Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease [Bacterial Infections]
Deng, L., Mu, R., Weston, T. A., Spencer, B. L., Liles, R. P., Doran, K. S.
The American Society for Microbiology (ASM)
Published 2018
The American Society for Microbiology (ASM)
Published 2018
| Publication Date: |
2018-06-22
|
|---|---|
| Publisher: |
The American Society for Microbiology (ASM)
|
| Print ISSN: |
0019-9567
|
| Electronic ISSN: |
1098-5522
|
| Topics: |
Medicine
|
| Published by: |
| _version_ | 1836398981581635584 |
|---|---|
| autor | Deng, L., Mu, R., Weston, T. A., Spencer, B. L., Liles, R. P., Doran, K. S. |
| beschreibung | Streptococcus agalactiae (group B Streptococcus [GBS]) is often a commensal bacterium that colonizes healthy adults asymptomatically and is a frequent inhabitant of the vaginal tract in women. However, in immunocompromised individuals, particularly the newborn, GBS may transition to an invasive pathogen and cause serious disease. Despite the use of the currently recommended intrapartum antibiotic prophylaxis for GBS-positive mothers, GBS remains a leading cause of neonatal septicemia and meningitis. To adapt to the various host environments encountered during its disease cycle, GBS possesses multiple two-component regulatory systems (TCSs). Here we investigated the contribution of a transcriptional regulator containing a LytTR domain, LtdR, to GBS pathogenesis. Disruption of the ltdR gene in the GBS chromosome resulted in a significant increase in bacterial invasion into human cerebral microvascular endothelial cells (hCMEC) in vitro as well as the greater penetration of the blood-brain barrier (BBB) and the development of meningitis in vivo . Correspondingly, infection of hCMEC with the ltdR mutant resulted in increased secretion of the proinflammatory cytokines interleukin-8 (IL-8), CXCL-1, and IL-6. Further, using a mouse model of GBS vaginal colonization, we observed that the ltdR mutant was cleared more readily from the vaginal tract and also that infection with the ltdR mutant resulted in increased cytokine production from human vaginal epithelial cells. RNA sequencing revealed global transcriptional differences between the ltdR mutant and the parental wild-type GBS strain. These results suggest that LtdR regulates many bacterial processes that can influence GBS-host interactions to promote both bacterial persistence and disease progression. |
| citation_standardnr | 6289880 |
| datenlieferant | ipn_articles |
| feed_id | 519 |
| feed_publisher | The American Society for Microbiology (ASM) |
| feed_publisher_url | http://www.asm.org/ |
| insertion_date | 2018-06-22 |
| journaleissn | 1098-5522 |
| journalissn | 0019-9567 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Society for Microbiology (ASM) |
| quelle | Infection and Immunity |
| relation | http://iai.asm.org/cgi/content/short/86/7/e00822-17?rss=1 |
| search_space | articles |
| shingle_author_1 | Deng, L., Mu, R., Weston, T. A., Spencer, B. L., Liles, R. P., Doran, K. S. |
| shingle_author_2 | Deng, L., Mu, R., Weston, T. A., Spencer, B. L., Liles, R. P., Doran, K. S. |
| shingle_author_3 | Deng, L., Mu, R., Weston, T. A., Spencer, B. L., Liles, R. P., Doran, K. S. |
| shingle_author_4 | Deng, L., Mu, R., Weston, T. A., Spencer, B. L., Liles, R. P., Doran, K. S. |
| shingle_catch_all_1 | Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease [Bacterial Infections] Streptococcus agalactiae (group B Streptococcus [GBS]) is often a commensal bacterium that colonizes healthy adults asymptomatically and is a frequent inhabitant of the vaginal tract in women. However, in immunocompromised individuals, particularly the newborn, GBS may transition to an invasive pathogen and cause serious disease. Despite the use of the currently recommended intrapartum antibiotic prophylaxis for GBS-positive mothers, GBS remains a leading cause of neonatal septicemia and meningitis. To adapt to the various host environments encountered during its disease cycle, GBS possesses multiple two-component regulatory systems (TCSs). Here we investigated the contribution of a transcriptional regulator containing a LytTR domain, LtdR, to GBS pathogenesis. Disruption of the ltdR gene in the GBS chromosome resulted in a significant increase in bacterial invasion into human cerebral microvascular endothelial cells (hCMEC) in vitro as well as the greater penetration of the blood-brain barrier (BBB) and the development of meningitis in vivo . Correspondingly, infection of hCMEC with the ltdR mutant resulted in increased secretion of the proinflammatory cytokines interleukin-8 (IL-8), CXCL-1, and IL-6. Further, using a mouse model of GBS vaginal colonization, we observed that the ltdR mutant was cleared more readily from the vaginal tract and also that infection with the ltdR mutant resulted in increased cytokine production from human vaginal epithelial cells. RNA sequencing revealed global transcriptional differences between the ltdR mutant and the parental wild-type GBS strain. These results suggest that LtdR regulates many bacterial processes that can influence GBS-host interactions to promote both bacterial persistence and disease progression. Deng, L., Mu, R., Weston, T. A., Spencer, B. L., Liles, R. P., Doran, K. S. The American Society for Microbiology (ASM) 0019-9567 00199567 1098-5522 10985522 |
| shingle_catch_all_2 | Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease [Bacterial Infections] Streptococcus agalactiae (group B Streptococcus [GBS]) is often a commensal bacterium that colonizes healthy adults asymptomatically and is a frequent inhabitant of the vaginal tract in women. However, in immunocompromised individuals, particularly the newborn, GBS may transition to an invasive pathogen and cause serious disease. Despite the use of the currently recommended intrapartum antibiotic prophylaxis for GBS-positive mothers, GBS remains a leading cause of neonatal septicemia and meningitis. To adapt to the various host environments encountered during its disease cycle, GBS possesses multiple two-component regulatory systems (TCSs). Here we investigated the contribution of a transcriptional regulator containing a LytTR domain, LtdR, to GBS pathogenesis. Disruption of the ltdR gene in the GBS chromosome resulted in a significant increase in bacterial invasion into human cerebral microvascular endothelial cells (hCMEC) in vitro as well as the greater penetration of the blood-brain barrier (BBB) and the development of meningitis in vivo . Correspondingly, infection of hCMEC with the ltdR mutant resulted in increased secretion of the proinflammatory cytokines interleukin-8 (IL-8), CXCL-1, and IL-6. Further, using a mouse model of GBS vaginal colonization, we observed that the ltdR mutant was cleared more readily from the vaginal tract and also that infection with the ltdR mutant resulted in increased cytokine production from human vaginal epithelial cells. RNA sequencing revealed global transcriptional differences between the ltdR mutant and the parental wild-type GBS strain. These results suggest that LtdR regulates many bacterial processes that can influence GBS-host interactions to promote both bacterial persistence and disease progression. Deng, L., Mu, R., Weston, T. A., Spencer, B. L., Liles, R. P., Doran, K. S. The American Society for Microbiology (ASM) 0019-9567 00199567 1098-5522 10985522 |
| shingle_catch_all_3 | Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease [Bacterial Infections] Streptococcus agalactiae (group B Streptococcus [GBS]) is often a commensal bacterium that colonizes healthy adults asymptomatically and is a frequent inhabitant of the vaginal tract in women. However, in immunocompromised individuals, particularly the newborn, GBS may transition to an invasive pathogen and cause serious disease. Despite the use of the currently recommended intrapartum antibiotic prophylaxis for GBS-positive mothers, GBS remains a leading cause of neonatal septicemia and meningitis. To adapt to the various host environments encountered during its disease cycle, GBS possesses multiple two-component regulatory systems (TCSs). Here we investigated the contribution of a transcriptional regulator containing a LytTR domain, LtdR, to GBS pathogenesis. Disruption of the ltdR gene in the GBS chromosome resulted in a significant increase in bacterial invasion into human cerebral microvascular endothelial cells (hCMEC) in vitro as well as the greater penetration of the blood-brain barrier (BBB) and the development of meningitis in vivo . Correspondingly, infection of hCMEC with the ltdR mutant resulted in increased secretion of the proinflammatory cytokines interleukin-8 (IL-8), CXCL-1, and IL-6. Further, using a mouse model of GBS vaginal colonization, we observed that the ltdR mutant was cleared more readily from the vaginal tract and also that infection with the ltdR mutant resulted in increased cytokine production from human vaginal epithelial cells. RNA sequencing revealed global transcriptional differences between the ltdR mutant and the parental wild-type GBS strain. These results suggest that LtdR regulates many bacterial processes that can influence GBS-host interactions to promote both bacterial persistence and disease progression. Deng, L., Mu, R., Weston, T. A., Spencer, B. L., Liles, R. P., Doran, K. S. The American Society for Microbiology (ASM) 0019-9567 00199567 1098-5522 10985522 |
| shingle_catch_all_4 | Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease [Bacterial Infections] Streptococcus agalactiae (group B Streptococcus [GBS]) is often a commensal bacterium that colonizes healthy adults asymptomatically and is a frequent inhabitant of the vaginal tract in women. However, in immunocompromised individuals, particularly the newborn, GBS may transition to an invasive pathogen and cause serious disease. Despite the use of the currently recommended intrapartum antibiotic prophylaxis for GBS-positive mothers, GBS remains a leading cause of neonatal septicemia and meningitis. To adapt to the various host environments encountered during its disease cycle, GBS possesses multiple two-component regulatory systems (TCSs). Here we investigated the contribution of a transcriptional regulator containing a LytTR domain, LtdR, to GBS pathogenesis. Disruption of the ltdR gene in the GBS chromosome resulted in a significant increase in bacterial invasion into human cerebral microvascular endothelial cells (hCMEC) in vitro as well as the greater penetration of the blood-brain barrier (BBB) and the development of meningitis in vivo . Correspondingly, infection of hCMEC with the ltdR mutant resulted in increased secretion of the proinflammatory cytokines interleukin-8 (IL-8), CXCL-1, and IL-6. Further, using a mouse model of GBS vaginal colonization, we observed that the ltdR mutant was cleared more readily from the vaginal tract and also that infection with the ltdR mutant resulted in increased cytokine production from human vaginal epithelial cells. RNA sequencing revealed global transcriptional differences between the ltdR mutant and the parental wild-type GBS strain. These results suggest that LtdR regulates many bacterial processes that can influence GBS-host interactions to promote both bacterial persistence and disease progression. Deng, L., Mu, R., Weston, T. A., Spencer, B. L., Liles, R. P., Doran, K. S. The American Society for Microbiology (ASM) 0019-9567 00199567 1098-5522 10985522 |
| shingle_title_1 | Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease [Bacterial Infections] |
| shingle_title_2 | Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease [Bacterial Infections] |
| shingle_title_3 | Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease [Bacterial Infections] |
| shingle_title_4 | Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease [Bacterial Infections] |
| timestamp | 2025-06-30T23:35:42.902Z |
| titel | Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease [Bacterial Infections] |
| titel_suche | Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease [Bacterial Infections] |
| topic | WW-YZ |
| uid | ipn_articles_6289880 |