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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2020-04-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00932-19 |
| _version_ | 1818398465311375360 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T07:05:13Z |
| format | Article |
| id | doaj.art-24ebd4fa8e2649098341dc183de237af |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-14T07:05:13Z |
| publishDate | 2020-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-24ebd4fa8e2649098341dc183de237af2022-12-21T23:12:14ZengAmerican Society for MicrobiologymSphere2379-50422020-04-015210.1128/mSphere.00932-19Host Cathelicidin Exacerbates Group B <italic toggle="yes">Streptococcus</italic> Urinary Tract InfectionKathryn A. Patras0Alison Coady1Priyanka Babu2Samuel R. Shing3Albert D. Ha4Emma Rooholfada5Stephanie L. Brandt6Matthew Geriak7Richard L. Gallo8Victor Nizet9Department of Pediatrics, University of California, San Diego, La Jolla, California, USADepartment of Pediatrics, University of California, San Diego, La Jolla, California, USADepartment of Pediatrics, University of California, San Diego, La Jolla, California, USADepartment of Pediatrics, University of California, San Diego, La Jolla, California, USADepartment of Pediatrics, University of California, San Diego, La Jolla, California, USADepartment of Pediatrics, University of California, San Diego, La Jolla, California, USADepartment of Pediatrics, University of California, San Diego, La Jolla, California, USASharp Memorial Hospital, San Diego, California, USADepartment of Dermatology, University of California, San Diego, La Jolla, California, USADepartment of Pediatrics, University of California, San Diego, La Jolla, California, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mSphere.00932-19cathelicidingroup B Streptococcusinnate immunitymast cellurinary tract infection |
| spellingShingle | 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 mSphere cathelicidin group B Streptococcus innate immunity mast cell urinary tract infection |
| title | 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_short | 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 |
| topic | cathelicidin group B Streptococcus innate immunity mast cell urinary tract infection |
| url | https://journals.asm.org/doi/10.1128/mSphere.00932-19 |
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