1887

Abstract

Intracellular cations are essential for the physiology of all living organisms including bacteria. Cations such as potassium ion (K), sodium ion (Na) and proton (H) are involved in nearly all aspects of bacterial growth and survival. K is the most abundant cation and its homeostasis in and is regulated by three major K transporters: high affinity transporter Kdp and low affinity transporters Kup and Trk. Previous studies have demonstrated the roles of cations and cation transport in the physiology of ; their roles in the virulence and physiology of pathogenic bacteria are not well characterized. We have previously reported that the K transporter Trk is important for the secretion of effector proteins of the type III secretion system (TTSS) of pathogenicity island 1 (SPI-1). Here we further explore the role of cation transport in virulence and pathogenesis in animal models. Impairment of K transport through deletion of K transporters or exposure to the chemical modulators of cation transport, gramicidin and valinomycin, results in a severe defect in the TTSS of SPI-1, and this defect in the TTSS was not due to a failure to regulate intrabacterial pH or ATP. Our results also show that K transporters are critical to the pathogenesis of in mice and chicks and are involved in multiple growth and virulence characteristics , including protein secretion, motility and invasion of epithelial cells. These results suggest that cation transport of the pathogenic bacterium , especially K transport, contributes to its virulence in addition to previously characterized roles in maintaining homeostasis of bacteria.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.068700-0
2013-08-01
2020-01-22
Loading full text...

Full text loading...

/deliver/fulltext/micro/159/8/1705.html?itemId=/content/journal/micro/10.1099/mic.0.068700-0&mimeType=html&fmt=ahah

References

  1. Aguirre A., Cabeza M. L., Spinelli S. V., McClelland M., García Véscovi E., Soncini F. C.. ( 2006;). PhoP-induced genes within Salmonella pathogenicity island 1. J Bacteriol188:6889–6898 [CrossRef][PubMed]
    [Google Scholar]
  2. Aizawa S. I.. ( 1996;). Flagellar assembly in Salmonella typhimurium . Mol Microbiol19:1–5 [CrossRef][PubMed]
    [Google Scholar]
  3. Akbar S., Schechter L. M., Lostroh C. P., Lee C. A.. ( 2003;). AraC/XylS family members, HilD and HilC, directly activate virulence gene expression independently of HilA in Salmonella typhimurium . Mol Microbiol47:715–728 [CrossRef][PubMed]
    [Google Scholar]
  4. Altier C., Suyemoto M., Lawhon S. D.. ( 2000;). Regulation of Salmonella enterica serovar typhimurium invasion genes by CsrA. Infect Immun68:6790–6797 [CrossRef][PubMed]
    [Google Scholar]
  5. Arricau N., Hermant D., Waxin H., Ecobichon C., Duffey P. S., Popoff M. Y.. ( 1998;). The RcsB-RcsC regulatory system of Salmonella typhi differentially modulates the expression of invasion proteins, flagellin and Vi antigen in response to osmolarity. Mol Microbiol29:835–850 [CrossRef][PubMed]
    [Google Scholar]
  6. Ausubel F. M., Brent R., Kingston R. E., Moore D. D., Seidman J. G., Smith J. A., Struhl K.. ( 1997;). Current Protocols in Molecular Biology New York: Wiley;
    [Google Scholar]
  7. Bagnara A. S., Finch L. R.. ( 1972;). Quantitative extraction and estimation of intracellular nucleoside triphosphates of Escherichia coli . Anal Biochem45:24–34 [CrossRef][PubMed]
    [Google Scholar]
  8. Bajaj V., Hwang C., Lee C. A.. ( 1995;). hilA is a novel ompR/toxR family member that activates the expression of Salmonella typhimurium invasion genes. Mol Microbiol18:715–727 [CrossRef][PubMed]
    [Google Scholar]
  9. Bajaj V., Lucas R. L., Hwang C., Lee C. A.. ( 1996;). Co-ordinate regulation of Salmonella typhimurium invasion genes by environmental and regulatory factors is mediated by control of hilA expression. Mol Microbiol22:703–714 [CrossRef][PubMed]
    [Google Scholar]
  10. Baxter M. A., Fahlen T. F., Wilson R. L., Jones B. D.. ( 2003;). HilE interacts with HilD and negatively regulates hilA transcription and expression of the Salmonella enterica serovar Typhimurium invasive phenotype. Infect Immun71:1295–1305 [CrossRef][PubMed]
    [Google Scholar]
  11. Behlau I., Miller S. I.. ( 1993;). A PhoP-repressed gene promotes Salmonella typhimurium invasion of epithelial cells. J Bacteriol175:4475–4484[PubMed]
    [Google Scholar]
  12. Berggren R. E., Wunderlich A., Ziegler E., Schleicher M., Duke R. C., Looney D., Fang F. C.. ( 1995;). HIV gp120-specific cell-mediated immune responses in mice after oral immunization with recombinant Salmonella . J Acquir Immune Defic Syndr Hum Retrovirol10:489–495[PubMed][CrossRef]
    [Google Scholar]
  13. Boddicker J. D., Jones B. D.. ( 2004;). Lon protease activity causes down-regulation of Salmonella pathogenicity island 1 invasion gene expression after infection of epithelial cells. Infect Immun72:2002–2013 [CrossRef][PubMed]
    [Google Scholar]
  14. Boddicker J. D., Knosp B. M., Jones B. D.. ( 2003;). Transcription of the Salmonella invasion gene activator, hilA, requires HilD activation in the absence of negative regulators. J Bacteriol185:525–533 [CrossRef][PubMed]
    [Google Scholar]
  15. Bossemeyer D., Borchard A., Dosch D. C., Helmer G. C., Epstein W., Booth I. R., Bakker E. P.. ( 1989;). K+-transport protein TrkA of Escherichia coli is a peripheral membrane protein that requires other trk gene products for attachment to the cytoplasmic membrane. J Biol Chem264:16403–16410[PubMed]
    [Google Scholar]
  16. Chen Y. C., Chuang Y. C., Chang C. C., Jeang C. L., Chang M. C.. ( 2004;). A K+ uptake protein, TrkA, is required for serum, protamine, and polymyxin B resistance in Vibrio vulnificus . Infect Immun72:629–636 [CrossRef][PubMed]
    [Google Scholar]
  17. Cholo M. C., Boshoff H. I., Steel H. C., Cockeran R., Matlola N. M., Downing K. J., Mizrahi V., Anderson R.. ( 2006;). Effects of clofazimine on potassium uptake by a Trk-deletion mutant of Mycobacterium tuberculosis . J Antimicrob Chemother57:79–84 [CrossRef][PubMed]
    [Google Scholar]
  18. Darwin K. H., Miller V. L.. ( 1999;). InvF is required for expression of genes encoding proteins secreted by the SPI1 type III secretion apparatus in Salmonella typhimurium . J Bacteriol181:4949–4954[PubMed]
    [Google Scholar]
  19. Darwin K. H., Miller V. L.. ( 2000;). The putative invasion protein chaperone SicA acts together with InvF to activate the expression of Salmonella typhimurium virulence genes. Mol Microbiol35:949–960 [CrossRef][PubMed]
    [Google Scholar]
  20. Datsenko K. A., Wanner B. L.. ( 2000;). One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A97:6640–6645 [CrossRef][PubMed]
    [Google Scholar]
  21. Eichelberg K., Galán J. E.. ( 1999;). Differential regulation of Salmonella typhimurium type III secreted proteins by pathogenicity island 1 (SPI-1)-encoded transcriptional activators InvF and HilA. Infect Immun67:4099–4105[PubMed]
    [Google Scholar]
  22. Ellermeier C. D., Slauch J. M.. ( 2003;). RtsA and RtsB coordinately regulate expression of the invasion and flagellar genes in Salmonella enterica serovar Typhimurium. J Bacteriol185:5096–5108 [CrossRef][PubMed]
    [Google Scholar]
  23. Ellermeier C. D., Slauch J. M.. ( 2004;). RtsA coordinately regulates DsbA and the Salmonella pathogenicity island 1 type III secretion system. J Bacteriol186:68–79 [CrossRef][PubMed]
    [Google Scholar]
  24. Ellermeier J. R., Slauch J. M.. ( 2007;). Adaptation to the host environment: regulation of the SPI1 type III secretion system in Salmonella enterica serovar Typhimurium. Curr Opin Microbiol10:24–29 [CrossRef][PubMed]
    [Google Scholar]
  25. Epstein W.. ( 2003;). The roles and regulation of potassium in bacteria. Prog Nucleic Acid Res Mol Biol75:293–320 [CrossRef][PubMed]
    [Google Scholar]
  26. Fraser G. M., Hughes C.. ( 1999;). Swarming motility. Curr Opin Microbiol2:630–635 [CrossRef][PubMed]
    [Google Scholar]
  27. Frymier J. S., Reed T. D., Fletcher S. A., Csonka L. N.. ( 1997;). Characterization of transcriptional regulation of the kdp operon of Salmonella typhimurium . J Bacteriol179:3061–3063[PubMed]
    [Google Scholar]
  28. Gal-Mor O., Finlay B. B.. ( 2006;). Pathogenicity islands: a molecular toolbox for bacterial virulence. Cell Microbiol8:1707–1719 [CrossRef][PubMed]
    [Google Scholar]
  29. Golubeva Y. A., Sadik A. Y., Ellermeier J. R., Slauch J. M.. ( 2012;). Integrating global regulatory input into the Salmonella pathogenicity island 1 type III secretion system. Genetics190:79–90 [CrossRef][PubMed]
    [Google Scholar]
  30. Gong H., Vu G. P., Bai Y., Chan E., Wu R., Yang E., Liu F., Lu S.. ( 2011;). A Salmonella small non-coding RNA facilitates bacterial invasion and intracellular replication by modulating the expression of virulence factors. PLoS Pathog7:e1002120 [CrossRef][PubMed]
    [Google Scholar]
  31. Groisman E. A., Ochman H.. ( 1997;). How Salmonella became a pathogen. Trends Microbiol5:343–349 [CrossRef][PubMed]
    [Google Scholar]
  32. Ibarra J. A., Knodler L. A., Sturdevant D. E., Virtaneva K., Carmody A. B., Fischer E. R., Porcella S. F., Steele-Mortimer O.. ( 2010;). Induction of Salmonella pathogenicity island 1 under different growth conditions can affect Salmonella–host cell interactions in vitro . Microbiology156:1120–1133 [CrossRef][PubMed]
    [Google Scholar]
  33. Jepson M. A., Kenny B., Leard A. D.. ( 2001;). Role of sipA in the early stages of Salmonella typhimurium entry into epithelial cells. Cell Microbiol3:417–426 [CrossRef][PubMed]
    [Google Scholar]
  34. Jones B. D., Falkow S.. ( 1996;). Salmonellosis: host immune responses and bacterial virulence determinants. Annu Rev Immunol14:533–561 [CrossRef][PubMed]
    [Google Scholar]
  35. Journet L., Hughes K. T., Cornelis G. R.. ( 2005;). Type III secretion: a secretory pathway serving both motility and virulence (review). Mol Membr Biol22:41–50 [CrossRef][PubMed]
    [Google Scholar]
  36. Kaniga K., Trollinger D., Galán J. E.. ( 1995;). Identification of two targets of the type III protein secretion system encoded by the inv and spa loci of Salmonella typhimurium that have homology to the Shigella IpaD and IpaA proteins. J Bacteriol177:7078–7085[PubMed]
    [Google Scholar]
  37. Kem D. C., Trachewsky D.. ( 1983;). Potassium metabolism. Potassium: its Biologic Significance25–35 Whang R.. Boca Raton, FL: CRC Press;
    [Google Scholar]
  38. Komoriya K., Shibano N., Higano T., Azuma N., Yamaguchi S., Aizawa S. I.. ( 1999;). Flagellar proteins and type III-exported virulence factors are the predominant proteins secreted into the culture media of Salmonella typhimurium . Mol Microbiol34:767–779 [CrossRef][PubMed]
    [Google Scholar]
  39. Lawhon S. D., Frye J. G., Suyemoto M., Porwollik S., McClelland M., Altier C.. ( 2003;). Global regulation by CsrA in Salmonella typhimurium . Mol Microbiol48:1633–1645 [CrossRef][PubMed]
    [Google Scholar]
  40. Lin D., Rao C. V., Slauch J. M.. ( 2008;). The Salmonella SPI1 type three secretion system responds to periplasmic disulfide bond status via the flagellar apparatus and the RcsCDB system. J Bacteriol190:87–97 [CrossRef][PubMed]
    [Google Scholar]
  41. López-Garrido J., Casadesús J.. ( 2010;). Regulation of Salmonella enterica pathogenicity island 1 by DNA adenine methylation. Genetics184:637–649 [CrossRef][PubMed]
    [Google Scholar]
  42. Lu S., Manges A. R., Xu Y., Fang F. C., Riley L. W.. ( 1999;). Analysis of virulence of clinical isolates of Salmonella enteritidis in vivo and in vitro . Infect Immun67:5651–5657[PubMed]
    [Google Scholar]
  43. Lu S., Killoran P. B., Fang F. C., Riley L. W.. ( 2002;). The global regulator ArcA controls resistance to reactive nitrogen and oxygen intermediates in Salmonella enterica serovar Enteritidis. Infect Immun70:451–461 [CrossRef][PubMed]
    [Google Scholar]
  44. Lu S., Killoran P. B., Riley L. W.. ( 2003;). Association of Salmonella enterica serovar enteritidis yafD with resistance to chicken egg albumen. Infect Immun71:6734–6741 [CrossRef][PubMed]
    [Google Scholar]
  45. Maloy S. R., Stewart V. J., Taylor R. K.. ( 1996;). Genetic Analysis of Pathogenic Bacteria: a Laboratory Manual Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press;
    [Google Scholar]
  46. Miesenböck G., De Angelis D. A., Rothman J. E.. ( 1998;). Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature394:192–195 [CrossRef][PubMed]
    [Google Scholar]
  47. Mizusaki H., Takaya A., Yamamoto T., Aizawa S.. ( 2008;). Signal pathway in salt-activated expression of the Salmonella pathogenicity island 1 type III secretion system in Salmonella enterica serovar Typhimurium. J Bacteriol190:4624–4631 [CrossRef][PubMed]
    [Google Scholar]
  48. Murray P.. ( 2003;). Manual of Clinical Microbiology, 8th edn. Washington, DC: American Society for Microbiology;
    [Google Scholar]
  49. Paul K., Erhardt M., Hirano T., Blair D. F., Hughes K. T.. ( 2008;). Energy source of flagellar type III secretion. Nature451:489–492 [CrossRef][PubMed]
    [Google Scholar]
  50. Pegues D. A., Hantman M. J., Behlau I., Miller S. I.. ( 1995;). PhoP/PhoQ transcriptional repression of Salmonella typhimurium invasion genes: evidence for a role in protein secretion. Mol Microbiol17:169–181 [CrossRef][PubMed]
    [Google Scholar]
  51. Raffatellu M., Wilson R. P., Chessa D., Andrews-Polymenis H., Tran Q. T., Lawhon S., Khare S., Adams L. G., Bäumler A. J.. ( 2005;). SipA, SopA, SopB, SopD, and SopE2 contribute to Salmonella enterica serotype typhimurium invasion of epithelial cells. Infect Immun73:146–154 [CrossRef][PubMed]
    [Google Scholar]
  52. Rakeman J. L., Bonifield H. R., Miller S. I.. ( 1999;). A HilA-independent pathway to Salmonella typhimurium invasion gene transcription. J Bacteriol181:3096–3104[PubMed]
    [Google Scholar]
  53. Reed L. J., Muench H.. ( 1938;). A simple method of estimating fifty percent endpoints. Am J Hyg27:493–497
    [Google Scholar]
  54. Sambrook J., Russell D. W.. ( 2001;). Molecular Cloning: a Laboratory Manual, 3rd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  55. Schechter L. M., Lee C. A.. ( 2001;). AraC/XylS family members, HilC and HilD, directly bind and derepress the Salmonella typhimurium hilA promoter. Mol Microbiol40:1289–1299 [CrossRef][PubMed]
    [Google Scholar]
  56. Su J., Gong H., Lai J., Main A., Lu S.. ( 2009;). The potassium transporter Trk and external potassium modulate Salmonella enterica protein secretion and virulence. Infect Immun77:667–675 [CrossRef][PubMed]
    [Google Scholar]
  57. Thijs I. M., De Keersmaecker S. C., Fadda A., Engelen K., Zhao H., McClelland M., Marchal K., Vanderleyden J.. ( 2007;). Delineation of the Salmonella enterica serovar Typhimurium HilA regulon through genome-wide location and transcript analysis. J Bacteriol189:4587–4596 [CrossRef][PubMed]
    [Google Scholar]
  58. Trchounian A., Kobayashi H.. ( 1999;). Kup is the major K+ uptake system in Escherichia coli upon hyper-osmotic stress at a low pH. FEBS Lett447:144–148 [CrossRef][PubMed]
    [Google Scholar]
  59. Trchounian A., Kobayashi H.. ( 2000;). K+ uptake by fermenting Escherichia coli cells: pH dependent mode of the TrkA system operating. Biosci Rep20:277–288 [CrossRef][PubMed]
    [Google Scholar]
  60. Ueda A., Wood T. K.. ( 2008;). Potassium and sodium transporters of Pseudomonas aeruginosa regulate virulence to barley. Appl Microbiol Biotechnol79:843–858 [CrossRef][PubMed]
    [Google Scholar]
  61. Uzzau S., Figueroa-Bossi N., Rubino S., Bossi L.. ( 2001;). Epitope tagging of chromosomal genes in Salmonella . Proc Natl Acad Sci U S A98:15264–15269 [CrossRef][PubMed]
    [Google Scholar]
  62. Van Immerseel F., De Buck J., Boyen F., Bohez L., Pasmans F., Volf J., Sevcik M., Rychlik I., Haesebrouck F., Ducatelle R.. ( 2004a;). Medium-chain fatty acids decrease colonization and invasion through hilA suppression shortly after infection of chickens with Salmonella enterica serovar Enteritidis. Appl Environ Microbiol70:3582–3587 [CrossRef][PubMed]
    [Google Scholar]
  63. Van Immerseel F., De Buck J., De Smet I., Pasmans F., Haesebrouck F., Ducatelle R.. ( 2004b;). Interactions of butyric acid- and acetic acid-treated Salmonella with chicken primary cecal epithelial cells in vitro . Avian Dis48:384–391 [CrossRef][PubMed]
    [Google Scholar]
  64. Vandal O. H., Pierini L. M., Schnappinger D., Nathan C. F., Ehrt S.. ( 2008;). A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis . Nat Med14:849–854 [CrossRef][PubMed]
    [Google Scholar]
  65. Webber M. A., Bailey A. M., Blair J. M., Morgan E., Stevens M. P., Hinton J. C., Ivens A., Wain J., Piddock L. J.. ( 2009;). The global consequence of disruption of the AcrAB-TolC efflux pump in Salmonella enterica includes reduced expression of SPI-1 and other attributes required to infect the host. J Bacteriol191:4276–4285 [CrossRef][PubMed]
    [Google Scholar]
  66. Winter S. E., Winter M. G., Thiennimitr P., Gerriets V. A., Nuccio S. P., Rüssmann H., Bäumler A. J.. ( 2009;). The TviA auxiliary protein renders the Salmonella enterica serotype Typhi RcsB regulon responsive to changes in osmolarity. Mol Microbiol74:175–193 [CrossRef][PubMed]
    [Google Scholar]
  67. Xue T., You Y., Hong D., Sun H., Sun B.. ( 2011;). The Staphylococcus aureus KdpDE two-component system couples extracellular K+ sensing and Agr signaling to infection programming. Infect Immun79:2154–2167 [CrossRef][PubMed]
    [Google Scholar]
  68. Yan D., Ikeda T. P., Shauger A. E., Kustu S.. ( 1996;). Glutamate is required to maintain the steady-state potassium pool in Salmonella typhimurium . Proc Natl Acad Sci U S A93:6527–6531 [CrossRef][PubMed]
    [Google Scholar]
  69. Zakharyan E., Trchounian A.. ( 2001;). K+ influx by Kup in Escherichia coli is accompanied by a decrease in H+ efflux. FEMS Microbiol Lett204:61–64 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.068700-0
Loading
/content/journal/micro/10.1099/mic.0.068700-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error