Preferential Use of Central Metabolism Reveals a Nutritional Basis for Polymicrobial Infection
The human urinary tract is a leading source for polymicrobial infections and for the development of bacteremia and sepsis. Treating these potentially dangerous infections have recently become more challenging due to the appearance of uropathogenic strains that are resistant to the many of the most commonly prescribed antibiotics. The majority of urinary tract infections (UTI) are caused by Escherichia coli, while another bacterium, Proteus mirabilis, is more likely to cause catheter-associated UTI. Here, we report that uropathogenic E. coli and P. mirabilis have divergent nutritional requirements despite growing in the same host environment. This result indicates that E. coli and P. mirabilis do not directly compete for nutrients during UTI. Indeed, we found that persistence of both pathogens is enhanced when they co-colonize the host. This work represents an important step toward understanding the basic nutritional requirements for two major pathogens that cause UTI and shows how mixed infections can change these requirements. Understanding how bacteria grow during infections is fundamental to ultimately uncover new ways to combat increasingly drug-resistant bacterial infections.
Vyšlo v časopise:
Preferential Use of Central Metabolism Reveals a Nutritional Basis for Polymicrobial Infection. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004601
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004601
Souhrn
The human urinary tract is a leading source for polymicrobial infections and for the development of bacteremia and sepsis. Treating these potentially dangerous infections have recently become more challenging due to the appearance of uropathogenic strains that are resistant to the many of the most commonly prescribed antibiotics. The majority of urinary tract infections (UTI) are caused by Escherichia coli, while another bacterium, Proteus mirabilis, is more likely to cause catheter-associated UTI. Here, we report that uropathogenic E. coli and P. mirabilis have divergent nutritional requirements despite growing in the same host environment. This result indicates that E. coli and P. mirabilis do not directly compete for nutrients during UTI. Indeed, we found that persistence of both pathogens is enhanced when they co-colonize the host. This work represents an important step toward understanding the basic nutritional requirements for two major pathogens that cause UTI and shows how mixed infections can change these requirements. Understanding how bacteria grow during infections is fundamental to ultimately uncover new ways to combat increasingly drug-resistant bacterial infections.
Zdroje
1. EisenreichW, DandekarT, HeesemannJ, GoebelW (2010) Carbon metabolism of intracellular bacterial pathogens and possible links to virulence. Nat Rev Microbiol 8: 401–412.
2. SomervilleGA, ProctorRA (2009) At the crossroads of bacterial metabolism and virulence factor synthesis in Staphylococci. Microbiol Mol Biol Rev 73: 233–248.
3. PoncetS, MilohanicE, MazeA, Nait AbdallahJ, AkeF, et al. (2009) Correlations between carbon metabolism and virulence in bacteria. Contrib Microbiol 16: 88–102.
4. RohmerL, HocquetD, MillerSI (2011) Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis. Trends Microbiol 19: 341–348.
5. SmithH (2000) Questions about the behaviour of bacterial pathogens in vivo. Philos Trans R Soc Lond B Biol Sci 355: 551–564.
6. AlteriCJ, MobleyHL (2012) Escherichia coli physiology and metabolism dictates adaptation to diverse host microenvironments. Curr Opin Microbiol 15: 3–9.
7. FreterR, BricknerH, BotneyM, ClevenD, ArankiA (1983) Mechanisms that control bacterial populations in continuous-flow culture models of mouse large intestinal flora. Infect Immun 39: 676–685.
8. AlteriCJ, SmithSN, MobleyHL (2009) Fitness of Escherichia coli during urinary tract infection requires gluconeogenesis and the TCA cycle. PLoS Pathog 5: e1000448.
9. FabichAJ, JonesSA, ChowdhuryFZ, CernosekA, AndersonA, et al. (2008) Comparison of carbon nutrition for pathogenic and commensal Escherichia coli strains in the mouse intestine. Infect Immun 76: 1143–1152.
10. WinterSE, ThiennimitrP, WinterMG, ButlerBP, HusebyDL, et al. (2010) Gut inflammation provides a respiratory electron acceptor for Salmonella. Nature 467: 426–429.
11. AlteriCJ, LindnerJR, ReissDJ, SmithSN, MobleyHL (2011) The broadly conserved regulator PhoP links pathogen virulence and membrane potential in Escherichia coli. Mol Microbiol 82: 145–163.
12. EylertE, ScharJ, MertinsS, StollR, BacherA, et al. (2008) Carbon metabolism of Listeria monocytogenes growing inside macrophages. Mol Microbiol 69: 1008–1017.
13. JosephB, MertinsS, StollR, ScharJ, UmeshaKR, et al. (2008) Glycerol metabolism and PrfA activity in Listeria monocytogenes. J Bacteriol 190: 5412–5430.
14. JosephB, PrzybillaK, StuhlerC, SchauerK, SlaghuisJ, et al. (2006) Identification of Listeria monocytogenes genes contributing to intracellular replication by expression profiling and mutant screening. J Bacteriol 188: 556–568.
15. ChatterjeeSS, HossainH, OttenS, KuenneC, KuchminaK, et al. (2006) Intracellular gene expression profile of Listeria monocytogenes. Infect Immun 74: 1323–1338.
16. StollR, GoebelW (2010) The major PEP-phosphotransferase systems (PTSs) for glucose, mannose and cellobiose of Listeria monocytogenes, and their significance for extra- and intracellular growth. Microbiology 156: 1069–1083.
17. LucchiniS, LiuH, JinQ, HintonJC, YuJ (2005) Transcriptional adaptation of Shigella flexneri during infection of macrophages and epithelial cells: insights into the strategies of a cytosolic bacterial pathogen. Infect Immun 73: 88–102.
18. NoriegaFR, LosonskyG, LauderbaughC, LiaoFM, WangJY, et al. (1996) Engineered deltaguaB-A deltavirG Shigella flexneri 2a strain CVD 1205: construction, safety, immunogenicity, and potential efficacy as a mucosal vaccine. Infect Immun 64: 3055–3061.
19. CersiniA, MartinoMC, MartiniI, RossiG, BernardiniML (2003) Analysis of virulence and inflammatory potential of Shigella flexneri purine biosynthesis mutants. Infect Immun 71: 7002–7013.
20. SchnappingerD, EhrtS, VoskuilMI, LiuY, ManganJA, et al. (2003) Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment. J Exp Med 198: 693–704.
21. McKinneyJD, Honer zu BentrupK, Munoz-EliasEJ, MiczakA, ChenB, et al. (2000) Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406: 735–738.
22. Munoz-EliasEJ, UptonAM, CherianJ, McKinneyJD (2006) Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. Mol Microbiol 60: 1109–1122.
23. Munoz-EliasEJ, McKinneyJD (2005) Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Nat Med 11: 638–644.
24. Tchawa YimgaM, LeathamMP, AllenJH, LauxDC, ConwayT, et al. (2006) Role of gluconeogenesis and the tricarboxylic acid cycle in the virulence of Salmonella enterica serovar Typhimurium in BALB/c mice. Infect Immun 74: 1130–1140.
25. Mercado-LuboR, GaugerEJ, LeathamMP, ConwayT, CohenPS (2008) A Salmonella enterica serovar typhimurium succinate dehydrogenase/fumarate reductase double mutant is avirulent and immunogenic in BALB/c mice. Infect Immun 76: 1128–1134.
26. Mercado-LuboR, LeathamMP, ConwayT, CohenPS (2009) Salmonella enterica serovar Typhimurium mutants unable to convert malate to pyruvate and oxaloacetate are avirulent and immunogenic in BALB/c mice. Infect Immun 77: 1397–1405.
27. BowdenSD, RowleyG, HintonJC, ThompsonA (2009) Glucose and glycolysis are required for the successful infection of macrophages and mice by Salmonella enterica serovar typhimurium. Infect Immun 77: 3117–3126.
28. ChangDE, SmalleyDJ, TuckerDL, LeathamMP, NorrisWE, et al. (2004) Carbon nutrition of Escherichia coli in the mouse intestine. Proc Natl Acad Sci U S A 101: 7427–7432.
29. MirandaRL, ConwayT, LeathamMP, ChangDE, NorrisWE, et al. (2004) Glycolytic and gluconeogenic growth of Escherichia coli O157: H7 (EDL933) and E. coli K-12 (MG1655) in the mouse intestine. Infect Immun 72: 1666–1676.
30. AnforaAT, HalladinDK, HaugenBJ, WelchRA (2008) Uropathogenic Escherichia coli CFT073 is adapted to acetatogenic growth but does not require acetate during murine urinary tract infection. Infect Immun 76: 5760–5767.
31. AnforaAT, HaugenBJ, RoeschP, RedfordP, WelchRA (2007) Roles of serine accumulation and catabolism in the colonization of the murine urinary tract by Escherichia coli CFT073. Infect Immun 75: 5298–5304.
32. BurallLS, HarroJM, LiX, LockatellCV, HimpslSD, et al. (2004) Proteus mirabilis genes that contribute to pathogenesis of urinary tract infection: identification of 25 signature-tagged mutants attenuated at least 100-fold. Infect Immun 72: 2922–2938.
33. HimpslSD, LockatellCV, HebelJR, JohnsonDE, MobleyHL (2008) Identification of virulence determinants in uropathogenic Proteus mirabilis using signature-tagged mutagenesis. J Med Microbiol 57: 1068–1078.
34. HaganEC, LloydAL, RaskoDA, FaerberGJ, MobleyHL (2010) Escherichia coli global gene expression in urine from women with urinary tract infection. PLoS Pathog 6: e1001187.
35. SnyderJA, HaugenBJ, BucklesEL, LockatellCV, JohnsonDE, et al. (2004) Transcriptome of uropathogenic Escherichia coli during urinary tract infection. Infect Immun 72: 6373–6381.
36. PearsonMM, YepA, SmithSN, MobleyHL (2011) Transcriptome of Proteus mirabilis in the Murine Urinary Tract: Virulence and Nitrogen Assimilation Gene Expression. Infect Immun 79: 2619–2631.
37. MobleyHL, GreenDM, TrifillisAL, JohnsonDE, ChippendaleGR, et al. (1990) Pyelonephritogenic Escherichia coli and killing of cultured human renal proximal tubular epithelial cells: role of hemolysin in some strains. Infect Immun 58: 1281–1289.
38. WelchRA, BurlandV, PlunkettG3rd, RedfordP, RoeschP, et al. (2002) Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc Natl Acad Sci USA 99: 17020–17024.
39. HagbergL, EngbergI, FreterR, LamJ, OllingS, et al. (1983) Ascending, unobstructed urinary tract infection in mice caused by pyelonephritogenic Escherichia coli of human origin. Infect Immun 40: 273–283.
40. BrooksT, KeevilCW (1997) A simple artificial urine for the growth of urinary pathogens. Lett Appl Microbiol 24: 203–206.
41. SprengerGA (1995) Genetics of pentose-phosphate pathway enzymes of Escherichia coli K-12. Arch Microbiol 164: 324–330.
42. HadjifrangiskouM, KostakiotiM, ChenSL, HendersonJP, GreeneSE, et al. (2011) A central metabolic circuit controlled by QseC in pathogenic Escherichia coli. Mol Microbiol 80: 1516–1529.
43. RoeschPL, RedfordP, BatcheletS, MoritzRL, PellettS, et al. (2003) Uropathogenic Escherichia coli use d-serine deaminase to modulate infection of the murine urinary tract. Mol Microbiol 49: 55–67.
44. CaiW, WannemuehlerY, Dell'annaG, NicholsonB, BarbieriNL, et al. (2013) A novel two-component signaling system facilitates uropathogenic Escherichia coli's ability to exploit abundant host metabolites. PLoS Pathog 9: e1003428.
45. JonesBD, LockatellCV, JohnsonDE, WarrenJW, MobleyHL (1990) Construction of a urease-negative mutant of Proteus mirabilis: analysis of virulence in a mouse model of ascending urinary tract infection. Infect Immun 58: 1120–1123.
46. JonesBD, MobleyHL (1988) Proteus mirabilis urease: genetic organization, regulation, and expression of structural genes. J Bacteriol 170: 3342–3349.
47. MaoXJ, HuoYX, BuckM, KolbA, WangYP (2007) Interplay between CRP-cAMP and PII-Ntr systems forms novel regulatory network between carbon metabolism and nitrogen assimilation in Escherichia coli. Nucleic Acids Res 35: 1432–1440.
48. SchumacherJ, BehrendsV, PanZ, BrownDR, HeydenreichF, et al. (2013) Nitrogen and carbon status are integrated at the transcriptional level by the nitrogen regulator NtrC in vivo. MBio 4: e00881–00813.
49. De LayN, GottesmanS (2009) The Crp-activated small noncoding regulatory RNA CyaR (RyeE) links nutritional status to group behavior. J Bacteriol 191: 461–476.
50. MulveyMA, Lopez-BoadoYS, WilsonCL, RothR, ParksWC, et al. (1998) Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science 282: 1494–1497.
51. MulveyMA, SchillingJD, MartinezJJ, HultgrenSJ (2000) Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia coli and innate host defenses. Proc Natl Acad Sci U S A 97: 8829–8835.
52. AllisonC, ColemanN, JonesPL, HughesC (1992) Ability of Proteus mirabilis to invade human urothelial cells is coupled to motility and swarming differentiation. Infect Immun 60: 4740–4746.
53. MobleyHL, BelasR, LockatellV, ChippendaleG, TrifillisAL, et al. (1996) Construction of a flagellum-negative mutant of Proteus mirabilis: effect on internalization by human renal epithelial cells and virulence in a mouse model of ascending urinary tract infection. Infect Immun 64: 5332–5340.
54. UndenG, BongaertsJ (1997) Alternative respiratory pathways of Escherichia coli: energetics and transcriptional regulation in response to electron acceptors. Biochim Biophys Acta 1320: 217–234.
55. BrogdenKA, GuthmillerJM, TaylorCE (2005) Human polymicrobial infections. Lancet 365: 253–255.
56. WarrenJW, TenneyJH, HoopesJM, MuncieHL, AnthonyWC (1982) A prospective microbiologic study of bacteriuria in patients with chronic indwelling urethral catheters. J Infect Dis 146: 719–723.
57. SaverinoD, SchitoAM, ManniniA, PencoS, BassiAM, et al. (2011) Quinolone/fluoroquinolone susceptibility in Escherichia coli correlates with human polymicrobial bacteriuria and with in vitro interleukine-8 suppression. FEMS Immunol Med Microbiol 61: 84–93.
58. CroxallG, WestonV, JosephS, ManningG, CheethamP, et al. (2011) Increased human pathogenic potential of Escherichia coli from polymicrobial urinary tract infections in comparison to isolates from monomicrobial culture samples. J Med Microbiol 60: 102–109.
59. MobleyHL, WarrenJW (1987) Urease-positive bacteriuria and obstruction of long-term urinary catheters. J Clin Microbiol 25: 2216–2217.
60. NeidhardtFC, BlochPL, SmithDF (1974) Culture medium for enterobacteria. J Bacteriol 119: 736–747.
61. BelasR, ErskineD, FlahertyD (1991) Transposon mutagenesis in Proteus mirabilis. J Bacteriol 173: 6289–6293.
62. DatsenkoKA, WannerBL (2000) One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97: 6640–6645.
63. GalenJE, NairJ, WangJY, WassermanSS, TannerMK, et al. (1999) Optimization of plasmid maintenance in the attenuated live vector vaccine strain Salmonella typhi CVD 908-htrA. Infect Immun 67: 6424–6433.
64. LaneMC, AlteriCJ, SmithSN, MobleyHL (2007) Expression of flagella is coincident with uropathogenic Escherichia coli ascension to the upper urinary tract. Proc Natl Acad Sci U S A 104: 16669–16674.
65. JohnsonDE, LockatellCV, Hall-CraigsM, MobleyHL, WarrenJW (1987) Uropathogenicity in rats and mice of Providencia stuartii from long-term catheterized patients. J Urol 138: 632–635.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2015 Číslo 1
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Infections in Humans and Animals: Pathophysiology, Detection, and Treatment
- The Phylogenetically-Related Pattern Recognition Receptors EFR and XA21 Recruit Similar Immune Signaling Components in Monocots and Dicots
- Specificity and Dynamics of Effector and Memory CD8 T Cell Responses in Human Tick-Borne Encephalitis Virus Infection
- Viral Activation of MK2-hsp27-p115RhoGEF-RhoA Signaling Axis Causes Cytoskeletal Rearrangements, P-body Disruption and ARE-mRNA Stabilization