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Supplemental Material for the JI website Table II. Genes regulated by Irr-Ihk. SPy# Gene Encoded protein or homologue Fold-Change Growth Transcription (27 total, 23↓ and 4↑) 0164 nusG transcription anti-termination factor -1.8 EE 0349 greA transcription elongation factor -1.6 LE 0583 stress response transcription regulator -1.5 LE 0728 septation ring formation regulator -1.7 LE 0875 two-component sensor histidine kinase -1.6 LE 1107 two-component sensor histidine kinase -1.5 & -1.7 EE & LE 1210 putative transcription regulator, gntR family -2.0 EE ATP-dependent RNA helicase -2.6 LE 1427 transcription regulator -2.4 LE 1556 two-component response regulator -1.9 EE transcription regulator -1.6 EE 1659 ATP-dependent RNA helicase -2.1 LE 1699 transcription regulator, tetR family -1.5 LE -1.9 & -1.6 EE & LE 1415 1605 1717 deaD rocA copY negative transcriptional regulator-copper transport 1777 codY transcription pleiotropic repressor -1.7 LE 1817 scrR sucrose operon repressor -1.6 EE 1 1861 transcription regulator 1863 transcription activator regulator protein, -1.6 LE -1.7 & -1.6 EE & LE -1.6 LE -1.9 & -2.0 EE & LE merR family 1895 rpoE DNA-directed RNA polymerase 1934 transcription regulator 1957 putative transcription regulator -2.6 LE 2053 transcription regulator, sigma-factor N- -1.7 EE transcription regulator -1.7 LE DNA-directed RNA polymerase alpha +2.0 EE two-component response regulator +1.7 LE putative positive regulator +1.8 LE chromosome segregation protein +1.5 EE terminal domain 2054 0080 rpoA subunit 0528 vicR 0533 2217 spoJ Virulence-associated (5 total, 4↓ and 1↑) 0738 sagA streptolysin S -2.0 EE 1013 fbp fibronectin-binding protein-like protein A -1.8 LE 1436 mf3 deoxyribonuclease (DNase) -1.8 LE 2043 mf deoxyribonuclease (DNase) -1.9 EE 67 kDa myosin-crossreactive streptococcal +1.8 EE -2.4 EE 0470 antigen Oxidative stress (5 total, 4↓ and 1↑) 0850 thioredoxin reductase 2 1374 nrdH 1681 glutaredoxin -2.1 & -2.9 EE & LE NADH peroxidase -1.8 EE 1835 trx thioredoxin -1.5 EE 0605 bsaA glutathione peroxidase +1.7 EE glucose-inhibited division protein -1.5 LE export protein for polysaccharides & teichoic -1.8 LE Cell wall synthesis (15 total, 11↓ and 4↑) 0329 gidB 0390 acids 0510 glucosyltransferase -1.6 LE 0540 putative glycosyltransferase -2.0 EE 0797 oligosaccharide translocase (flippase) -1.6 EE 1035 putative UDP-N-acetylmuramyl tripeptide -1.5 EE synthetase 1093 D-alanyl-D-alanyl-carboxypeptidase -1.7 LE 1094 putative polysaccharide deacetylase -1.9 LE 1205 UDP-N-acetylmuramoylpentapeptide-lysine -1.9 LE N(6)-alanyltransferase 1311 dltB integral membrane protein -1.8 EE 1662 mraY undecaprenyl-phosphate-UDP-MurNAc- -1.8 EE +2.1 EE +1.9 LE pentapeptide phospho-MurNAc-pentapeptide transferase 0516 0786 glucosyl transferase rgpAc rhamnosyltransferase 3 0787 rgpBc rhamnosyltransferase +1.9 LE 2185 gidA +1.7 EE methyltransferase -1.9 EE glucose-inhibited division protein Nucleotide biosynthesis (20 total, 8↓ and 12↑) 0808 0910 parC DNA topoisomerase IV, subunit C -1.6 EE 1164 topA DNA topoisomerase I -1.6 LE 1368 udk uridine kinase -1.6 EE 1375 nrdE.2 ribonucleotide reductase alpha-chain -1.7 LE DNA-directed RNA polymerase -1.6 LE 1630 2105 nrdG anaerobic ribonucleotide reductase activator -1.6 LE 2206 guaB inosine monophosphate dehydrogenase -2.0 EE DNA repair protein +1.8 EE phosphoribosylaminoimidazole - +2.1 EE 0021 0024 purC succinocarboxamide synthase 0032 purD phosphoribosylamine-glycine ligase +2.0 EE 0034 purK phosphoribosylaminoimidazole carboxylase +1.5 EE putative methyltransferase +1.7 EE II 0406 0781 dnaG DNA primase +1.7 LE 0901 pyrE putative orotate phosphoribosyltransferase +1.7 EE 1632 gmk guanylate kinase +1.7 EE 1906 hsdM type I site-specific deoxyribonuclease +1.7 LE ribonucleotide reductase +1.5 LE 1984 4 2110 nrdD anaerobic ribonucleoside-triphosphate +2.1 EE +1.6 EE reductase 2182 holB replicative DNA helicase Protein synthesis (48 total, 16↓ and 32↑) 0050 rplD 50S ribosomal protein -1.5 LE 0069 rpsE 30S ribosomal protein -1.9 EE -1.8 & -1.6 EE & LE -1.7 LE 0502 pre-protein translocase subunit 0821 putative ribosomal protein 1549 ahrC.2 arginine repressor -1.6 EE 1557 msrA -1.8 EE -1.7 & -2.0 EE & LE 1619 peptide methionine sulfoxide reductase polyribonucleotide nucleotidyltransferase 1652 nadE NAD+ synthase -2.0 LE 1672 proB gamma-glutamyl kinase -1.9 LE 1842 spi signal peptidase I -1.5 & -1.6 EE & LE glycoprotein endopeptidase -1.6 LE 50S ribosomal protein -2.3 LE 1874 1932 rplM 2072 groES heat shock protein -1.7 EE 2135 replication protein -1.8 LE -1.5 LE 2150 ahrC arginine repressor 2159 rpmF 50S ribosomal protein -1.7 & -2.3 EE & LE 0049 rplC 50S ribosomal protein +1.6 EE 0050 rplD 50S ribosomal protein +1.7 EE 0059 rpmC 50S ribosomal protein +1.9 EE 5 0060 rpsQ 30S ribosomal protein +1.5 LE 0062 rplX 50S ribosomal protein +1.8 & 1.6 EE & LE 0063 rplE 50S ribosomal protein +2.0 EE 0065 rpsH 30S ribosomal protein +1.8 EE 0066 rplF 50S ribosomal protein +1.6 EE 0067 rplR 50S ribosomal protein +1.6 & 1.6 EE & LE 0071 rpmD 50S ribosomal protein +1.9 EE 0072 rplO 50S ribosomal protein +1.9 EE 0075 infA translation initiation factor +1.9 EE 0595 lysS putative lysyl-tRNA synthetase +1.7 & 1.5 EE & LE 0611 tufA translation elongation factor +1.5 EE 0717 rpmE 50S ribosomal protein +1.5 EE 0724 rplS 50S ribosomal protein +2.2 EE 0835 carB carbamoylphosphate synthetase +1.7 LE 0740 sagC streptolysin S biosynthesis protein +2.2 LE 0870 fms peptide deformylase +1.5 EE 0902 amiC amidase +1.9 EE 1073 rplL 50S ribosomal protein +1.6 EE phosphor-2-dehydro-3-deoxyheptonatre +1.6 EE 1576 aldolase 1760 dnaK heat shock protein 70 +1.9 EE 1831 rpsF 30S ribosomal protein +1.7 EE 1991 trpG anthranilate synthase component II +1. 7 EE 6 2082 hutU 2083 urocanate hydratase +1.6 EE glutamate formiminotransferase +1.7 EE +2.1 EE 2085 fhs.2 formate-tetrahydrofolate ligase 2092 rpsB 30S ribosomal protein +1.6 & 1.5 EE & LE 2095 pepO neutral endopeptidase +1.5 LE 2183 rplI 50S ribosomal protein +2.1 EE tRNA-(5-methylaminomethyl-2- +2.1 EE 2188 thiouridylate) Transporters (45 total, 24↓ and 21↑) 0196 integral membrane protein -2.0 LE 0287 ABC transporter -1.6 LE -1.6 & -2.0 EE & LE 0323 braB branched-chain amino acid transport protein 0623 pacL calcium-transporting ATPase -1.7 LE 0631 agaV mannose-specific phosphotransferase system -2.8 EE component IIAB 0773 ABC transporter -1.9 LE 0903 ABC transporter -1.5 LE 0904 ABC transporter (permease) -1.5 LE 1018 ABC transport protein (permease) -1.6 EE 1148 ABC transporter -1.8 LE 1241 pstB phosphate ABC transporter -1.8 LE 1242 pstB2 phosphate ABC transporter -2.4 EE 1243 pstC phosphate ABC transporter (permease -1.6 LE 7 protein) 1245 pstS phosphate ABC transporter, periplasmic -1.7 LE phosphate-binding protein 1255 ABC transporter -1.9 LE 1315 putative glutamine-binding/transport -1.6 LE 1506 amino acid ABC transporter -1.6 LE 1674 ABC transporter -1.8 & -1.6 EE & LE glycerol uptake facilitator -1.5 EE 1695 sodium-dependent phosphate transporter -1.8 LE 1728 ABC transporter (permease) -1.6 LE sucrose-specific PTS permease, enzyme II -1.6 LE -1.6 EE PTS system enzyme IIB -1.9 EE short-chain fatty acids transporter +1.9 LE 0254 sugar ABC transporter +1.5 EE 0324 sodium/dicarboxylate symporter +1.6 EE ferrichrome ABC transporter +1.6 LE ABC transporter +2.2 LE PTS dependent N-acetyl-galactosamine-IIC +1.7 EE 0746 streptolysin S export protein SagI +2.3 LE 0789 ABC-transporter (permease protein) +2.3 LE uracil permease +1.7 EE PTS enzyme II component B +2.3 LE 1682 glpF 1815 scrA 1976 msmK sugar-binding ABC transport system 2051 0137 0386 atoE fhuA 0518 0630 0831 1058 agaW pyrP 8 1154 sortase +1.9 & 1.6 EE & LE 1275 amino acid ABC transporter +1.6 & 1.6 EE & LE 1276 amino acid ABC transporter +1.9 EE maltose/maltodextrin ABC transport system +1.7 LE 1784 ABC transporter +1.6 LE 1828 putative transporter +1.7 EE 1897 putative mechanosensitive ion channel +1.7 EE 1296 malG 1912 salX salivaricin A ABC transporter +1.8 EE 1917 lacE PTS system, lactose-specific component +2.4 LE +1.8 & 1.6 EE & LE +1.7 LE V-type Na+ -ATPase -1.6 EE 0176 PTS system 3-keto-L-gluconate-6-P -1.6 LE 0251 N-acetylmannosamine-6-P epimerase -1.7 LE IIBC 1918 lacF 2194 PTS system, lactose-specific component IIA ABC transporter General metabolism (61 total, 29↓ and 32↑) 0149 ntpK 0327 ntpJ V-type Na+ -ATPase subunit J -1.7 LE 0341 pgdA phosphoglycerate dehydrogenase -1.5 LE 0628 putative oligohyaluronate lyase -1. 7 EE 0720 putative phosphoesterase -1.8 LE 0722 chorismate mutase -1.7 LE 0754 atpE H+-transporting ATP synthase chain C -1.9 LE 0883 dyr dihydrofolate reductase -1.6 LE 9 1020 putative zinc-dependent hydrolase -2.3 EE tributyrin esterase -1.5 LE 1115 putative lipase/acylhydrolase -1.8 LE 1119 glutamine aminotransferase, class I -2.1 EE 1124 putative adenyate cyclase -1.6 & -1.9 EE & LE 1144 putative acetyltransferase -2.2 LE 1174 transcarboxylase subunit -1.8 LE 1177 methylmalonyl-CoA decarboxylase -2.0 EE -1.6 & -1.7 EE & LE 1022 estA 1186 citD citrate lyase acyl carrier protein 1214 lplA lipoate-protein ligase -1.6 EE 1233 coaA pantothenate kinase -2.1 EE 1250 mreA FAD synthetase -1.6 LE 1498 fps geranyltranstransferase -1.9 LE 1570 putative acetyltransferase -2.0 LE 1580 putative acetate kinase -1.6 LE 1599 beta-glucosidase -1.8 EE 1678 transaldolase -1.7 & -2.0 EE & LE 1849 pfl pyruvate formate-lyase -1.5 EE 2047 gldA glycerol dehydrogenase -1.7 LE 0023 acpP.2 acyl carrier protein +1.5 & 1.5 EE & LE 0165 nga nicotine adenine dinucleotide glycohydrolase +1.5 LE 0308 nicotinate-nucleotide adenylyltransferase +2.1 EE 0524 acetyl-CoA c-acetyltransferase +1.5 LE 10 0526 fatty acid CoA ligase +2.8 LE 0477 phosphohydrolase +1.6 LE 0720 phosphoesterase +2.1 EE fructose-1-phosphate kinase +1.5 LE 0854 fruB 1096 folC.1 folyl-polyglutamate synthetase +1.6 EE 1097 folE GTP cyclohydrolase I +1.7 EE 1126 putative ATP-NAD kinase +1.7 EE 1139 4-oxalocrotonate tautomerase +2.0 & 1.5 EE & LE 1192 citC citrate lyase synthetase +1.7 EE 1280 glmS glucosamine-fructose-6-phosphate +2.4 EE amidotransferase 1292 malM 4-alpha-glucanotransferase +1.5 LE 1544 arcB ornithine carbamoyltransferase +2.0 LE 1547 sagP arginine deaminase +1.9 LE 1744 accD acetyl-CoA carboxylase beta subunit +2.0 EE 1745 accC acetyl-CoA carboxylase +1.5 EE 1747 accB biotin carboxyl carrier protein +1.7 EE 1748 fabF beta-ketoacyl-ACP synthase II +2.1 EE 1749 fabG beta-ketoacyl-ACP reductase +1.8 EE 1750 fabD malonyl CoA-acyl carrier protein +2.0 EE transacylase 1751 fabK putative trans-2-enoyl-ACP reductase II +2.0 EE 1754 fabH beta-ketoacyl-[ACP] synthase III +1.8 EE 11 1811 scrK fructokinase +1.6 EE 1916 lacG phospho-beta-D-galactosidase +2.5 LE 1919 lacD.2 tagatose 1,6-diphosphate aldolase +2.4 LE 1922 lacB.2 galactose-6-phosphate isomerase +1.7 LE 1990 pabB +1.7 EE +1.9 & 1.7 EE & LE +1.5 LE abortive-infection phage-resistance protein -1.6 LE 0100 DNA binding -1.6 LE 0247 60 KD inner membrane protein, yidC family -1.6 & -1.8 EE & LE 0199 transposase -2.0 LE 0428 C3-family ADP-ribosyltransferase -1.9 LE 0458 putative cell division protein -1.5 LE 0504 transmembrane RNA-binding protein -1.5 LE 0552 plasmid stabilization -1.8 LE para-aminobenzoate synthetase 2184 phosphoesterase 2186 phosphohydrolase Miscellaneous (29 total, 22↓ and 7↑) 0035 abiR 0609 ftsW cell division protein -2.0 LE 0766 endA competence-associated membrane nuclease -1.8 LE 1087 srtG putative, lantibiotics-associated -1.7 EE 1201 yxlM DNA-binding protein -2.0 LE 1260 putative stress protein, gls24 family -1.5 EE 1384 putative metalloprotease -1.6 & -1.7 EE & LE -1.6 LE 1523 divIB cell division protein 12 1527 GTP-binding protein -1.7 EE 1592 putative sugar binding protein -1.6 LE 1820 stress protein -1.7 EE -1.7 EE 1823 comEB late competence protein required for DNA binding 1851 C3-degrading proteinase -1.6 LE 1884 membrane protease -1.7 EE 2045 low temperature requirement C protein -1.7 LE 0015 ftsH cell division protein +1.8 EE 0103 comYC competence protein +2.1 EE collagen-like protein +1.6 EE 1054 1191 oadA oxaloacetate decarboxylase alpha-chain +1.5 LE 1497 hlyA1 hemolysin tlyA-related protein +1.5 EE 1615 comFC late competence protein +2.2 EE +1.7 LE -1.6 & -1.5 EE & LE 2165 DNA segregation ATPase, ftsK/spoIII Phage-encoded (19 total, 15↓ and 4↑) 0555 portal protein, phage-associated 0658 cro-like protein, phage-associated -1.7 LE 0670 hypothetical, phage-associated -1.7 LE 0684 hypothetical, phage-associated -1.8 LE 0961 hypothetical, phage-associated -1.6 LE 0962 hypothetical, phage-associated -1.6 LE 1290 hypothetical, phage-associated -1.8 LE 13 1447 hypothetical, phage-associated -2.3 LE 1455 hypothetical, phage-associated -1.5 LE 1462 hypothetical, phage-associated -1.7 EE 1464 hypothetical, phage-associated -1.6 EE 1468 endonuclease, phage-associated -1.6 LE 1471 hypothetical, phage-associated -1.5 EE 1477 recombinase, phage-associated -1.8 LE 2127 hypothetical, phage-associated -2.8 LE 0957 hypothetical, phage-associated +1.6 EE 1462 hypothetical, phage-associated +1.5 LE 1465 structural protein, phage-associated +1.6 EE 1471 hypothetical, phage-associated +1.8 LE Unknown function (77 total, 62↓ and 15↑) 0105 hypothetical -1.6 & -1.6 EE & LE 0107 hypothetical -1.6 EE 0110 hypothetical -1.8 LE 0116 hypothetical -1.9 LE 0219 hypothetical -1.6 LE 0315 hypothetical -1.6 LE 0367 hypothetical -1.8 EE 0393 hypothetical -1.9 EE 0401 hypothetical -1.6 LE 0407 hypothetical -1.9 & -1.6 EE & LE 14 0430 hypothetical -1.6 & -1.6 EE & LE 0439 hypothetical -1.5 & -1.8 EE & LE 0448 hypothetical -1.6 LE 0467 hypothetical -1.9 LE 0480 hypothetical -1.9 EE 0488 hypothetical -1.6 EE 0575 hypothetical -1.6 LE 0580 hypothetical -1.7 LE 0587 hypothetical -1.7 LE 0593 hypothetical -2.0 & -2.1 EE & LE 0622 hypothetical -1.6 & -1.9 EE & LE 0653 hypothetical -1.9 & -1.7 EE & LE 0654 hypothetical -1.8 LE 0798 hypothetical -2.6 EE 0802 hypothetical -1.7 EE 0908 hypothetical-membrane spanning -1.6 LE 0912 hypothetical -1.6 LE 0914 hypothetical -1.7 & -1.8 EE & LE 0923 hypothetical -1.6 LE 1017 hypothetical -1.6 LE 1044 hypothetical-membrane spanning -1.7 & -1.5 EE & LE 1048 hypothetical -1.6 LE 1064 hypothetical -1.6 EE 15 1146 hypothetical -1.8 LE 1193 hypothetical -1.7 LE 1223 hypothetical -1. 7 EE 1253 hypothetical -1.5 & -1.6 EE & LE 1322 hypothetical -2.6 EE 1329 hypothetical -1.6 & -1.8 EE & LE 1340 hypothetical -1.9 LE 1344 hypothetical -1.7 EE 1385 hypothetical -1.7 LE 1404 hypothetical -1.6 LE 1425 hypothetical -1.8 LE 1508 hypothetical -1.6 LE 1516 hypothetical-integral membrane -2.2 LE 1534 hypothetical -1.6 LE 1569 hypothetical -1.9 LE 1571 hypothetical -1.9 & -2.3 EE & LE 1675 hypothetical -2.3 & -2.0 EE & LE 1686 hypothetical -1.8 & -2.2 EE & LE 1697 hypothetical -1.6 EE 1698 hypothetical -1.6 LE 1731 hypothetical -1.5 LE 1862 hypothetical -1.5 LE 1936 hypothetical -1.6 LE 16 1939 hypothetical -1.6 LE 1945 hypothetical -1.6 LE 2006 hypothetical -1.6 EE 2111 hypothetical -1.6 EE 2165 hypothetical -1.6 EE 2166 hypothetical -1.5 EE 0144 hypothetical +1.7 EE 0315 hypothetical +3.2 EE 0359 hypothetical +1.9 EE 0537 hypothetical +1.8 EE 0604 hypothetical +2.0 EE 1260 hypothetical +1.6 LE 1264 hypothetical +1.6 LE 1277 hypothetical +1.5 & 1.8 EE & LE 1581 hypothetical +1.6 EE 1603 hypothetical +1.6 LE 1607 hypothetical +2.0 EE 1608 hypothetical +1.7 EE 1768 hypothetical +2.0 EE 2112 hypothetical +1.6 EE 2181 hypothetical +2.3 EE Proteins encoded by differentially-expressed genes were identified by annotation or 17 homology to known proteins (http://www.ncbi.nlm.nih.gov/BLAST/) and assigned to categories based on description in Clusters of Orthologous Groups of proteins (COGs). EE, early exponential phase of growth (OD600 = 0.35); LE, late exponential phase of growth (OD600 = 0.75). 18