35 0.00 0.00 permease protein SirB 15

SA2314 NA sodium/bile acid symporter family Other -1.70 0.00 0.00 0.00 0.00 0.00 protein SA1392 NA sodium:alanine symporter family Amino acids, peptides and amines -1.67 -1.60 -1.86 -2.57 -2.15 1.72 protein SA0788 NA proton-dependent oligopeptide Amino acids, peptides and amines -1.66 0.00 -1.88 0.00 -2.13 0.00 transporter family protein SA2167 NA iron compound ABC transporter, Cations and iron carrying compounds -1.63 0.00 -1.98 2.29 0.00 0.00 iron compound-binding protein SA1211 uraA uracil permease Nucleosides, purines and pyrimidines -1.58 0.00 0.00 0.00 0.00 2.08 SA1963 NA proline permease Amino acids, peptides and amines -1.57 0.00 0.00 2.18 0.00 0.00 SA2347 NA drug resistance transporter, Other -1.57 0.00 -1.66 -1.72 0.00 1.56 EmrB/QacA subfamily SA0097 sirC iron compound ABC transporter, Cations and iron carrying compounds -1.56 0.00 0.00 -2.66 0.00 0.00 permease protein SirC SA0516 NA PTS system, IIBC components Carbohydrates, organic alcohols, and acids -1.55 0.00 0.00 -3.25 0.00 -1.57 SA2181 lacE PTS system, lactose-specific IIBC Carbohydrates, organic alcohols, and acids -1.52 0.00 0.00 1.64 0.00 0.00 components SA2663 NA PTS system, fructose-specific Carbohydrates, organic alcohols, and acids -1.51 0.00 0.00 0.00 -3.85 0.00 IIABC components SA2348 NA drug transporter, putative Other -1.51 0.00 -1.25 0.00 0.00 0.00 SA2316 NA PTS system, IIBC components Carbohydrates, organic alcohols, and acids -2.43 -2.64 0.00 -8.25 -3.83 0.00 SA0175 NA PTS system, IIABC components Carbohydrates, organic alcohols, and acids -2.27 0.00 -1.93 -3.21 0.00 0.00 SA2552 NA PTS system, IIABC components Carbohydrates, organic alcohols, and acids -2.14 0.00 0.00 -2.13 0.00 0.00 SA2376 NA PTS system, sucrose-specific IIBC Carbohydrates, organic alcohols, and acids -1.88 -1.81 0.00 -10.57 -2.24 -1.61 components, putative SA0516 NA PTS system, IIBC components Carbohydrates, organic alcohols, and acids -1.55 0.00 0.00 -3.25 0.00 -1.57 SA2181 lacE PTS system, lactose-specific IIBC Carbohydrates, organic alcohols, and acids -1.52 0.00 0.00 1.64 0.00 0.00 components SA2663 NA PTS system, fructose-specific Carbohydrates, organic alcohols, and acids -1.51 0.00 0.00 0.00 -3.85 0.00 IIABC components SA0193 NA maltose ABC transporter, maltose- Carbohydrates, organic alcohols, and acids -2.68 -3.66 0.00 -1.81 -5.93 0.00 binding protein, putative SA1045 NA iron compound ABC transporter, Cations and iron carrying compounds -2.11 0.00 0.00 0.00 0.00 0.00 iron compound-binding protein SA2167 NA iron compound ABC transporter, Cations and iron carrying compounds -1.63 0.00 -1.98 2.29 0.00 0.00 iron compound-binding protein SA2437 bcr bicyclomycin resistance protein Other -1.86 0.00 0.00 -3.75 -1.84 0.00 16

SA2460 NA drug transporter, putative Other -1.74 0.00 0.00 -2.97 0.00 0.00 SA2257 NA drug transporter, putative Other -1.73 0.00 0.00 -3.10 0.00 0.00 SA2347 NA drug resistance transporter, Other -1.57 0.00 -1.66 -1.72 0.00 1.56 EmrB/QacA subfamily

Hypothetical proteins

SA1086 NA conserved hypothetical protein Conserved -2.87 0.00 0.00 0.00 0.00 2.22 SA1136 NA conserved hypothetical protein Conserved -2.80 0.00 0.00 -2.91 -2.56 1.93 SA1044 NA conserved hypothetical protein Conserved -2.77 0.00 -1.97 -2.43 0.00 0.00 SA1307 NA conserved hypothetical protein Conserved -2.62 0.00 -1.63 -2.03 0.00 0.00 TIGR00282 SA1017 NA conserved hypothetical protein Conserved -2.59 -1.61 -2.08 -3.46 -2.03 0.00 SA2334 NA conserved hypothetical protein Conserved -2.52 0.00 -2.14 -3.16 -1.61 0.00 SA0755 NA conserved hypothetical protein Conserved -2.48 0.00 -2.21 -3.61 0.00 0.00 SA0271 NA conserved hypothetical protein Conserved -2.38 0.00 0.00 -1.57 0.00 0.00 SA1664 NA conserved hypothetical protein Conserved -2.38 0.00 1.94 -2.03 2.47 0.00 TIGR00370 SA0643 NA conserved hypothetical protein Conserved -2.34 0.00 0.00 0.00 0.00 0.00 SA0711 NA conserved hypothetical protein Conserved -2.25 0.00 1.56 -7.91 -1.59 2.11 SA1935 NA conserved hypothetical protein Conserved -2.10 0.00 0.00 0.00 0.00 0.00 SA2373 NA conserved hypothetical protein Conserved -2.09 -1.83 0.00 -4.08 0.00 0.00 SA0067 NA conserved hypothetical protein Conserved -2.03 0.00 0.00 -2.77 0.00 0.00 SA1991 NA conserved hypothetical protein Conserved -2.00 0.00 0.00 -3.36 0.00 0.00 SA1701 NA conserved hypothetical protein Conserved -2.00 0.00 0.00 -5.10 0.00 0.00 SA1126 NA conserved hypothetical protein Conserved -1.99 0.00 0.00 -2.96 0.00 0.00 SA1993 NA conserved hypothetical protein Conserved -1.97 0.00 0.00 -5.25 0.00 0.00 SA1481 NA conserved hypothetical protein Conserved -1.97 0.00 0.00 -1.93 0.00 0.00 SA1805 NA ORFID:SA1805~repressor Conserved -1.96 0.00 0.00 0.00 0.00 0.00 homolog [Bacteriophage phiN315] SA0281 NA conserved hypothetical protein Conserved -1.95 0.00 0.00 0.00 0.00 0.00 SA1297 NA conserved hypothetical protein Conserved -1.93 0.00 0.00 -3.59 0.00 0.00 SA1947 NA conserved hypothetical protein Conserved -1.91 0.00 0.00 -1.79 0.00 0.00 SA0599 NA conserved hypothetical protein Conserved -1.88 0.00 0.00 -10.70 -1.83 0.00 SA0565 NA conserved hypothetical protein Conserved -1.88 -1.75 -1.58 -3.62 -1.89 0.00 SA0059 NA conserved hypothetical protein Conserved -1.87 0.00 0.00 -4.22 0.00 0.00 SA1426 NA conserved hypothetical protein Conserved -1.87 -1.61 0.00 0.00 0.00 0.00 17

SA1112 NA conserved hypothetical protein Conserved -1.82 0.00 0.00 -1.96 0.00 0.00 SA1359 NA conserved hypothetical protein Conserved -1.73 0.00 0.00 -2.66 0.00 0.00 SA2587 NA conserved hypothetical protein Conserved -1.72 0.00 0.00 0.00 0.00 0.00 SA0011 NA conserved hypothetical protein Conserved -1.71 0.00 0.00 0.00 0.00 0.00 SA0628 NA conserved hypothetical protein Conserved -1.67 0.00 0.00 0.00 0.00 0.00 SA1373 NA conserved hypothetical protein Conserved -1.66 -1.76 1.79 -6.20 -2.89 2.05 SA1388 NA conserved hypothetical protein Conserved -1.66 0.00 0.00 -1.91 -2.67 0.00 TIGR00023 SA1840 NA conserved hypothetical protein Conserved -1.64 0.00 0.00 -2.16 0.00 0.00 SA2134 NA conserved hypothetical protein Conserved -1.64 0.00 0.00 -2.46 0.00 0.00 SA1989 NA conserved hypothetical protein Conserved -1.64 0.00 0.00 -1.80 0.00 0.00 SA2661 NA conserved hypothetical protein Conserved -1.62 0.00 0.00 0.00 0.00 0.00 SA1990 NA conserved hypothetical protein Conserved -1.60 0.00 0.00 -1.98 0.00 0.00 SA1995 NA conserved hypothetical protein Conserved -1.59 0.00 0.00 -3.92 0.00 0.00 SA0974 NA conserved hypothetical protein Conserved -1.59 0.00 0.00 0.00 0.00 0.00 SA0198 NA conserved hypothetical protein Conserved -1.59 -2.63 0.00 0.00 -3.84 0.00 SA2601 NA conserved hypothetical protein Conserved -1.57 0.00 0.00 0.00 0.00 0.00 SA0662 NA conserved hypothetical protein Conserved -1.57 0.00 -1.50 -1.67 0.00 0.00 SA0489 NA conserved hypothetical protein Conserved -1.57 0.00 0.00 0.00 0.00 0.00 SA1968 NA conserved hypothetical protein Conserved -1.56 0.00 0.00 -1.71 0.00 0.00 SA2118 NA conserved hypothetical protein Conserved -1.54 0.00 0.00 0.00 0.00 0.00 SA0529 NA conserved hypothetical protein Conserved -1.54 0.00 0.00 -1.55 0.00 0.00 SA0527 NA conserved hypothetical protein Conserved -1.53 0.00 0.00 -3.38 0.00 0.00 SA2672 NA conserved hypothetical protein Conserved -1.53 0.00 0.00 -1.98 0.00 0.00 SA0528 NA conserved hypothetical protein Conserved -1.53 0.00 0.00 0.00 0.00 0.00 SA2300 NA conserved hypothetical protein Conserved -1.52 0.00 -1.93 1.55 0.00 0.00 SA1763 NA conserved hypothetical protein Conserved -1.51 0.00 0.00 0.00 0.00 0.00 SA2557 NA conserved domain protein Domain -4.03 0.00 0.00 -5.53 0.00 1.96 SA2037 NA conserved domain protein Domain -2.56 0.00 0.00 -4.04 0.00 0.00 SA1847 NA conserved domain protein, putative Domain -1.98 0.00 0.00 0.00 0.00 0.00

Unknown function

SA2536 NA hydrolase, haloacid dehalogenase- Enzymes of unknown specificity -3.03 -2.94 0.00 -2.60 -2.31 0.00 like family SA2297 NA monooxygenase family protein Enzymes of unknown specificity -2.46 0.00 -1.83 -2.02 0.00 1.75 SA0196 NA oxidoreductase, Gfo/Idh/MocA Enzymes of unknown specificity -2.19 -2.69 0.00 0.00 -9.04 0.00 18

family SA2245 NA acetyltransferase, GNAT family Enzymes of unknown specificity -1.76 0.00 0.00 0.00 0.00 0.00 SA0606 NA hydrolase, haloacid dehalogenase- Enzymes of unknown specificity -1.74 0.00 0.00 -2.17 0.00 0.00 like family SA2541 NA acetyltransferase, GNAT family Enzymes of unknown specificity -1.70 0.00 0.00 0.00 0.00 0.00 SA0197 NA oxidoreductase, Gfo/Idh/MocA Enzymes of unknown specificity -1.68 -2.11 0.00 1.78 -2.52 0.00 family SA0605 NA cytidine/deoxycytidylate deaminase Enzymes of unknown specificity -1.68 0.00 0.00 0.00 0.00 0.00 family protein, authentic frameshift SA2293 NA NAD/NADP octopine/nopaline Enzymes of unknown specificity -1.63 0.00 -2.25 -6.95 0.00 0.00 dehydrogenase family protein SA0507 NA LysM domain protein General -3.05 -1.59 -2.59 -4.46 0.00 4.61 SA2109 NA modification methylase, HemK General -2.33 -2.07 0.00 -5.21 -1.54 0.00 family SA1548 NA AtsA/ElaC family protein General -2.27 0.00 0.00 -3.27 0.00 0.00 SA0723 NA LysM domain protein General -2.17 0.00 -2.41 -4.09 -3.00 2.34 SA2328 NA abortive infection protein family General -2.14 0.00 -2.07 -3.44 -3.95 2.43 SA1118 typA GTP-binding protein TypA General -2.14 -1.77 0.00 -7.18 0.00 2.52 SA1186 NA antibacterial protein (phenol soluble General -2.07 0.00 0.00 2.92 0.00 0.00 modulin) SA0812 NA degV family protein General -2.06 -1.82 0.00 -1.68 -2.04 0.00 SA1187 NA antibacterial protein (phenol soluble General -2.03 0.00 0.00 5.18 0.00 0.00 modulin) SA0276 yukA diarrheal toxin General -1.99 0.00 0.00 -1.62 0.00 0.00 SA0772 NA exsB protein General -1.99 0.00 0.00 -2.13 0.00 0.00 SA0007 NA YjeF-related protein General -1.92 0.00 0.00 0.00 0.00 0.00 SA0553 tilS MesJ/Ycf62 family protein General -1.84 0.00 0.00 -4.15 0.00 0.00 SA0021 yycH yycH protein General -1.78 1.93 0.00 -1.65 0.00 0.00 SA2275 NA BioY family protein General -1.76 0.00 0.00 0.00 0.00 0.00 SA1807 NA rhodanese-like domain protein General -1.69 0.00 0.00 0.00 0.00 0.00 SA0777 NA urea amidolyase-related protein General -1.67 -1.63 0.00 0.00 0.00 0.00 SA2333 NA YnfA family protein General -1.67 0.00 -1.54 1.91 0.00 0.00 SA0790 NA integral membrane domain protein General -1.63 0.00 0.00 -2.17 0.00 0.00 SA1720 NA GTP-binding protein, putative General -1.62 0.00 0.00 0.00 0.00 0.00 SA2080 NA HD domain protein General -1.58 0.00 0.00 -2.22 0.00 0.00 19 a Fold value refers to expression increases or decreases for up- or down-regulated genes respectively. b 0.00 indicates data not available or no change. c Dap – Daptomycin; Van – Vancomycin; Oxa – Oxacillin; CCCP - carbonyl cyanide m-chlorophenylhydrazone; Nis – Nisin. d KVR – S. aureus vraSR- mutant KVR derived from S. aureus N315 (31).