TABLE 1.

Genes upregulated by daptomycin and their response status with other antibiotics

Category and locusbGeneProteinSubcategoryChange (fold) in expressiona
DapVanOxaCCCPNisKVRc
Amino acid biosynthesis
    SA1362homHomoserine dehydrogenaseAspartate family5.734.203.8015.910.00−2.51
    SA1430dapADihydrodipicolinate synthaseAspartate family3.760.000.0029.980.00−2.12
    SA1429asdAspartate-semialdehyde dehydrogenaseAspartate family3.242.801.9524.560.00−1.80
    SA1363thrCThreonine synthaseAspartate family3.063.202.8021.480.00−2.65
    SA1431dapBDihydrodipicolinate reductaseAspartate family2.661.902.1027.630.000.00
    SA1364thrBHomoserine kinaseAspartate family2.480.002.8019.620.00−2.08
    SA0600ilvEBranched-chain amino acid aminotransferasePyruvate family2.183.410.005.520.00−1.59
    SA0503NAtrans-sulfuration enzyme family proteinSerine family2.802.621.69−2.230.000.00
    SA0557cysKCysteine synthaseSerine family2.280.000.000.000.00−2.09
    SA0502NAdCysteine synthase/cystathionine beta-synthase family proteinSerine family2.000.000.000.000.000.00
Cell envelope
    SA2451NAAmino acid ABC transporter, amino acid-binding proteinOther2.652.250.006.750.000.00
    SA1522NAElastin binding protein, putativeBiosynthesis and degradation of surface polysaccharides and lipopolysaccharides2.390.000.005.240.00−2.42
    SA1066NAFmtBiosynthesis of murein sacculus and peptidoglycan4.932.365.44−3.130.000.00
    SA2116murABUDP-N-acetylglucosamine 1-carboxyvinyltransferase 2Biosynthesis of murein sacculus and peptidoglycan4.142.584.290.002.18−2.54
    SA0248lrgBLrgBBiosynthesis of murein sacculus and peptidoglycan3.560.000.006.620.000.00
    SA2352tcaATcaABiosynthesis of murein sacculus and peptidoglycan3.033.067.16−2.080.00−1.89
    SA0247lrgAHolin-like protein LrgABiosynthesis of murein sacculus and peptidoglycan2.700.000.0014.850.000.00
    SA1490pbp2Penicillin-binding protein 2Biosynthesis of murein sacculus and peptidoglycan2.211.742.970.000.00−2.59
    SA0263lytMPeptidoglycan hydrolaseBiosynthesis of murein sacculus and peptidoglycan2.200.000.000.000.000.00
    SA2451NAAmino acid ABC transporter, amino acid-binding proteinOther2.652.250.006.750.000.00
    SA2554NAMembrane protein, putativeOther2.030.00−1.620.005.40−2.65
Cellular processes
    SA2570NAGalactoside O-acetyltransferaseToxin production and resistance2.890.000.002.280.000.00
    SA2413NADrug resistance transporter, EmrB/QacA subfamilyToxin production and resistance2.690.000.001.850.00−1.60
    SA0754norAMultidrug resistance protein (NorA)Toxin production and resistance2.090.00−1.580.000.00−1.62
    SA2252NAAcrB/AcrD/AcrF family proteinToxin production and resistance2.040.000.000.000.000.00
    SA1003NANegative regulator of competence MecA, putativeDNA transformation2.960.002.195.900.00−1.34
    SA1891NARNA III-activating protein TRAPPathogenesis2.051.350.005.190.00−1.98
    SA1759NAUniversal stress protein familyAdaptations to atypical conditions2.742.301.9011.612.05−3.16
    SA0958NAGeneral stress protein 13Adaptations to atypical conditions2.141.901.801.870.000.00
    SA1010relA1GTP pyrophosphokinaseAdaptations to atypical conditions2.070.002.155.430.000.00
    SA2075ftsWCell division protein, FtsW/RodA/SpoVE familyCell division2.031.612.30−2.30−1.740.00
    SA0876NAArsenate reductase, putativeDetoxification2.040.000.000.000.000.00
    SA1003NANegative regulator of competence MecA, putativeDNA transformation2.960.002.195.900.00−1.34
    SA1645NAcomE operon protein 2DNA transformation2.050.000.006.800.000.00
    SA1440NAXpaC, putativeOther3.362.041.564.820.00−1.76
    SA2126luxSAutoinducer-2 production protein LuxSOther2.141.510.000.000.000.00
    SA0672sarAStaphylococcal accessory regulator APathogenesis3.811.602.83−1.951.65−1.86
    SA1891NARNA III-activating protein TRAPPathogenesis2.051.350.005.190.00−1.98
    SA2419hlgAGamma-hemolysin, component AToxin production and resistance10.182.902.206.630.000.00
    SA2712drp35drP35 proteinToxin production and resistance8.876.600.000.000.00−8.04
    SA2422hlgBGamma hemolysin, component BToxin production and resistance5.042.201.8013.770.000.00
    SA2421hlgCGamma hemolysin, component CToxin production and resistance3.521.801.708.970.000.00
    SA1441NATellurite resistance protein, putativeToxin production and resistance3.421.350.005.450.00−1.72
    SA2570NAGalactoside O-acetyltransferaseToxin production and resistance2.890.000.002.280.000.00
    SA0746norRTranscriptional regulator, MarR familyToxin production and resistance2.701.91−1.53−6.32−1.580.00
    SA2413NADrug resistance transporter, EmrB/QacA subfamilyToxin production and resistance2.690.000.001.850.00−1.60
    SA0754norAMultidrug resistance protein (NorA)Toxin production and resistance2.090.00−1.580.000.00−1.62
    SA2252NAAcrB/AcrD/AcrF family proteinToxin production and resistance2.040.000.000.000.000.00
Protein fate
    SA0570clpCATP-dependent Clp protease, ATP-binding subunit ClpC, authentic frameshiftDegradation of proteins, peptides, and glycopeptides3.981.621.904.480.00−2.47
    SA0979clpBATP-dependent Clp protease, ATP-binding subunit ClpBDegradation of proteins, peptides, and glycopeptides3.871.802.305.820.00−2.69
    SA2563NAATP-dependent Clp protease, putativeDegradation of proteins, peptides, and glycopeptides3.682.101.907.156.28−2.66
    SA1777NASerine protease HtrA, putativeDegradation of proteins, peptides, and glycopeptides3.063.435.390.000.00−2.60
    SA0833clpPATP-dependent Clp protease, proteolytic subunit ClpPDegradation of proteins, peptides, and glycopeptides2.972.011.501.740.00−1.59
    SA0595NAPeptidase, M20/M25/M40 familyDegradation of proteins, peptides, and glycopeptides2.370.000.001.880.000.00
    SA2463pepA2Glutamyl-aminopeptidaseDegradation of proteins, peptides, and glycopeptides2.090.000.003.790.00−2.06
    SA1005pepFOligoendopeptidase FDegradation of proteins, peptides, and glycopeptides2.061.991.800.00−3.230.00
    SA1897NAProtein export protein PrsA, putativeProtein and peptide secretion and trafficking9.594.463.880.000.00−6.29
    SA0969spsBSignal peptidase IBProtein and peptide secretion and trafficking2.561.823.94−2.760.00−1.48
    SA0418NAMttA/Hcf106 family proteinProtein and peptide secretion and trafficking2.140.000.000.000.000.00
    SA2016groELChaperonin, 60 kDaProtein folding and stabilization3.810.000.003.220.00−2.02
    SA1637dnaKDnaKProtein folding and stabilization3.681.761.543.750.00−2.39
    SA1638grpEHeat shock protein GrpEProtein folding and stabilization3.281.901.792.310.00−1.90
    SA2017groESChaperonin, 10 kDaProtein folding and stabilization2.842.202.302.120.000.00
    SA0556NAChaperonin, 33 kDaProtein folding and stabilization2.151.892.300.000.001.78
    SA1271hslUHeat shock protein HslVU, ATPase subunit HslUProtein folding and stabilization2.120.001.762.550.00−1.61
    SA2385NAHeat shock protein, Hsp20 familyProtein folding and stabilization2.040.001.701.830.000.00
    SA1459NAPeptide methionine sulfoxide reductase, degenerateProtein modification and repair3.082.364.570.000.00−2.64
    SA1034NALipoate-protein ligase A family proteinProtein modification and repair2.480.000.002.680.000.00
Regulatory functions
    SA1639hrcAHeat-inducible transcription repressor HrcADNA interactions3.581.530.002.510.00−2.32
    SA2147NATranscriptional antiterminator, BglG family/DNA-binding proteinDNA interactions2.39−2.980.000.00−2.34−1.52
    SA2517NATranscriptional regulator, MerR familyDNA interactions2.182.754.890.000.00−2.38
    SA2349NATranscriptional regulator, TetR familyDNA interactions2.140.000.000.000.000.00
    SA0837gapRGap transcriptional regulatorDNA interactions2.090.000.005.003.51−1.57
    SA2302NATranscriptional regulator, putativeOther3.573.834.702.180.00−3.39
    SA1398NATranscriptional regulator, putativeOther3.172.244.26−2.190.00−1.75
    SA1003NANegative regulator of competence MecA, putativeOther2.960.002.195.900.00−1.34
    SA1891NARNA III-activating protein TRAPProtein interactions2.051.350.005.190.00−1.98
    SA2147NATranscriptional antiterminator, BglG family/DNA-binding proteinDNA interactions2.39−2.980.000.00−2.34−1.52
    SA1003NANegative regulator of competence MecA, putativeOther2.960.002.195.900.00−1.34
    SA1891NARNA III-activating protein TRAPProtein interactions2.051.350.005.190.00−1.98
Signal transduction
    SA1457NAPTS system, IIA componentPTS2.922.885.443.370.00−3.39
    SA2148NAPTS system, mannitol-specific IIA componentPTS2.112.802.300.00−2.30−2.17
    SA0759NAPTS system, fructose-specific IIABC component, authentic frameshiftPTS2.110.000.000.0022.520.00
    SA1457NAPTS system, IIA componentPTS2.922.885.443.370.00−3.39
    SA1942vraRDNA-binding response regulator VraRTwo-component systems10.393.096.610.000.00−11.67
    SA1943vraSSensor histidine kinase VraSTwo-component systems9.576.157.000.000.00−17.33
  • a Expression increases and decreases for up- and down-regulated genes, respectively. 0.00 indicates data not available or no change. Dap, daptomycin; Van, vancomycin; Oxa, oxacillin; Nis, nisin.

  • b Boldface indicates genes reported as cell wall stress stimulon members by Utaida et al. (63) and/or Kuroda et al. (31).

  • c Daptomycin-challenged strain KVR versus daptomycin-challenged strain N315.

  • d NA, not available.