Table 1 Mutations with moderate and high effect acquired during the infections and passages.

StrainMutation*bpTypeGeneEncoded productGroupLineage
NCTC8325SNP27,460MissensewalKSensor protein kinase WalKGR | TM | ST
NCTC8325SNP98,945MissenseSAOUHSC_00092Conserved hypothetical proteinHP | TM | SEc222
NCTC8325SNP120,749Missensecap5BCapsular polysaccharide synthesis enzyme Cap5BSE | HP
NCTC8325SNP24,5287MissensetarIConserved hypothetical proteinSE | HP
NCTC8325SNP280,449MissenseessBESAT-6 secretion machinery protein EssBTM | SE | P
NCTC8325SNP393,634MissenseSAOUHSC_00390Conserved hypothetical proteinHP | P
NCTC8325SNP420,058MissenseSAOUHSC_00417Conserved hypothetical proteinTM
NCTC8325SNP464,931MissensernmVRibonuclease M5TM
NCTC8325SNP541,242MissenseSAOUHSC_00535Epimerase/dehydrataseTM
NCTC8325SNP546,984Missenseazo1FMN-dependent NADPH-azoreductaseTM
NCTC8325SNP568,990MissenseSAOUHSC_00560Conserved hypothetical proteinc222
NCTC8325SNP588,150MissenseSAOUHSC_00586Conserved hypothetical proteinSE
NCTC8325SNP706,223MissenseSAOUHSC_00723Conserved hypothetical proteinTMc222
NCTC8325SNP721,884MissenseSAOUHSC_00736Putative lipid kinaseTMc222
NCTC8325SNP778,092MissenseSAOUHSC_00795Glyceraldehyde-3-phosphate dehydrogenaseTM | HPc222
NCTC8325SNP813,228MissensemetN2Methionine import ATP-binding
protein MetN2
TM
NCTC8325SNP1,030,094MissenseSAOUHSC_01064Pyruvate carboxylaseTM
NCTC8325SNP1,067,459MissensesdhBIron-sulfur subunit of succinate dehydrogenase%2C putativeTM
NCTC8325SNP1,121,026MissensecarBCarbamoyl phosphate synthase large subunitTM
NCTC8325SNP1,138,999MissenseSAOUHSC_01187Conserved hypothetical proteinSE
NCTC8325SNP1,550,169Stop-gainSAOUHSC_01628Conserved hypothetical proteinSE
NCTC8325SNP1,727,352MissenseSAOUHSC_01821Conserved hypothetical proteinTMc222
NCTC8325SNP1,757,024MissenseccpACatabolite control protein AGR | Pc222
NCTC8325SNP1,773,253MissenseSAOUHSC_01866Conserved hypothetical proteinTM
NCTC8325SNP2,033,426MissensescniStaphylococcal complement inhibitorHP | P | SE
NCTC8325SNP2,045,511MissenseyqbOTail length tape measure proteinc222
NCTC8325SNP2,095,322MissenseagrCAccessory gene regulator protein CGR | ST | P | SE
NCTC8325SNP2,249,603MissenseSAOUHSC_02420Conserved hypothetical proteinSEc222
NCTC8325SNP2,286,918MissensehysAHyaluronate lyaseTM | CWA | Pc222
NCTC8325SNP2,311,214MissenserpsHRibosomal protein S8TMc222
NCTC8325SNP2,624,646MissenseSAOUHSC_02849Putative pyruvate oxidaseTM
NCTC8325SNP2,756,289Missenseasp2Accessory Sec system protein Asp2TM | SE
NCTC8325Ins487,126FrameshiftSAOUHSC_00488Cysteine synthaseTM
NCTC8325Del513,207FrameshiftcysESerine acetyltransferaseTM
NCTC8325Del624,930DisruptiveSAOUHSC_00634ABC transporterTM | SE
NCTC8325Ins658,822DisruptiveSAOUHSC_00670Conserved hypothetical proteinTM | SEc222
NCTC8325Del764,412DisruptivelgtProlipoprotein diacylglyceryl transferaseTM | SE
NCTC8325Del1,323,611FrameshiftoppC2Oligopeptide transporter putative
membrane permease domain
TM | SE
NCTC8325Del2,096,058FrameshiftagrAAccessory gene regulator protein AGR | ST | P
NCTC8325Ins2,188,845FrameshiftSAOUHSC_02366Conserved hypothetical proteinTM
N315SNP105,983MissenseSA_RS00630LipoproteinSE
N315SNP274,258Stop-gainSA_RS01330Acetyl-CoA/acetoacetyl-CoA transferaseTMn222
N315SNP377,083MissenseSA_RS01835PTS lactose transporter subunit IIBTM
N315SNP403,331MissensemetE5-Methyltetrahydropteroy-ltriglutamate—
homocysteine methyltransferase
TM
N315SNP572,540MissensecysSCysteine—tRNA ligaseTM
N315SNP580,166MissenserpoBDNA-directed RNA polymerase subunit betaTM
N315SNP758,669MissenseSA_RS03785Hypothetical proteinSE
N315SNP863,049MissenseosmCOrganic hydroperoxide resistance proteinHP
N315SNP949,546MissenseLysR TRLysR family transcriptional regulatorGR
N315SNP1,343,567MissensesbcCNuclease SbcCD subunit CTM
N315SNP1,471,383MissensenorBQuinolone resistance protein NorBTM | P | SE
N315SNP1,486,091MissenserecUHolliday junction resolvase RecUTM
N315SNP1,735,479MissensepykAPyruvate kinaseTMn222
N315SNP1,817,943MissenseleuSLeucine—tRNA ligaseTM
N315SNP1,948,268MissensevraSTwo-component sensor histidine kinaseGR | ST | SE | P
N315SNP2,035,898Stop-gainSA_RS10285Hypothetical proteinn222
N315SNP2,193,397MissenseSA_RS11160EVE domain–containing proteinTM
N315SNP2,320,771MissenseacrAcrB/AcrD/AcrF family proteinTM | SE
N315SNP2,393,851MissenseSA_RS12225MOSC domain–containing proteinTM
N315SNP2,575,229MissenseSA_RS13145Hypothetical proteinCWA | HP
N315SNP2,626,125MissenseSA_RS13405Membrane proteinSE
N315SNP2,637,600MissenseSA_RS13450N-succinyldiaminopimelate aminotransferaseTMn222
N315SNP2,743,605Stop-gainSA_RS13980Hypothetical proteinCWA | SE
N315SNP2,751,067Missenseasp2Accessory Sec system protein Asp2TM | SEn222
N315Del90,901FrameshiftSA_RS00555Anion membrane transporterTM | SE
N315Del1,085,977FrameshiftSA_RS05425Hypothetical proteinSE
N315Del1,473,471FrameshifttdcBl-Threonine dehydratase catabolic TdcBTM
N315Ins1,475,240Frameshiftald1Alanine dehydrogenaseTM | CWA | SE
N315Del1,947,711FrameshiftvraSTwo-component sensor histidine kinaseGR | ST | P | SE
N315Del2,568,566DisruptivefnbAFibronectin-binding protein ACWA | HP | SE | P

*Only mutations with moderate effect (missense SNPs and disruptive indels) and high effect (stop-gained and frameshifts) are listed because they are more likely to play a role in host adaptation. Mutations include SNPs, deletions (Del), and insertions (Ins). Group: HP (host-pathogen interaction), GR (gene regulation), ST (signal transduction), TM (transport and metabolism), P (pathogenesis), CWA (cell wall associated), and SE (surface associated/exported). Lineage indicates the fittest clone in which mutations were identified.