Skip to content
1887

Abstract

Group B (GBS) causes various infections in adults, including urinary tract infection (UTI) and asymptomatic bacteriuria (ABU). Some bacteria that cause ABU can utilize urine as a substrate for growth, which can promote asymptomatic colonization in the host. An analysis of diverse GBS isolates associated with ABU and UTI for growth in human urine has not been undertaken. Here, we examined a large collection of clinical urinary GBS isolates from individuals with acute UTI (=62), and ABU with bacteriuria ≥10 c.f.u. ml (=206) or <10 c.f.u. ml (=90) for their ability to grow in human urine. Among all 358 GBS isolates analysed, 40 exhibited robust growth in urine in contrast to 25 that were unable to grow and non-culturable after incubation in urine. Growth phenotypes were disproportionately represented among the different groups of isolates, whereby robust growth was significantly more likely to be associated with high-grade ABU versus low-grade ABU or acute UTI (38/40 vs. 11/25; odds ratio 4.6, 95% CI, 1.5–14.8). Growth of bacteria in urine can depend on iron bioavailability, and we therefore performed growth assays using urine supplemented with 2,2-dipyridyl to chelate iron. In contrast to a control strain of ABU for which iron limitation significantly attenuated growth, iron sequestration had no significant attenuation effect on the growth of ABU GBS strain 834 in urine. Despite this finding, PCR confirmed the presence of several known growth-associated genes in GBS 834, including for iron uptake. We conclude that GBS adaptation for growth in human urine is more likely to be associated with high-grade ABU than acute UTI, and for GBS 834, this growth trait is not significantly constrained by conditions of iron sequestration.

Funding
This study was supported by the:
  • National Health and Medical Research Council (Award 2021475)
    • Principal Award Recipient: GlenC Ulett
  • National Health and Medical Research Council (Award 2021475)
    • Principal Award Recipient: MatthewSullivan
  • National Health and Medical Research Council (Award 2021475)
    • Principal Award Recipient: KelvinGoh
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.001533
2025-02-20
2026-04-14

Metrics

Loading full text...

Full text loading...

/deliver/fulltext/micro/171/2/mic001533.html?itemId=/content/journal/micro/10.1099/mic.0.001533&mimeType=html&fmt=ahah

References

  1. Paul P, Gonçalves BP, Le Doare K, Lawn JE. 20 million pregnant women with group B Streptococcus carriage: consequences, challenges, and opportunities for prevention. Curr Opin Pediatr 2023; 35:223–230 [View Article] [PubMed]
    [Google Scholar]
  2. Edwards MS, Baker CJ. Group B streptococcal infections in elderly adults. Clin Infect Dis 2005; 41:839–847 [View Article] [PubMed]
    [Google Scholar]
  3. Farley MM. Group B streptococcal disease in nonpregnant adults. Clin Infect Dis 2001; 33:556–561 [View Article] [PubMed]
    [Google Scholar]
  4. Goh KGK, Desai D, Thapa R, Prince D, Acharya D et al. An opportunistic pathogen under stress: how Group B Streptococcus responds to cytotoxic reactive species and conditions of metal ion imbalance to survive. FEMS Microbiol Rev 2024; 48:fuae009 [View Article] [PubMed]
    [Google Scholar]
  5. Edwards MS, Rench MA, Palazzi DL, Baker CJ. Group B streptococcal colonization and serotype-specific immunity in healthy elderly persons. Clin Infect Dis 2005; 40:352–357 [View Article]
    [Google Scholar]
  6. Jackson LA, Hilsdon R, Farley MM, Harrison LH, Reingold AL et al. Risk factors for group B streptococcal disease in adults. Ann Intern Med 1995; 123:415–420 [View Article] [PubMed]
    [Google Scholar]
  7. McKenna DS, Matson S, Northern I. Maternal group B streptococcal (GBS) genital tract colonization at term in women who have asymptomatic GBS bacteriuria. Infect Dis Obstet Gynecol 2003; 11:203–207 [View Article]
    [Google Scholar]
  8. Ulett KB, Benjamin WH Jr, Zhuo F, Xiao M, Kong F et al. Diversity of group B streptococcus serotypes causing urinary tract infection in adults. J Clin Microbiol 2009; 47:2055–2060 [View Article] [PubMed]
    [Google Scholar]
  9. Trivalle C, Martin E, Martel P, Jacque B, Menard JF et al. Group B streptococcal bacteraemia in the elderly. J Med Microbiol 1998; 47:649–652 [View Article] [PubMed]
    [Google Scholar]
  10. Shabayek S, Spellerberg B. Group B streptococcal colonization, molecular characteristics, and epidemiology. Front Microbiol 2018; 9:437 [View Article] [PubMed]
    [Google Scholar]
  11. Tan CK, Ulett KB, Steele M, Benjamin WH Jr, Ulett GC. Prognostic value of semi-quantitative bacteruria counts in the diagnosis of group B streptococcus urinary tract infection: a 4-year retrospective study in adult patients. BMC Infect Dis 2012; 12:273 [View Article] [PubMed]
    [Google Scholar]
  12. Watts RE, Totsika M, Challinor VL, Mabbett AN, Ulett GC et al. Contribution of siderophore systems to growth and urinary tract colonization of asymptomatic bacteriuria Escherichia coli. Infect Immun 2012; 80:333–344 [View Article]
    [Google Scholar]
  13. Chakupurakal R, Ahmed M, Sobithadevi DN, Chinnappan S, Reynolds T. Urinary tract pathogens and resistance pattern. J Clin Pathol 2010; 63:652–654 [View Article] [PubMed]
    [Google Scholar]
  14. Gordon DM, Riley MA. A theoretical and experimental analysis of bacterial growth in the bladder. Mol Microbiol 1992; 6:555–562 [View Article] [PubMed]
    [Google Scholar]
  15. Roos V, Ulett GC, Schembri MA, Klemm P. The asymptomatic bacteriuria Escherichia coli strain 83972 outcompetes uropathogenic E. coli strains in human urine. Infect Immun 2006; 74:615–624 [View Article]
    [Google Scholar]
  16. Stamey TA, Mihara G. Observations on the growth of urethral and vaginal bacteria in sterile urine. J Urol 1980; 124:461–463 [View Article]
    [Google Scholar]
  17. Ipe DS, Horton E, Ulett GC. The basics of bacteriuria: strategies of microbes for persistence in urine. Front Cell Infect Microbiol 2016; 6:14 [View Article] [PubMed]
    [Google Scholar]
  18. Ipe DS, Sundac L, Benjamin WH, Moore KH, Ulett GC. Asymptomatic bacteriuria: prevalence rates of causal microorganisms, etiology of infection in different patient populations, and recent advances in molecular detection. FEMS Microbiol Lett 2013; 346:1–10 [View Article] [PubMed]
    [Google Scholar]
  19. Skaar EP, Humayun M, Bae T, DeBord KL, Schneewind O. Iron-source preference of Staphylococcus aureus infections. Science 2004; 305:1626–1628 [View Article] [PubMed]
    [Google Scholar]
  20. Brown JS, Holden DW. Iron acquisition by Gram-positive bacterial pathogens. Microbes Infect 2002; 4:1149–1156 [View Article] [PubMed]
    [Google Scholar]
  21. Mabbett AN, Ulett GC, Watts RE, Tree JJ, Totsika M et al. Virulence properties of asymptomatic bacteriuria Escherichia coli. Int J Med Microbiol 2009; 299:53–63 [View Article] [PubMed]
    [Google Scholar]
  22. Ipe DS, Ben Zakour NL, Sullivan MJ, Beatson SA, Ulett KB et al. Discovery and characterization of human-urine utilization by asymptomatic-bacteriuria-causing Streptococcus agalactiae. Infect Immun 2016; 84:307–319 [View Article] [PubMed]
    [Google Scholar]
  23. Nakouti I, Hobbs G. A new approach to studying ion uptake by actinomycetes. J Basic Microbiol 2013; 53:913–916 [View Article] [PubMed]
    [Google Scholar]
  24. Nakouti I, Sihanonth P, Hobbs G. A new approach to isolating siderophore-producing actinobacteria. Lett Appl Microbiol 2012; 55:68–72 [View Article] [PubMed]
    [Google Scholar]
  25. Sitkiewicz I, Musser JM. Analysis of growth-phase regulated genes in Streptococcus agalactiae by global transcript profiling. BMC Microbiol 2009; 9:32 [View Article] [PubMed]
    [Google Scholar]
  26. Mereghetti L, Sitkiewicz I, Green NM, Musser JM. Extensive adaptive changes occur in the transcriptome of Streptococcus agalactiae (group B Streptococcus) in response to incubation with human blood. PLoS One 2008; 3:e3143 [View Article] [PubMed]
    [Google Scholar]
  27. Pearson WR, Lipman DJ. Improved tools for biological sequence comparison. Proc Natl Acad Sci USA 1988; 85:2444–2448 [View Article] [PubMed]
    [Google Scholar]
  28. Tettelin H, Masignani V, Cieslewicz MJ, Eisen JA, Peterson S et al. Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae. Proc Natl Acad Sci USA 2002; 99:12391–12396 [View Article]
    [Google Scholar]
  29. Salvador E, Wagenlehner F, Köhler C-D, Mellmann A, Hacker J et al. Comparison of asymptomatic bacteriuria Escherichia coli isolates from healthy individuals versus those from hospital patients shows that long-term bladder colonization selects for attenuated virulence phenotypes. Infect Immun 2012; 80:668–678 [View Article]
    [Google Scholar]
  30. Ipe DS, Sullivan MJ, Goh KGK, Hashimi SM, Munn AL et al. Conserved bacterial de novo guanine biosynthesis pathway enables microbial survival and colonization in the environmental niche of the urinary tract. ISME J 2021; 15:2158–2162 [View Article] [PubMed]
    [Google Scholar]
  31. Shepard BD, Gilmore MS. Differential expression of virulence-related genes in Enterococcus faecalis in response to biological cues in serum and urine. Infect Immun 2002; 70:4344–4352 [View Article]
    [Google Scholar]
  32. Vebo HC, Solheim M, Snipen L, Nes IF, Brede DA. Comparative genomic analysis of pathogenic and probiotic Enterococcus faecalis isolates, and their transcriptional responses to growth in human urine. PLoS One 2010; 5:e12489 [View Article] [PubMed]
    [Google Scholar]
  33. Bates CS, Montañez GE, Woods CR, Vincent RM, Eichenbaum Z. Identification and characterization of a Streptococcus pyogenes operon involved in binding of hemoproteins and acquisition of iron. Infect Immun 2003; 71:1042–1055 [View Article] [PubMed]
    [Google Scholar]
  34. Evans SL, Arceneaux JE, Byers BR, Martin ME, Aranha H. Ferrous iron transport in Streptococcus mutans. J Bacteriol 1986; 168:1096–1099 [View Article] [PubMed]
    [Google Scholar]
  35. Clancy A, Loar JW, Speziali CD, Oberg M, Heinrichs DE et al. Evidence for siderophore‐dependent iron acquisition in group B streptococcus. Mol Microbiol 2006; 59:707–721 [View Article]
    [Google Scholar]
  36. Yamamoto Y, Poyart C, Trieu-Cuot P, Lamberet G, Gruss A et al. Respiration metabolism of Group B Streptococcus is activated by environmental haem and quinone and contributes to virulence. Mol Microbiol 2005; 56:525–534 [View Article] [PubMed]
    [Google Scholar]
  37. Samen U, Gottschalk B, Eikmanns BJ, Reinscheid DJ. Relevance of peptide uptake systems to the physiology and virulence of Streptococcus agalactiae. J Bacteriol 2004; 186:1398–1408 [View Article] [PubMed]
    [Google Scholar]
  38. Sitkiewicz I, Green NM, Guo N, Bongiovanni AM, Witkin SS et al. Transcriptome adaptation of group B Streptococcus to growth in human amniotic fluid. PLoS One 2009; 4:e6114 [View Article] [PubMed]
    [Google Scholar]
  39. Tasevska N, Runswick SA, McTaggart A, Bingham SA. Urinary sucrose and fructose as biomarkers for sugar consumption. Cancer Epidemiol Biomarkers Prev 2005; 14:1287–1294 [View Article]
    [Google Scholar]
  40. Bouatra S, Aziat F, Mandal R, Guo AC, Wilson MR et al. The human urine metabolome. PLoS One 2013; 8:e73076 [View Article] [PubMed]
    [Google Scholar]
  41. Ipe DS, Ulett GC. Evaluation of the in vitro growth of urinary tract infection-causing Gram-negative and Gram-positive bacteria in a proposed synthetic human urine (SHU) medium. J Microbiol Methods 2016; 127:164–171 [View Article] [PubMed]
    [Google Scholar]
/content/journal/micro/10.1099/mic.0.001533
Loading
/content/journal/micro/10.1099/mic.0.001533
Loading

Data & Media loading...

Supplements

Supplementary material 1

Supplementary material 2

Supplementary material 3

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