Home LiteratureArticle Details
PMID: 18482721 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Origins and virulence mechanisms of uropathogenic Escherichia coli.

Experimental and molecular pathology ·Vol. 85 ·No. 1 ·2008-08-00 ·Pages 11-9

Wiles TJ, Kulesus RR, Mulvey MA

Abstract

Strains of uropathogenic E. coli (UPEC) are the primary cause of urinary tract infections, including both cystitis and pyelonephritis. These bacteria have evolved a multitude of virulence factors and strategies that facilitate bacterial growth and persistence within the adverse settings of the host urinary tract. Expression of adhesive organelles like type 1 and P pili allow UPEC to bind and invade host cells and tissues within the urinary tract while expression of iron-chelating factors (siderophores) enable UPEC to pilfer host iron stores. Deployment of an array of toxins, including hemolysin and cytotoxic necrotizing factor 1, provide UPEC with the means to inflict extensive tissue damage, facilitating bacterial dissemination as well as releasing host nutrients and disabling immune effector cells. These toxins also have the capacity to modulate, in more subtle ways, host signaling pathways affecting myriad processes, including inflammatory responses, host cell survival, and cytoskeletal dynamics. Here, we discuss the mechanisms by which these and other virulence factors promote UPEC survival and growth within the urinary tract. Comparisons are also made between UPEC and other strains of extraintestinal pathogenic E. coli that, although closely related to UPEC, are distinct in their abilities to colonize the host and cause disease.

MeSH Terms
Escherichia coli/genetics,immunology,pathogenicity Humans Urinary Tract Infections/microbiology Virulence/genetics Virulence Factors/genetics,metabolism
Chemicals
Virulence Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wiles Travis J
Division of Cell Biology and Immunology, Pathology Department, University of Utah, Salt Lake City, Utah 84112-0565, USA.
Kulesus Richard R
Mulvey Matthew A
References (115)
115 references, click to expand
  1. Pathogenic Escherichia coli.
    Nat Rev Microbiol. 2004 Feb;2(2):123-40 PMID: 15040260
  2. Virulence factors in Escherichia coli urinary tract infection.
    Clin Microbiol Rev. 1991 Jan;4(1):80-128 PMID: 1672263
  3. Switches, cross-talk and memory in Escherichia coli adherence.
    J Med Microbiol. 2004 Jul;53(Pt 7):585-593 PMID: 15184527
  4. The globoseries glycosphingolipid sialosyl galactosyl globoside is found in urinary tract tissues and is a preferred binding receptor In vitro for uropathogenic Escherichia coli expressing pap-encoded adhesins.
    Infect Immun. 1998 Aug;66(8):3856-61 PMID: 9673272
  5. Loss of regulatory protein RfaH attenuates virulence of uropathogenic Escherichia coli.
    Infect Immun. 2002 Aug;70(8):4406-13 PMID: 12117951
  6. Calcium is required for binding of Escherichia coli hemolysin (HlyA) to erythrocyte membranes.
    Infect Immun. 1990 Jun;58(6):1951-8 PMID: 2187814
  7. Role of P-fimbrial-mediated adherence in pyelonephritis and persistence of uropathogenic Escherichia coli (UPEC) in the mammalian kidney.
    Kidney Int. 2007 Jul;72(1):19-25 PMID: 17396114
  8. How pathogenic bacteria evade mammalian sabotage in the battle for iron.
    Nat Chem Biol. 2006 Mar;2(3):132-8 PMID: 16485005
  9. Pathogenicity islands and the evolution of microbes.
    Annu Rev Microbiol. 2000;54:641-79 PMID: 11018140
  10. Domains of Escherichia coli hemolysin (HlyA) involved in binding of calcium and erythrocyte membranes.
    Infect Immun. 1990 Jun;58(6):1959-64 PMID: 2187815
  11. Binding specificities of wild-type and cloned Escherichia coli strains that recognize globo-A.
    Infect Immun. 1989 Nov;57(11):3389-94 PMID: 2572551
  12. Alpha-haemolysin of uropathogenic E. coli induces Ca2+ oscillations in renal epithelial cells.
    Nature. 2000 Jun 8;405(6787):694-7 PMID: 10864327
  13. The structure of salmochelins: C-glucosylated enterobactins of Salmonella enterica.
    Biometals. 2004 Aug;17(4):471-81 PMID: 15259369
  14. Characterizing the APEC pathotype.
    Vet Res. 2005 Mar-Apr;36(2):241-56 PMID: 15720976
  15. The hemolysin of Escherichia coli.
    Eur J Epidemiol. 1988 Jun;4(2):135-43 PMID: 3042445
  16. Calcium signalling during cell interactions with bacterial pathogens.
    Biol Cell. 2004 Feb;96(1):93-101 PMID: 15093131
  17. A novel pathogenicity island integrated adjacent to the thrW tRNA gene of avian pathogenic Escherichia coli encodes a vacuolating autotransporter toxin.
    Infect Immun. 2003 Sep;71(9):5087-96 PMID: 12933851
  18. Comparison of Escherichia coli isolates implicated in human urinary tract infection and avian colibacillosis.
    Microbiology (Reading). 2005 Jun;151(Pt 6):2097-2110 PMID: 15942016
  19. Pathogenicity islands of virulent bacteria: structure, function and impact on microbial evolution.
    Mol Microbiol. 1997 Mar;23(6):1089-97 PMID: 9106201
  20. Rho GTPase-activating bacterial toxins: from bacterial virulence regulation to eukaryotic cell biology.
    FEMS Microbiol Rev. 2007 Sep;31(5):515-34 PMID: 17680807
  21. The genome sequence of avian pathogenic Escherichia coli strain O1:K1:H7 shares strong similarities with human extraintestinal pathogenic E. coli genomes.
    J Bacteriol. 2007 Apr;189(8):3228-36 PMID: 17293413
  22. Cytotoxic necrotizing factor type 1 delivered by outer membrane vesicles of uropathogenic Escherichia coli attenuates polymorphonuclear leukocyte antimicrobial activity and chemotaxis.
    Infect Immun. 2006 Aug;74(8):4401-8 PMID: 16861625
  23. Type 1, P and S fimbriae, and afimbrial adhesin I are not essential for uropathogenic Escherichia coli to adhere to and invade bladder epithelial cells.
    FEMS Immunol Med Microbiol. 2002 Mar 25;33(1):23-6 PMID: 11985964
  24. Commensal bacteria in the gut: learning who our friends are.
    Curr Opin Gastroenterol. 2004 Nov;20(6):565-71 PMID: 15703684
  25. Role of Escherichia coli K capsular antigens during complement activation, C3 fixation, and opsonization.
    Infect Immun. 1979 Aug;25(2):603-9 PMID: 385502
  26. Common and specific genomic sequences of avian and human extraintestinal pathogenic Escherichia coli as determined by genomic subtractive hybridization.
    BMC Microbiol. 2007 Aug 30;7:81 PMID: 17760980
  27. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells.
    EMBO J. 2000 Jun 15;19(12):2803-12 PMID: 10856226
  28. [Avian pathogenic Escherichia coli (APEC)].
    Berl Munch Tierarztl Wochenschr. 2003 Sep-Oct;116(9-10):381-95 PMID: 14526468
  29. Salmochelins, siderophores of Salmonella enterica and uropathogenic Escherichia coli strains, are recognized by the outer membrane receptor IroN.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3677-82 PMID: 12655053
  30. Rho GTPases in cell biology.
    Nature. 2002 Dec 12;420(6916):629-35 PMID: 12478284
  31. Avian pathogenic, uropathogenic, and newborn meningitis-causing Escherichia coli: how closely related are they?
    Int J Med Microbiol. 2007 Jun;297(3):163-76 PMID: 17374506
  32. Integrin-mediated host cell invasion by type 1-piliated uropathogenic Escherichia coli.
    PLoS Pathog. 2007 Jul;3(7):e100 PMID: 17630833
  33. Mutation of the gene encoding cytotoxic necrotizing factor type 1 (cnf(1)) attenuates the virulence of uropathogenic Escherichia coli.
    Infect Immun. 2001 Jun;69(6):3954-64 PMID: 11349064
  34. Acquisition of avian pathogenic Escherichia coli plasmids by a commensal E. coli isolate enhances its abilities to kill chicken embryos, grow in human urine, and colonize the murine kidney.
    Infect Immun. 2006 Nov;74(11):6287-92 PMID: 16954398
  35. Uropathogenic Escherichia coli are more likely than commensal E. coli to be shared between heterosexual sex partners.
    Am J Epidemiol. 2002 Dec 15;156(12):1133-40 PMID: 12480658
  36. The asymptomatic bacteriuria Escherichia coli strain 83972 outcompetes uropathogenic E. coli strains in human urine.
    Infect Immun. 2006 Jan;74(1):615-24 PMID: 16369018
  37. Uroplakin Ia is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding.
    J Cell Sci. 2001 Nov;114(Pt 22):4095-103 PMID: 11739641
  38. Covert operations of uropathogenic Escherichia coli within the urinary tract.
    Traffic. 2005 Jan;6(1):18-31 PMID: 15569242
  39. Urinary tract infection prophylaxis using Escherichia coli 83972 in spinal cord injured patients.
    J Urol. 2000 Mar;163(3):872-7 PMID: 10687996
  40. Uropathogenic Escherichia coli flagella aid in efficient urinary tract colonization.
    Infect Immun. 2005 Nov;73(11):7657-68 PMID: 16239570
  41. Cell biology: iron thievery.
    Nature. 2004 Dec 16;432(7019):811-3 PMID: 15602535
  42. Engagement of integrins as a cellular route of invasion by bacterial pathogens.
    Vet J. 2007 May;173(3):482-91 PMID: 16546423
  43. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition.
    Mol Cell. 2002 Nov;10(5):1033-43 PMID: 12453412
  44. Molecular basis of commensalism in the urinary tract: low virulence or virulence attenuation?
    Infect Immun. 2008 Feb;76(2):695-703 PMID: 18039831
  45. Iron metabolism at the host pathogen interface: lipocalin 2 and the pathogen-associated iroA gene cluster.
    Int J Biochem Cell Biol. 2007;39(10):1776-80 PMID: 17714976
  46. Role of the lipopolysaccharide-CD14 complex for the activity of hemolysin from uropathogenic Escherichia coli.
    Infect Immun. 2007 Feb;75(2):997-1004 PMID: 17101668
  47. Virulence properties of Escherichia coli 83972, a prototype strain associated with asymptomatic bacteriuria.
    Infect Immun. 1999 Jan;67(1):429-32 PMID: 9864249
  48. Special delivery: vesicle trafficking in prokaryotes.
    Mol Microbiol. 2006 Aug;61(4):839-46 PMID: 16879642
  49. Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach.
    Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5977-82 PMID: 16585510
  50. Host-specificity of uropathogenic Escherichia coli depends on differences in binding specificity to Gal alpha 1-4Gal-containing isoreceptors.
    EMBO J. 1990 Jun;9(6):2001-10 PMID: 1693334
  51. TLR4-initiated and cAMP-mediated abrogation of bacterial invasion of the bladder.
    Cell Host Microbe. 2007 Jun 14;1(4):287-98 PMID: 17710226
  52. Combined multilocus sequence typing and O serogrouping distinguishes Escherichia coli subtypes associated with infant urosepsis and/or meningitis.
    J Infect Dis. 2007 Jul 15;196(2):297-303 PMID: 17570118
  53. pap-2-encoded fimbriae adhere to the P blood group-related glycosphingolipid stage-specific embryonic antigen 4 in the human kidney.
    Infect Immun. 1990 Dec;58(12):4055-62 PMID: 1979319
  54. Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia coli and innate host defenses.
    Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8829-35 PMID: 10922042
  55. Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli.
    Science. 1998 Nov 20;282(5393):1494-7 PMID: 9822381
  56. Structural basis of tropism of Escherichia coli to the bladder during urinary tract infection.
    Mol Microbiol. 2002 May;44(4):903-15 PMID: 12010488
  57. Interaction of the bacterial protein toxin alpha-haemolysin with model membranes: protein binding does not always lead to lytic activity.
    FEBS Lett. 1995 Sep 11;371(3):303-6 PMID: 7556616
  58. Pathogenicity islands: a molecular toolbox for bacterial virulence.
    Cell Microbiol. 2006 Nov;8(11):1707-19 PMID: 16939533
  59. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs.
    Dis Mon. 2003 Feb;49(2):53-70 PMID: 12601337
  60. Role of the capsule and the O antigen in resistance of O18:K1 Escherichia coli to complement-mediated killing.
    Infect Immun. 1983 Dec;42(3):907-13 PMID: 6196296
  61. How to become a uropathogen: comparative genomic analysis of extraintestinal pathogenic Escherichia coli strains.
    Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12879-84 PMID: 16912116
  62. The structures of Escherichia coli O-polysaccharide antigens.
    FEMS Microbiol Rev. 2006 May;30(3):382-403 PMID: 16594963
  63. Bacterial iron homeostasis.
    FEMS Microbiol Rev. 2003 Jun;27(2-3):215-37 PMID: 12829269
  64. Establishment of a persistent Escherichia coli reservoir during the acute phase of a bladder infection.
    Infect Immun. 2001 Jul;69(7):4572-9 PMID: 11402001
  65. Defining genomic islands and uropathogen-specific genes in uropathogenic Escherichia coli.
    J Bacteriol. 2007 May;189(9):3532-46 PMID: 17351047
  66. Widespread distribution of urinary tract infections caused by a multidrug-resistant Escherichia coli clonal group.
    N Engl J Med. 2001 Oct 4;345(14):1007-13 PMID: 11586952
  67. Expression of flagella is coincident with uropathogenic Escherichia coli ascension to the upper urinary tract.
    Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16669-74 PMID: 17925449
  68. Mellowing out: adaptation to commensalism by Escherichia coli asymptomatic bacteriuria strain 83972.
    Infect Immun. 2007 Aug;75(8):3688-95 PMID: 17502385
  69. Why Escherichia coli alpha-hemolysin induces calcium oscillations in mammalian cells--the pore is on its own.
    FASEB J. 2006 May;20(7):973-5 PMID: 16597673
  70. Biofilm formation by asymptomatic and virulent urinary tract infectious Escherichia coli strains.
    FEMS Microbiol Lett. 2007 Feb;267(1):30-7 PMID: 17166230
  71. Coordinate expression of fimbriae in uropathogenic Escherichia coli.
    Infect Immun. 2005 Nov;73(11):7588-96 PMID: 16239562
  72. Type V protein secretion pathway: the autotransporter story.
    Microbiol Mol Biol Rev. 2004 Dec;68(4):692-744 PMID: 15590781
  73. Extraintestinal pathogenic Escherichia coli strains of avian and human origin: link between phylogenetic relationships and common virulence patterns.
    J Clin Microbiol. 2007 Oct;45(10):3366-76 PMID: 17652485
  74. Effect of Escherichia coli alpha-hemolysin on human peripheral leukocyte function in vitro.
    Infect Immun. 1982 Sep;37(3):966-74 PMID: 6752033
  75. Detection of intracellular bacterial communities in human urinary tract infection.
    PLoS Med. 2007 Dec;4(12):e329 PMID: 18092884
  76. Epithelial cells are sensitive detectors of bacterial pore-forming toxins.
    J Biol Chem. 2006 May 5;281(18):12994-8 PMID: 16520379
  77. Actin-gated intracellular growth and resurgence of uropathogenic Escherichia coli.
    Cell Microbiol. 2006 Apr;8(4):704-17 PMID: 16548895
  78. Molecular characterization of the Escherichia coli asymptomatic bacteriuria strain 83972: the taming of a pathogen.
    Infect Immun. 2006 Jan;74(1):781-5 PMID: 16369040
  79. Role of motility in the colonization of uropathogenic Escherichia coli in the urinary tract.
    Infect Immun. 2005 Nov;73(11):7644-56 PMID: 16239569
  80. Autotransporter-encoding sequences are phylogenetically distributed among Escherichia coli clinical isolates and reference strains.
    Appl Environ Microbiol. 2007 Mar;73(5):1553-62 PMID: 17220264
  81. Cytotoxic necrotizing factor type 1 of uropathogenic Escherichia coli kills cultured human uroepithelial 5637 cells by an apoptotic mechanism.
    Infect Immun. 2000 Oct;68(10):5869-80 PMID: 10992497
  82. Regulatory cross-talk between adhesin operons in Escherichia coli: inhibition of type 1 fimbriae expression by the PapB protein.
    EMBO J. 2000 Apr 3;19(7):1450-7 PMID: 10747013
  83. Host specificity of septicemic Escherichia coli: human and avian pathogens.
    Curr Opin Microbiol. 2006 Feb;9(1):28-32 PMID: 16384724
  84. Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9827-32 PMID: 8790416
  85. Contribution of capsular polysaccharide and surface properties to virulence of Escherichia coli K1.
    Infect Immun. 1987 Nov;55(11):2662-8 PMID: 3312006
  86. Demonstration of regulatory cross-talk between P fimbriae and type 1 fimbriae in uropathogenic Escherichia coli.
    Microbiology (Reading). 2006 Apr;152(Pt 4):1143-1153 PMID: 16549677
  87. Regulation of P-fimbrial phase variation frequencies in Escherichia coli CFT073.
    Infect Immun. 2007 Jul;75(7):3325-34 PMID: 17452474
  88. Intracellular bacterial biofilm-like pods in urinary tract infections.
    Science. 2003 Jul 4;301(5629):105-7 PMID: 12843396
  89. Functional genomic studies of uropathogenic Escherichia coli and host urothelial cells when intracellular bacterial communities are assembled.
    J Biol Chem. 2007 Jul 20;282(29):21259-67 PMID: 17504765
  90. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron.
    Nature. 2004 Dec 16;432(7019):917-21 PMID: 15531878
  91. Escherichia coli mediated urinary tract infections: are there distinct uropathogenic E. coli (UPEC) pathotypes?
    FEMS Microbiol Lett. 2005 Nov 15;252(2):183-90 PMID: 16165319
  92. CNF1 exploits the ubiquitin-proteasome machinery to restrict Rho GTPase activation for bacterial host cell invasion.
    Cell. 2002 Nov 15;111(4):553-64 PMID: 12437928
  93. The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2.
    Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16502-7 PMID: 17060628
  94. Asymptomatic bacteriuria Escherichia coli strain 83972 carries mutations in the foc locus and is unable to express F1C fimbriae.
    Microbiology (Reading). 2006 Jun;152(Pt 6):1799-1806 PMID: 16735742
  95. Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili.
    Cell Microbiol. 2007 Sep;9(9):2230-41 PMID: 17490405
  96. Protease activity, secretion, cell entry, cytotoxicity, and cellular targets of secreted autotransporter toxin of uropathogenic Escherichia coli.
    Infect Immun. 2006 Nov;74(11):6124-34 PMID: 16954394
  97. Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination.
    Science. 1997 Apr 25;276(5312):607-11 PMID: 9110982
  98. Active cytotoxic necrotizing factor 1 associated with outer membrane vesicles from uropathogenic Escherichia coli.
    Infect Immun. 2006 Apr;74(4):2022-30 PMID: 16552031
  99. Chromosomal restriction fragment length polymorphism analysis of Escherichia coli strains causing recurrent urinary tract infections in young women.
    J Infect Dis. 1995 Aug;172(2):440-5 PMID: 7622887
  100. Inactivation of host Akt/protein kinase B signaling by bacterial pore-forming toxins.
    Mol Biol Cell. 2008 Apr;19(4):1427-38 PMID: 18234841
  101. Concurrent fecal colonization with extraintestinal pathogenic Escherichia coli in a homosexual man with recurrent urinary tract infection and in his male sex partner.
    Clin Infect Dis. 2002 Sep 15;35(6):E65-8 PMID: 12203187
  102. Proposal for a new inclusive designation for extraintestinal pathogenic isolates of Escherichia coli: ExPEC.
    J Infect Dis. 2000 May;181(5):1753-4 PMID: 10823778
  103. Escherichia coli K1's capsule is a barrier to bacteriophage T7.
    Appl Environ Microbiol. 2005 Aug;71(8):4872-4 PMID: 16085886
  104. Cytotoxic necrotizing factor type 1 production by uropathogenic Escherichia coli modulates polymorphonuclear leukocyte function.
    Infect Immun. 2005 Sep;73(9):5301-10 PMID: 16113245
  105. Sat, the secreted autotransporter toxin of uropathogenic Escherichia coli, is a vacuolating cytotoxin for bladder and kidney epithelial cells.
    Infect Immun. 2002 Aug;70(8):4539-46 PMID: 12117966
  106. Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli.
    Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17020-4 PMID: 12471157
  107. Asymptomatic bacteriuria Escherichia coli strains: adhesins, growth and competition.
    FEMS Microbiol Lett. 2006 Sep;262(1):22-30 PMID: 16907735
  108. Regulatory Interactions among adhesin gene systems of uropathogenic Escherichia coli.
    Infect Immun. 2008 Feb;76(2):771-80 PMID: 18039830
  109. Bacterial outer membrane vesicles and the host-pathogen interaction.
    Genes Dev. 2005 Nov 15;19(22):2645-55 PMID: 16291643
  110. Histone modifications induced by a family of bacterial toxins.
    Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13467-72 PMID: 17675409
  111. Type 1 fimbriae and extracellular polysaccharides are preeminent uropathogenic Escherichia coli virulence determinants in the murine urinary tract.
    Mol Microbiol. 2002 Aug;45(4):1079-93 PMID: 12180926
  112. Role of phase variation of type 1 fimbriae in a uropathogenic Escherichia coli cystitis isolate during urinary tract infection.
    Infect Immun. 2006 Feb;74(2):1387-93 PMID: 16428790
  113. Release of the type I secreted alpha-haemolysin via outer membrane vesicles from Escherichia coli.
    Mol Microbiol. 2006 Jan;59(1):99-112 PMID: 16359321
  114. Global gene expression profiling of the asymptomatic bacteriuria Escherichia coli strain 83972 in the human urinary tract.
    Infect Immun. 2006 Jun;74(6):3565-75 PMID: 16714589
  115. The K1 capsule modulates trafficking of E. coli-containing vacuoles and enhances intracellular bacterial survival in human brain microvascular endothelial cells.
    Cell Microbiol. 2003 Apr;5(4):245-52 PMID: 12675682
Article Info
Journal
Experimental and molecular pathology
Abbr.
Exp Mol Pathol
ISSN
1096-0945
Published
2008-08-00
Epub
2008-00-08
Pages
11-9
Language
English
Region
Netherlands
NLM ID
0370711
PMCID
PMC2595135
Subset
IM
Grants
NIDDK NIH HHS · R01 DK068585 · United States
NIDDK NIH HHS · R01 DK068585-05 · United States
NIAID NIH HHS · T32 AI055434 · United States
NIDDK NIH HHS · DK068585 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com