TABLE 1

Secreted proteins, activities, and phenotypes dependent upon T2Sa

Category and bacteriumFrequent niche/pathogenicitybSecreted protein(s)/activity(ies)Phenotype(s)Reference(s)
Human and/or animal pathogens (including some rare pathogens, as indicated)
    Acinetobacter baumanniiSoil, water/pathogen of humans (e.g., pneumonia)Lipase LipA, phospholipase LipAN, and >10 other secreted proteins identified by proteomicsSurvival in neutropenic mouse model, growth in murine pneumonia model69, 70
    Acinetobacter calcoaceticusSoil, intestinal tract/pathogen of humans (rare)Esterase, lipaseDodecane degradation71
    Acinetobacter nosocomialisSoil/pathogen of humans (rare)Lipases LipA and LipH, protease CpaA, and 57 other secreted proteins identified by proteomics72
    Aeromonas hydrophilaFreshwater or brackish water/pathogen of humans (e.g., septicemia) amphibians, and fishAerolysin (Act enterotoxin), amylase, DNase, glycerophospholipid cholesterol acyltransferase, protease, S-proteinCytotoxicity, inflammatory signaling from macrophages and epithelial cells, virulence in mice6, 7378
    Aeromonas salmonicidaFreshwater/pathogen of fish (e.g., salmon)Aerolysin79
    Burkholderia cenocepaciaSoil, water/pathogen of humans (lung infection)Lipase, polygalacturonase, proteases ZmpA and ZmpBCleavage of host tissue and defense proteins, virulence in rat lung infection, pathology in Caenorhabditis elegans infection model, virulence in onion infection, survival in macrophages, triggering IL-1β secretion from macrophages8083
    Burkholderia pseudomalleiSoil/pathogen of animals and humans (mellioidosis)Chitinase, deubiquitinase TssM, lipase, phospholipases C, proteases, and ∼40 other proteins identified by proteomicsVirulence in a hamster model, suppression of innate immune response28, 84, 85
    Burkholderia vietnamiensisSoil/pathogen of humans (lung infection)Hemolysin, phospholipase C86
    Chlamydia trachomatisHuman genital tract/pathogen of humans (STD, conjunctivitis)CPAF serine protease, putative glycogen hydrolaseIntracellular growth in epithelial cells, generation of infectious EBs, cleavage of vimentin, lamin-associated protein 1, and host antimicrobial peptides20, 8789
    Escherichia coli
        EnteroaggregativeIntestinal tract/pathogen of humans (diarrhea)Mucin-degrading metalloprotease YghJDegradation of mucous layer90
        EnterohemorrhagicIntestinal tract/pathogen of humans (diarrhea, hemolytic-uremic syndrome)Metalloprotease StcE, protein YodACleaves C1 esterase inhibitor and mucin 7, adherence to epithelia, colonization of the intestine in a rabbit model9193
        EnteropathogenicIntestinal tract/pathogen of humans (diarrhea)Outer membrane and secreted forms of lipoprotein SslEBiofilm formation, virulence in a rabbit model of disease94, 95
        EnterotoxigenicIntestinal tract/pathogen of humans (diarrhea, cholera-like)For the beta system, heat-labile (LT) toxin, mucin-degrading protease YghJ, various membrane proteinsDegradation of mucous layer, diarrhea90, 9698
For the alpha system, none identified99
        ExtraintestinalIntestinal tract/pathogen of humans (meningitis)Putative lipoprotein ECOK1_3385Protective antigen in murine sepsis model100
        UropathogenicIntestinal and urinary tracts/pathogen of humans (UTI)Surface-expressed DraD invasinAdherence to epithelial cells, survival in murine model of UTI101, 102
    Klebsiella oxytocaSoil, freshwater, plants/pathogen of humans (rare)Surface-associated pullulanase103
    Klebsiella pneumoniaeSoil, water, intestinal tract/pathogen of humans (pneumonia)PullulanaseBlockade of NF-κB in epithelial cells, growth in the murine lung104
    Legionella pneumophilaFreshwater, soil/pathogen of humans (pneumonia)Aminopeptidases LapA and LapB; chitinase ChiA; collagen-like protein Lcl; diacylglycerol lipase; endoglucanase CelA; glucoamylase GamA; glycerophospholipid cholesterol acyltransferase PlaC; lysophospholipase A PlaA; metalloprotease ProA; mono- and triacylglycerol lipase LipA; six novel proteins including NttA, NttB, and NttC; phospholipases C PlcA and PlcB; putative amidase Lpg0264; putative astacin-like peptidase LegP; putative peptidyl-proline cis-trans-isomerase; RNase SrnA; tartrate-resistant acid phosphatase; tartrate-sensitive acid phosphatase Map; triacylglycerol lipase LipB; VirK-like protein Lpg1832Virulence in murine pneumonia model (bacterial growth and tissue damage), disruption of PMN function, intracellular growth in macrophages and epithelial cells, recruitment of host GTPase Rab1B to the Legionella-containing vacuole, dampening of cytokine production by host cells, intracellular growth in environmental amoebae, colony morphology and autoaggregation, growth at low temperatures, poly-3-hydroxybutyrate storage, biofilm formation, sliding motility and surfactant production26, 4650, 5356, 5861, 105111
    Photobacterium damselaeMarine water/pathogen of fish and humans (rare)Phospholipase D Dly, pore-forming toxins HlyApl and HlyAchVirulence in marine fish112
    Pseudomonas aeruginosaSoil, plants, water/pathogen of humans (pneumonia)For the Xcp system, alkaline phosphatase PhoA; aminopeptidase PaAP; chitin-binding protein CbpD; DNase PA3909; elastases LasA and LasB; exotoxin A; glycerophosphoryl diester phosphatase GlpQ; lipases LipA and LipC; lipoxygenase LoxA; mucinases; novel proteins PA2377 and PA4140; phosphodiesterase PA3910; phospholipases C PlcH (hemolytic), PlcN, and PlcB; protease IV; putative protease PmpACytotoxicity, degradation of host tissue (e.g., in lung and eye) and surfactant proteins, disruption of cell-cell junctions (e.g., cadherin cleavage), virulence in a murine lung infection model, regulation of siderophore (pyoverdine) expression, swarming motility113122
For the Hxc system, phosphatase LapA; DING homolog LapC; surface-expressed PstSAdherence to epithelial cells, survival in low-phosphate conditions116, 123, 124
For the Txc system, chitin-binding protein CbpE125
    Pseudomonas alcaligenesSoil/pathogen of humans (rare)Lipase LipA126
    Stenotrophomonas maltophiliaSoil, water, plants/pathogen of humans (pneumonia, bacteremia)For the Xps system, proteases StmPr1 and StmPr2 and >5 secreted proteins by SDS-PAGEDetachment and cytotoxicity toward epithelial cells, degradation of extracellular matrix and cytokines127, 128
For the Gsp system, none identified yet127, 128
    Vibrio anguillarumMarine water/pathogen of fish and eelsMetalloprotease EmpA129
    Vibrio choleraeMarine water, shellfish/pathogen of humans (cholera)Aminopeptidases Lap and LapX; biofilm matrix proteins RbmA, RbmC, and Bap1; chitin-degrading enzymes including chitinase ChiA-1; chitin-binding protein GbpA; cholera toxin; collagenase VchC; cytolysin VCC; hemagglutinin-protease HapA; lipase; neuraminidase; serine proteases VesA, VesB, and VesC; TagA-related protein; and three novel proteins identified by proteomicsWatery diarrhea, degradation of mucous layers, attachment to epithelial cells, attachment to biotic (e.g., copepods) and abiotic surfaces in aquatic environments, biofilm formation, degradation of the matrix that covers the eggs of chironomids34, 35, 39, 41, 130133
    Vibrio parahaemolyticusMarine water, shellfish/pathogen of humans (gastroenteritis)Lipase134
    Vibrio vulnificusMarine water, shellfish/pathogen of humans (septicemia)Chitinase; cytolysin; elastase VvpE; hemolysin VvhA; putative peptidyl-proline cis-trans-isomerase; proteases including serine protease VvpS, sugar hydrolase, and several outer membrane proteinsCytotoxicity, virulence in murine models135137
    Yersinia enterocoliticaIntestinal tracts of mammals and various other animals/pathogen of animals and humans (gastroenteritis)For the Yts1 system, GlcNAc-binding proteins ChiY and EngY, YE3650Virulence in murine model138, 139
For the Yts2 system, none identified yetIntracellular infection of macrophages138140
Plant pathogens (including, as indicated, some that afflict humans on rare occasions)
    Burkholderia gladioliSoil, water/pathogen of various plants and fungi and humans (rare)Chitinase, proteaseCavity disease in mushrooms141
    Burkholderia glumaeSoil/pathogen of rice plantsLipase LipA, proteases, 32 other proteins identified by proteomic analysisVirulence in rice infection142, 143
    Dickeya dadantii (formerly Erwinia chrysanthemi)Soil, water/pathogen of various vegetables and flowers (soft rot)For the Out system, Avr-like protein AvrL; cellulase Cel5; esterase FaeD; pectate lyases PelA, PelB, PelC, PelD, PelE, PelI, PelL, PelN, and PelZ; pectin acetylesterase PaeY; pectin methylesterase PemA; rhamnogalacturonan lyase RhiESoft-rot disease in plants, activation of plant innate immune system, growth promotion of EHEC on lettuce144149
For the Stt system, outer membrane-anchored PnlH150
    Erwinia amylovoraSoil/pathogen of fruit (fire blight)Levansucrase, polygalacturonaseInfection of pear tissue, low-temperature growth151153
    Pectobacterium carotovorum (formerly Erwinia carotovora)Soil, water/pathogen of many plants (soft rot)Cellulases CelV and CelB; necrosis-inducing protein (Nip); pectin lyases PelA, PelB, PelC, PelZ, Pel-3, and ECA2553; novel secreted proteins ECA2134, ECA3580, and ECA3946; polygalacturonases PehA and PehX; putative cellulase ECA2220; putative proteoglycan hydrolase ECA0852; putative virulence protein SvxVirulence in plant model, maceration of tobacco leaf154157
    Pectobacterium wasabiaeSoil/pathogen of plants (wasabi)Necrosis-inducing protein (Nip)Soft-rot disease in tubers158
    Ralstonia solanacearumSoil/pathogen of many types of plants (wilt disease)Cellulase, pectin methylesterase, cellobiosidase, polygalacturonases, >30 proteins identified by proteomicsColonization of plants, causing wilting disease159, 160
    Xanthomonas axonopodisSoil, freshwater/pathogen of citrus plants (citrus canker)Cellulase, polygalacturonases, proteasesVirulence in orange leaves161, 162
    Xanthomonas campestris pv. campestrisSoil, freshwater/pathogen of crucifer plants (black rot)α-Amylase; cellulase; pectate lyase; polygalacturonases PghAxc and PghBxc; serine protease PrtA; other proteasesVirulence in Arabidopsis plant models163165
    Xanthomonas campestris pv. vesicatoriaSoil, freshwater/pathogen of pepper and tomato plants (leaf spot)For the Xps system, lipase XCV0536, protease XCV3671, and xylanases XynC, XCV4358, and XCV4360Virulence in pepper plant model166, 167
For the Xcs system, none identified yet166
    Xanthomonas oryzae pv. oryzaeSoil, freshwater/pathogen of various rice plants (rice blight)Cellulase ClsA, cysteine protease CysP2, endoglucanase EglXoB, lipase LipA, polysaccharide, putative cellobiosidase CbsA, xylanase XynBVirulence in rice infection model168173
    Xanthomonas oryzae pv. oryzicolaSoil, freshwater/pathogen of various rice plants (rice blight)Cysteine protease XOC1601, polygalacturonase XOC2128, protease EcpA, protease XOC3806Virulence in rice infection model174, 175
    Xylella fastidiosaPlant xylem/pathogen of various plants (e.g., grapes)Lipase/esterase LesAVirulence in grapevine infection176
Nonpathogens or, as indicated, bacteria that very rarely cause human disease
    Aeromonas veroniiFreshwater, leech symbiont/pathogen of humans (very rare)HemolysinColonization of the medicinal leech (symbiosis)177
    Caulobacter crescentusFreshwater/nonpathogenOuter membrane and secreted lipoprotein ElpSActivates alkaline phosphatase activity178
    Cellvibrio japonicusSoil/nonpathogenEndoglucanase179
    Cupriavidus metalliduransSoil/nonpathogenAlkaline phosphatase180
    Nonpathogenic Escherichia coliIntestinal tract/nonpathogenChitinase, lipoprotein SslE181, 182
    Geobacter sulfurreducensSediments/nonpathogenMulti-copper oxidase OmpB183
    Gluconacetobacter diazotrophicusSymbiont of sugar cane and other plants/nonpathogenLevansucrase184
    Marinobacter hydrocarbonoclasticusMarine water/nonpathogenLipaseBiofilm formation185
    Methylococcus capsulatusFresh and marine water, sediment/nonpathogenSerine protease MCA0875, surface-associated protein MCA2589, c-type cytochrome MCA0338186
    Pseudoalteromonas haloplanktisMarine water/nonpathogenProtease187
    Pseudoalteromonas ruthenicaMarine water/nonpathogenCPI protease188
    Pseudoalteromonas tunicataMarine water/nonpathogen>30 proteins identified by proteomicsIron acquisition, pigmentation189
    Pseudomonas fluorescensSoil, plants, water/nonpathogenDING homolog Psp190
    Pseudomonas putidaSoil/nonpathogenFor the Xcp system, surface-expressed phosphatase UxpBGrowth in low-phosphate media191
For the Xcm system, surface-expressed Mn-oxidizing enzyme(s)192
    Ralstonia pickettiiSoil, freshwater/primarily nonpathogen; pathogen of humans (very rare)Poly(3-hydroxybutyrate) depolymerase193
    Shewanella oneidensisWater/primarily nonpathogen; pathogen of humans (very rare)Outer membrane proteins, including c-type cytochromes MtrC and OmcA, and DMSO reductase DmsAFe(III) and Mn(IV) reduction, extracellular respiration194197
    Vibrio fischeri (now Allivibrio fischeri)Marine water, symbiont of squid/nonpathogenNAD+-glycohydrolases HvnA and HvnB18, 198
  • a Dependence is based upon the absence or reduction of the indicated protein, activity, or phenotype in a mutant(s) specifically lacking a T2S gene(s). Abbreviations: IL-1β, interleukin 1β; STD, sexually transmitted disease; CPAF, chlamydial protease-like activity factor; EBs, elementary bodies; UTI, urinary tract infection; PMN, polymorphonuclear leukocytes; EHEC, enterohemorrhagic E. coli; CPI, cysteine protease inhibitor; DMSO, dimethyl sulfoxide.

  • b Only the most common disease manifestation(s) is noted.