TABLE 1

Genes regularly present in pathogenic S. pneumoniae in contrast to related commensal species

Locus no.aAnnotation and comment(s)bPresence (%) in:
S. pneumoniaeS. pseudopneumoniaeS. mitisS. oralis
SP_0041Bacteriocin BlpO (BlpU); downregulated in CSF (14)10010000
SP_0082Pneumococcal adhesion and virulence protein B, Pav;
significantly upregulated in the heart (86)
9210050
SP_0088-9Hypothetical protein; upregulated in CSF (14)85000
SP_0102Glycosyl transferase920150
SP_0109Putative bacteriocin10001512
SP_0116Hypothetical protein1006700
SP_0117Pneumococcal surface protein A (PspA); interferes with complement activation and binds lactoferrin; significantly upregulated in blood, CSF, the heart, and epithelial contact (14, 86)100000
SP_0124-5Class IIb bacteriocins, CibA and CibB100100100
SP_0133-9Glycosyl transferase, glycosyl transferase, family 2, ABC transporter, ATP-binding protein, GlcNAc-PI de-N-acetylase, 3× hypothetical proteins100000
SP_0175-8Riboflavin biosynthesis (RibD, RibE, RibA, RibC/H); essential for intracellular survival of Brucella abortis (96)10010056
SP_0181Conserved hypothetical protein1000035
SP_0245-53Putative pyruvate formate-lyase-activating enzyme, transcriptional regulator DeoR family, transcriptional regulator, PTS, putative formate acetyltransferase, transaldolase family protein, glycerol dehydrogenase (GldA)1000200
SP_0314-5, SP_0317-30Hyaluronate lyase (Hyl) (P, H), hypothetical protein, 4-hydroxy-2-oxoglutarate aldolase, carbohydrate kinase (PfkB family), conserved domain protein, oxidoreductase (H), hyaluronate PTS transporter (L), glucuronyl hydrolase (L), preprotein translocase (YajC subunit), oligohyaluronate lyase/heparinase II/III-like protein, hypothetical protein, sugar binding transcriptional regulator (RegR) (repression of glycuronidase expression), two transposases; colonization, meningitis1000018
SP_0379MFS (major facilitator superfamily) permease (L); import or export of target substrates8510050
SP_0389Hypothetical protein/cell wall-binding repeat protein92050
SP_0390Choline-binding protein G (CbpG); upregulated in blood (14)1003306
SP_0394-7Mannitol PTS, transcriptional regulator8510000
SP_0448Hypothetical protein100000
SP_0449Hypothetical protein100100150
SP_0455Hypothetical protein92000
SP_0471-2Conserved hypothetical proteins100050
SP_0473-8Putative regulator, PTS, lactose specific, GH20_hexosaminidase superfamily domain protein, 6-phospho-β-galactosidase85050
SP_0504-10Type I restriction-modification system, M/R subunits (HsdM, HsdR); regulates capsular polysaccharide expression (32); SP_504 is missing in SPPN10010000
SP_0528Peptide pheromone BlpC1001002012
SP_0529Bacteriocin secretion accessory protein BlpC, ABC transporter851002012
SP_0576Transcription antiterminator LicT9210050
SP_0577-8Beta-glucoside PTS transporter (BglP), 6-phospho-beta-glucosidase (BglA-2)9210000
SP_0582Endonuclease; significantly downregulated in CSF (14)9210000
SP_0595-6Hypothetical protein92000
SP_0633Hypothetical protein856700
SP_0684-5Bacteriocin, lactococcin 972 family protein921001012
SP_0703-7Peptide ABC transporter; downregulated in blood (14)1000156
SP_0772Hypothetical protein100000
SP_0858-60Two membrane proteins, pyrrolidone-carboxylate peptidase (Pcp-1)10010000
SP_0886-92Type I restriction-modification system100100054
SP_0899Conserved hypothetical protein921001047
SP_0950Acetyltransferase, GNAT family85000
SP_0994Hypothetical protein10010000
SP_0997-8Hypothetical protein (SP_0997-8 constitute one ORF)10010000
SP_1032-5Iron compound ABC transporter (Pit)100000
SP_1038-40Phage-associated proteins, including site-specific resolvase100006
SP_1047-8Hypothetical protein (part of RD6); in S. mitis B6 and SK637, the two constitute a single ORF920100
SP_1108Hypothetical protein (fragment of SK142_0963)92000
SP_1210Putative bacteriocin immunity protein8510000
SP_1223-4Toxin-antitoxin module100100200
SP_1237Acetyltransferase, GNAT family1001001018
SP_1250McrBC 5-methylcytosine restriction system component100331512
SP_1251Putative endonuclease/restriction enzyme B9201024
SP_1264Conserved domain protein8510000
SP_1427Peptidase, U32 family (fragment of SK142_1155)100000
SP_1430-1Type II DNA restriction-modification system9210000
SP_1433-8Transcriptional regulator, AraC family, drug ABC transporter85000
SP_1493-5Hypothetical proteins; SP_1494 is fragment (84 aa) of 1,256- to 2,522-aa collagen binding protein (LPXTG cell wall anchor domain protein) of S. mitis1000150
SP_1500Glutamine ABC transporter (GatB), amino acid-binding protein; adhesin upregulated in contact with lung epithelia (13); remaining part of transporter (SP_1501-2) is present in all strains1001001024
SP_1550Glutathione S-transferase family protein; upregulated in CSF (14)1000200
SP_1656Hypothetical protein92000
SP_1658Membrane protein920150
SP_1679Hypothetical protein100100100
SP_1684PTS, IIBC components9210050
SP_1694Acetyl xylan esterase10010000
SP_1704-6ABC transporter, unknown function100100150
SP_1795Beta-fructosidase; pneumonia10010050
SP_1809-10Transcriptional regulator, hypothetical protein; tryptophan biosynthesis8510050
SP_1821Sugar-binding transcriptional regulator, LacI family1001002012
SP_1822Hypothetical protein8567100
SP_1823MgtC/SapB family protein/magnesium transporter1001001512
SP_1824-34Phosphate ABC transporter, hypothetical protein, UDP-glucose 4-epimerase (GalE-2), galactose-1-phosphate uridylyltransferase (GalT-1), PhoU family transcriptional regulator, two hypothetical proteins, cell wall-anchored protein, cell wall surface anchor family protein (SP_1828-30 constitute RD11)100100200
SP_1856Transcriptional regulator, MerR family, galactose operon1001001524
SP_1859Nicotinamide mononucleotide transporter PnuC1001002071
SP_1883-5Putative dextran glucosidase DexS/alpha-phosphotrehalase/alpha-amylase, trehalose PTS system, IIABC components, trehalose operon transcriptional repressor (TreR)1001001035
SP_1894Sucrose phosphorylase (GtfA)10001076
SP_1895-7Raffinose ABC transporter (RafG, RafF, RafE); upregulated in contact with lung epithelia (13)100000
SP_1898-9Alpha-galactosidase (Aga), msm operon regulatory protein (MsmR)10001076
SP_1917Hypothetical protein1000012
SP_1918ABC transporter, ATP-binding protein (fragment of SK142_1598)100000
SP_1923-6Pneumolysin (Ply), significantly upregulated in the heart (86); downregulated in CSF and by epithelial contact (14); hypothetical proteins100100150
SP_1930-3Hypothetical proteins100050
SP_1934-6Hypothetical protein, Zn-dependent peptidase ImmA, M78 family (posttranslational modification, protein turnover), type II restriction-modification system regulatory protein1006750
SP_1937Autolysin (LytA) significantly upregulated in the heart (86); downregulated in CSF (14)100100200
SP_1946Putative transcriptional regulator PlcR920100
SP_1958Hypothetical protein100050
SP_1989Transcriptional regulator PlcR920100
SP_1992Cell wall surface anchor family protein (“Xisco”)100000
SP_2016-24Nicotinate-nucleotide pyrophosphorylase (NadC); downregulated in CSF (14); dicarboxylate carrier protein; downregulated in CSF (14), ABC transporter, ATP-binding protein (truncation), transcriptional regulator, GntR family, 6-phospho-beta-glucosidase; upregulated in CSF and by epithelial contact (14), PTS; upregulated in contact with lung epithelium (13), putative lactose/cellobiose transporter (SP_2018 is degenerate transposase)100000
SP_2081-3Conserved hypothetical protein, two-component histidine transcriptional regulator PnpR/S (TCS04); activates the expression of the genes encoding the PstI transporter and PhoU1 regulator (SP_2084-8); genetic fitness, immune evasion, controls the expression of pneumococcal surface antigen (PsaA, SP_0117) (27)10010000
SP_2084-8Phosphate ABC transporter (Pst1: PstS, -C, -A, and -B proteins), phosphate system regulatory protein PhoU10010000
SP_2136Choline-binding protein PcpA; significantly upregulated in the heart (86)1003356
SP_2148-51Arginine deiminase pathway enzymes ArcA, ArgF, ArcC; orthologs in S. oralis subsp. dentisani1000029
SP_2152-3Conserved hypothetical protein, peptidase, M2i0/M25/M40 family100000
SP_2158-68Fucose utilization operon including PTS (FucI, FucU, FucA); sepsis (64); upregulated in lungs versus nasopharynx (60); SP_2162 (ptnC); SP_2164 (PM0834) (mannose family PTS (SP_1858-66 constitute RD13)850100
SP_2190/1Choline-binding protein A (PspC/CbpA)/isoprenylcysteine carboxyl methyltransferase; upregulated by epithelial contact (14); binds polymeric immunoglobulin receptor; binding of factor H minimizes the activity of the alternative pathway of complement and therefore enhances the capacity of the isolate to evade opsonophagocytosis100000
SP_2192-3Two-component histidine transcriptional regulator (TCS06); regulates CbpA (SP_2190) expression (27); present in strains of S. oralis subsp. tigurinus in the context of isoprenylcysteine carboxyl methyltransferase (ICMT) family protein and IgA-binding beta-antigen genes1000029
  • a Locus numbers in boldface refer to genes identified as associated with attenuated virulence in mouse models of pneumonia and/or bacteremia in one or more of three STM studies (1012).

  • b CSF, cerebrospinal fluid; ORF, open reading frame.