Host Cathelicidin Exacerbates Group B <italic toggle="yes">Streptococcus</italic> Urinary Tract Infection

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. H...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	cathelicidin group B Streptococcus innate immunity mast cell urinary tract infection Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/24ebd4fa8e2649098341dc183de237af
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:24ebd4fa8e2649098341dc183de237af
record_format	dspace
spelling	oai:doaj.org-article:24ebd4fa8e2649098341dc183de237af2021-11-15T15:29:16ZHost Cathelicidin Exacerbates Group B <italic toggle="yes">Streptococcus</italic> Urinary Tract Infection10.1128/mSphere.00932-192379-5042https://doaj.org/article/24ebd4fa8e2649098341dc183de237af2020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00932-19https://doaj.org/toc/2379-5042ABSTRACT 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. IMPORTANCE Certain populations such as diabetic individuals are at increased risk for developing urinary tract infections (UTI), although the underlying reasons for this susceptibility are not fully known. Additionally, diabetics are more likely to become infected with certain types of bacteria, such as group B Streptococcus (GBS). In this study, we find that an antimicrobial peptide called cathelicidin, which is thought to protect the bladder from infection, is ineffective in controlling GBS and alters the type of immune cells that migrate to the bladder during infection. Using a mouse model of diabetes, we observe that diabetic mice are more susceptible to GBS infection even though they also have more infiltrating immune cells and increased production of cathelicidin. Taken together, our findings identify this antimicrobial peptide as a potential contributor to increased susceptibility of diabetic individuals to GBS UTI.Kathryn A. PatrasAlison CoadyPriyanka BabuSamuel R. ShingAlbert D. HaEmma RooholfadaStephanie L. BrandtMatthew GeriakRichard L. GalloVictor NizetAmerican Society for Microbiologyarticlecathelicidingroup B Streptococcusinnate immunitymast cellurinary tract infectionMicrobiologyQR1-502ENmSphere, Vol 5, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	cathelicidin group B Streptococcus innate immunity mast cell urinary tract infection Microbiology QR1-502
spellingShingle	cathelicidin group B Streptococcus innate immunity mast cell urinary tract infection Microbiology QR1-502 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 Host Cathelicidin Exacerbates Group B <italic toggle="yes">Streptococcus</italic> Urinary Tract Infection
description	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. IMPORTANCE Certain populations such as diabetic individuals are at increased risk for developing urinary tract infections (UTI), although the underlying reasons for this susceptibility are not fully known. Additionally, diabetics are more likely to become infected with certain types of bacteria, such as group B Streptococcus (GBS). In this study, we find that an antimicrobial peptide called cathelicidin, which is thought to protect the bladder from infection, is ineffective in controlling GBS and alters the type of immune cells that migrate to the bladder during infection. Using a mouse model of diabetes, we observe that diabetic mice are more susceptible to GBS infection even though they also have more infiltrating immune cells and increased production of cathelicidin. Taken together, our findings identify this antimicrobial peptide as a potential contributor to increased susceptibility of diabetic individuals to GBS UTI.
format	article
author	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
author_facet	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
author_sort	Kathryn A. Patras
title	Host Cathelicidin Exacerbates Group B <italic toggle="yes">Streptococcus</italic> Urinary Tract Infection
title_short	Host Cathelicidin Exacerbates Group B <italic toggle="yes">Streptococcus</italic> Urinary Tract Infection
title_full	Host Cathelicidin Exacerbates Group B <italic toggle="yes">Streptococcus</italic> Urinary Tract Infection
title_fullStr	Host Cathelicidin Exacerbates Group B <italic toggle="yes">Streptococcus</italic> Urinary Tract Infection
title_full_unstemmed	Host Cathelicidin Exacerbates Group B <italic toggle="yes">Streptococcus</italic> Urinary Tract Infection
title_sort	host cathelicidin exacerbates group b <italic toggle="yes">streptococcus</italic> urinary tract infection
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/24ebd4fa8e2649098341dc183de237af
work_keys_str_mv	AT kathrynapatras hostcathelicidinexacerbatesgroupbitalictoggleyesstreptococcusitalicurinarytractinfection AT alisoncoady hostcathelicidinexacerbatesgroupbitalictoggleyesstreptococcusitalicurinarytractinfection AT priyankababu hostcathelicidinexacerbatesgroupbitalictoggleyesstreptococcusitalicurinarytractinfection AT samuelrshing hostcathelicidinexacerbatesgroupbitalictoggleyesstreptococcusitalicurinarytractinfection AT albertdha hostcathelicidinexacerbatesgroupbitalictoggleyesstreptococcusitalicurinarytractinfection AT emmarooholfada hostcathelicidinexacerbatesgroupbitalictoggleyesstreptococcusitalicurinarytractinfection AT stephanielbrandt hostcathelicidinexacerbatesgroupbitalictoggleyesstreptococcusitalicurinarytractinfection AT matthewgeriak hostcathelicidinexacerbatesgroupbitalictoggleyesstreptococcusitalicurinarytractinfection AT richardlgallo hostcathelicidinexacerbatesgroupbitalictoggleyesstreptococcusitalicurinarytractinfection AT victornizet hostcathelicidinexacerbatesgroupbitalictoggleyesstreptococcusitalicurinarytractinfection
_version_	1718427873240416256

Host Cathelicidin Exacerbates Group B <italic toggle="yes">Streptococcus</italic> Urinary Tract Infection

Ejemplares similares