Host cathelicidin exacerbates group B Streptococcus urinary tract infection

Kathryn A. Patras, Alison Coady, Priyanka Babu, Samuel R. Shing, Albert D. Ha, Emma Rooholfada, Stephanie L. Brandt, Matthew Geriak, Richard L. Gallo, Victor Nizet

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Group B Streptococcus (GBS) causes frequent urinary tract infection (UTI) in susceptible populations, including individuals with type 2 diabetes and pregnant women; however, specific host factors responsible for increased GBS susceptibility in these populations are not well characterized. Here, we investigate cathelicidin, a cationic antimicrobial peptide, known to be critical for defense during UTI with uropathogenic Escherichia coli (UPEC). We observed a loss of antimicrobial activity of human and mouse cathelicidins against GBS and UPEC in synthetic urine and no evidence for increased cathelicidin resistance in GBS urinary isolates. Furthermore, we found that GBS degrades cathelicidin in a protease-dependent manner. Surprisingly, in a UTI model, cathelicidin-deficient (Camp-/-) mice showed decreased GBS burdens and mast cell recruitment in the bladder compared to levels in wild-type (WT) mice. Pharmacologic inhibition of mast cells reduced GBS burdens and histamine release in WT but not Camp-/- mice. Streptozotocin-induced diabetic mice had increased bladder cathelicidin production and mast cell recruitment at 24 h postinfection with GBS compared to levels in nondiabetic controls. We propose that cathelicidin is an important immune regulator but ineffective antimicrobial peptide against GBS in urine. Combined, our findings may in part explain the increased frequency of GBS UTI in diabetic and pregnant individuals.

Original languageEnglish (US)
Article numbere00932-19
JournalmSphere
Volume5
Issue number2
DOIs
StatePublished - Mar 1 2020
Externally publishedYes

Keywords

  • Cathelicidin
  • Group B Streptococcus
  • Innate immunity
  • Mast cell
  • Urinary tract infection

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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