Table 7. GAS genes upregulated (+Z) and downregulated (-Z) on day 32 in comparison to day 16 of infection. M5005_gene Gene Description Function mean difference Z NFD Analysis Probe-set Probe # M5005_Spy1808 argS Arginyl-tRNA synthetase (EC 6.1.1.19) Protein synthesis -1.72298 -4.95958 0.14279 PPA1&2 SpM1_ChORF2151_s_at 8 M5005_Spy0317 hlyX putative hemolysin Virulence -2.02534 -4.71231 0.30786 PPA1&2 SpM1_ChORF0378_s_at 5 M5005_Spy0475 - PTS system, beta-glucoside-specific IIABC component (EC 2.7.1.69) Carbohydrate metabolism -1.47813 -4.48425 0.62109 PPA1&2 SpM1_ChORF0572_s_at 4 M5005_Spy0577 atpF ATP synthase B chain (EC 3.6.3.14) Carbohydrate metabolism -1.7496 -4.45203 0.68541 PPA1&2 SpM1_ChORF0756_s_at 11 M5005_Spy1637 lacB.2 Galactose-6-phosphate isomerase lacB subunit (EC 5.3.1.26) Carbohydrate metabolism -1.94768 -4.37397 0.86962 PPA1&2 SpM18_ChORF1990_s_at 15 M5005_Spy1485 accA Acetyl-coenzyme A carboxylase carboxyl transferase subunit beta (EC 6.4.1.2) Lipid metabolism -1.67854 -4.23953 1.30699 PPA1&2 SpM1_ChORF1743_s_at 4 M5005_Spy0500 - N-acetylmuramoyl-L-alanine amidase (EC 3.5.1.28) Cell wall metabolism -1.54852 -4.2346 1.32657 PPA1&2 SpM1_ChORF0601_s_at 12 M5005_Spy0608 rgpFc alpha-L-Rha alpha-1,3-L-rhamnosyltransferase (EC 2.4.1.-) Cell wall metabolism -0.77914 -4.07772 0.58709 PPA3 SpM1_ChORF0792_s_at M5005_Spy1697 - 4-amino-4-deoxychorismate lyase (EC 4.-.-.-) Unknown -1.55045 -4.04336 2.35339 PPA1&2 SpM18_ChORF2056_at 12 M5005_Spy1108 metK S-adenosylmethionine synthetase (EC 2.5.1.6) Cellular processing -1.57308 -3.94036 3.19399 PPA1&2 SpM1_ChORF1359_s_at 15 M5005_Spy0111 - Hypothetical protein Unknown -1.56285 -3.91447 3.44739 PPA1&2 SpM1_ChORF0130_at 16 M5005_Spy0212 - N-acetylmannosamine-6-phosphate 2-epimerase (EC 5.1.3.9) Carbohydrate metabolism -1.77146 -3.90173 3.5792 PPA1&2 SpM1_ChORF0251_s_at 14 M5005_Spy0782 ptsC PTS system, mannose/fructose family IIC component Carbohydrate metabolism -1.59495 -3.87937 3.82247 PPA1&2 SpM1_ChORF1059_s_at 1 M5005_Spy0839 - Hypothetical membrane spanning protein Unknown -2.16174 -3.8708 3.9199 PPA1&2 SpM18_ChORF1077_s_at 10 M5005_Spy1500 hrcA Heat-inducible transcription repressor hrcA Information processing -1.39281 -3.85739 4.07718 PPA1&2 SpM1_ChORF1763_s_at 15 M5005_Spy1075 uvrB Excinuclease ABC subunit B Information processing -1.44698 -3.85117 4.15223 PPA1&2 SpM1_ChORF1314_s_at 6 M5005_Spy0317 hlyX putative hemolysin Virulence -1.35882 -3.8256 4.47503 PPA1&2 SpM1_ChORF0378_s_at 1 M5005_Spy1723 isp Immunogenic secreted protein Virulence -1.73905 -3.80643 4.73273 PPA1&2 SpM12_ChORF249-5_s_at 2 M5005_Spy1388 nagA N-acetylglucosamine-6-phosphate deacetylase (EC 3.5.1.25) Carbohydrate metabolism -1.41297 -3.75556 5.48859 PPA1&2 SpM1_ChORF1694_s_at 11 M5005_Spy1372 proB ABC transporter permease protein Amino acid metabolism -0.57535 -3.741 1.58237 PPA3 SpM1_ChORF1673_at M5005_Spy0760 - UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase (EC 6.3.2.13) Cell wall metabolism -2.07773 -3.67455 6.9386 PPA1&2 SpM12_ChORF281-1_s_at 6 M5005_Spy0694 clpL ATP-dependent protease ATP-binding subunit clpL Stress -1.5096 -3.64816 7.48621 PPA1&2 SpM1_ChORF0888_s_at 9 M5005_Spy0111 - Hypothetical protein Unknown -1.43271 -3.64533 7.54751 PPA1&2 SpM1_ChORF0130_at 10 M5005_Spy0006 trcF Transcription-repair coupling factor Cellular processing -1.9486 -3.6416 7.6287 PPA1&2 SpM1_ChORF0008_s_at 12 M5005_Spy0762 - Hypothetical membrane associated protein Unknown -1.27144 -3.63905 7.68488 PPA1&2 SpM1_ChORF1037_s_at 2 M5005_Spy1365 - Phospho-N-acetylmuramoyl-pentapeptide-transferase (EC 2.7.8.13) Cell wall metabolism -1.43042 -3.56309 9.55004 PPA1&2 SpM1_ChORF1662_s_at 4 M5005_Spy0866 - Phosphinothricin N-acetyltransferase (EC 2.3.1.-) Unknown -1.79138 -3.5538 9.80621 PPA1&2 SpM1_ChORF1144_s_at 12 M5005_Spy0915 ffh SIGNAL RECOGNITION PARTICLE, SUBUNIT FFH/SRP54 Secretion -1.78818 -3.55266 9.83814 PPA1&2 SpM1_ChORF1200_s_at 16 M5005_Spy1129 - CAAX amino terminal protease family Information processing -1.65336 -3.52596 10.6135 PPA1&2 SpM1_ChORF1384_s_at 3 M5005_Spy0957 - Myo-inositol-1(or 4)-monophosphatase (EC 3.1.3.25) Carbohydrate metabolism -1.96256 -3.52313 10.69928 PPA1&2 SpM1_ChORF1247_s_at 5 M5005_Spy0502 - Hypothetical exported protein Unknown -1.34858 -3.50463 11.27514 PPA1&2 SpM1_ChORF0604_s_at 1 M5005_Spy0826 potA Spermidine/putrescine transport ATP-binding protein potA Membrane transport -1.45833 -3.50146 11.37667 PPA1&2 SpM1_ChORF1102_s_at 1 M5005_Spy1007 - Phage protein Phage -0.80443 -3.48346 3.30834 PPA3 SpM49_ChORF7585-33_at M5005_Spy1699 - ATPase, AAA family Unknown -1.04994 -3.46541 12.59614 PPA1&2 SpM1_ChORF1992_s_at 12 M5005_Spy0103 - Deoxyadenosine kinase (EC 2.7.1.76) / Deoxyguanosine kinase (EC 2.7.1.113) Nucleotide metabolism -1.64916 -3.42762 14.00838 PPA1&2 SpM1_ChORF0121_s_at 11 M5005_Spy1164 gpmA Phosphoglycerate mutase (EC 5.4.2.1) Carbohydrate metabolism -1.43632 -3.40918 14.75147 PPA1&2 SpM1_ChORF1429_s_at 7 M5005_Spy1133 surA, prsA Peptidyl-prolyl cis-trans isomerase (EC 5.2.1.8) Unknown -1.51792 -3.40244 15.0323 PPA1&2 SpM1_ChORF1390_s_at 1 M5005_Spy1426 - Phage protein Phage -1.29811 -3.40119 15.08484 PPA1&2 SpM12_ChORF299-4_at 14 M5005_Spy1365 - Phospho-N-acetylmuramoyl-pentapeptide-transferase (EC 2.7.8.13) Cell wall metabolism -1.64969 -3.35533 17.1434 PPA1&2 SpM1_ChORF1662_s_at 16 M5005_Spy0762 - Hypothetical membrane associated protein Unknown -1.16777 -3.32837 18.47587 PPA1&2 SpM1_ChORF1037_s_at 6 M5005_Spy0769 - Hypothetical cytosolic protein Unknown -1.90343 -3.32384 18.70902 PPA1&2 SpM1_ChORF1046_s_at 7 M5005_Spy0671 - Transposase Mobile genetic element -1.55554 -3.26954 21.73493 PPA1&2 SpM1_ChORF0864_s_at 3 M5005_Spy1108 metK S-adenosylmethionine synthetase (EC 2.5.1.6) Cellular processing -1.43151 -3.22981 24.23765 PPA1&2 SpM1_ChORF1359_s_at 9 M5005_Spy1082 - PTS system, cellobiose-specific IIB component (EC 2.7.1.69) Carbohydrate metabolism -0.54801 -3.21765 6.92509 PPA3 SpM1_ChORF1324_s_at M5005_Spy0877 - Hypothetical protein Unknown -1.4767 -3.21674 25.11969 PPA1&2 SpM1_ChORF1156_s_at 11 M5005_Spy1500 hrcA Heat-inducible transcription repressor hrcA Information processing -1.29882 -3.16996 28.53123 PPA1&2 SpM1_ChORF1763_s_at 10 M5005_Spy1753 pbp2A Multimodular transpeptidase-transglycosylase PBP 2A Cell wall metabolism -1.71042 -3.1658 28.85535 PPA1&2 SpM1_ChORF2059_s_at 12 M5005_Spy0805 srtK Nisin biosynthesis sensor protein nisK (EC 2.7.3.-) Signal transduction -1.38837 -3.1526 29.90571 PPA1&2 SpM1_ChORF1082_at 8 M5005_Spy0614 pepT Peptidase T (EC 3.4.11.14) Amino acid metabolism -1.48608 -3.13959 30.97731 PPA1&2 SpM1_ChORF0799_s_at 3 M5005_Spy0890 ddh D-lactate dehydrogenase (EC 1.1.1.28) Carbohydrate metabolism -0.68219 -3.1307 8.76916 PPA3 SpM1_ChORF1170_s_at M5005_Spy0539 - ATP-binding protein (contains P-loop) Membrane transport -1.34349 -3.12677 32.06771 PPA1&2 SpM1_ChORF0652_s_at 6 M5005_Spy1126 - Transposase Mobile genetic element -0.50305 -3.11936 9.04149 PPA3 SpM1_ChORF0195_x_at M5005_Spy1118 - Peptidoglycan N-acetylglucosamine deacetylase (EC 3.5.1.-) Cell wall metabolism -1.68072 -3.11456 33.14006 PPA1&2 SpM1_ChORF1370_s_at 10 M5005_Spy0245 nifU, yurV IscU protein Coenzyme and cofactor metabolism -1.0746 -3.10643 33.87371 PPA1&2 SpM1_ChORF0289_s_at 10 M5005_Spy0618 cmk Cytidylate kinase (EC 2.7.4.14) Nucleotide metabolism -0.49742 -3.10238 9.46398 PPA3 SpM1_ChORF0803_s_at M5005_Spy1647 rplM LSU ribosomal protein L13P Protein synthesis -0.60018 -3.07786 10.10752 PPA3 SpM5_ChORF125g-172_at M5005_Spy1117 deaD2 ATP-dependent RNA helicase Stress -1.34055 -3.07013 37.33685 PPA1&2 SpM1_ChORF1369_s_at 13 M5005_Spy0477 - Hypothetical membrane spanning protein Unknown -1.87098 -3.06993 37.35691 PPA1&2 SpM1_ChORF0575_s_at 16 M5005_Spy1504 - Hypothetical membrane spanning protein Unknown -0.59699 -3.06489 10.46442 PPA3 SpM1_ChORF1768_s_at M5005_Spy0663 mur1.1 Autolysin (EC 3.5.1.28) Cell wall metabolism -1.65847 -3.05701 38.66882 PPA1&2 SpM1_ChORF0856_s_at 13 M5005_Spy0986 glmS Glucosamine--fructose-6-phosphate aminotransferase [isomerizing] (EC 2.6.1.16) Cell wall metabolism -1.32876 -3.05323 39.06074 PPA1&2 SpM1_ChORF1280_s_at 3 M5005_Spy0633 rplU LSU ribosomal protein L21P Protein synthesis -1.6243 -3.04644 39.7751 PPA1&2 SpM1_ChORF0819_s_at 3 M5005_Spy1722 - Hypothetical protein Unknown -1.50638 -3.01978 42.69681 PPA1&2 SpM1_ChORF2023_s_at 8 Page 1 of 5 Table 7. GAS genes upregulated (+Z) and downregulated (-Z) on day 32 in comparison to day 16 of infection. M5005_gene Gene Description Function mean difference Z NFD Analysis Probe-set Probe # M5005_Spy0746 - ABC transporter ATP-binding protein Membrane transport -1.2132 -3.00848 43.99601 PPA1&2 SpM1_ChORF1019_s_at 5 M5005_Spy1134 - O-methyltransferase (EC 2.1.1.-) Unknown -0.53901 -2.95233 14.10049 PPA3 SpM1_ChORF1391_s_at M5005_Spy1542 scrA PTS system, sucrose-specific IIABC component (EC 2.7.1.69) Carbohydrate metabolism -0.54474 -2.94861 14.23877 PPA3 SpM1_ChORF1815_s_at M5005_Spy1288 - Hypothetical cytosolic protein Unknown -0.64533 -2.92063 15.3214 PPA3 SpM1_ChORF1564_s_at M5005_Spy0688 thyA Thymidylate synthase (EC 2.1.1.45) Unknown -0.58896 -2.84554 18.61936 PPA3 SpM1_ChORF0882_s_at M5005_Spy0589 - Salt-stress induced protein Unknown -0.44126 -2.81444 20.17038 PPA3 SpM1_ChORF0770_s_at M5005_Spy1420 - Phage protein Phage -0.51926 -2.76782 22.72204 PPA3 SpM1_ChORF0999_at M5005_Spy1764 ctsR Transcriptional regulator ctsR Information processing -0.45532 -2.76421 22.93151 PPA3 SpM1_ChORF2074_s_at M5005_Spy1540 endoS Endo-beta-N-acetylglucosaminidase F2 precursor (EC