TprA/PhrA Quorum Sensing System Has a Major Effect on Pneumococcal Survival in Respiratory Tract and Blood, and Its Activity Is Controlled by CcpA and GlnR
Streptococcus pneumoniae is able to cause deadly diseases by infecting different tissues, each with distinct environmental and nutritional compositions. We hypothesize that the adaptive capabilities of the microbe is an important facet of pneumococcal survival in fluctuating host environments. Quoru...
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Frontiers Media S.A.
2019-09-01
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Series: | Frontiers in Cellular and Infection Microbiology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2019.00326/full |
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author | Anfal Shakir Motib Anfal Shakir Motib Firas A. Y. Al-Bayati Firas A. Y. Al-Bayati Irfan Manzoor Sulman Shafeeq Anagha Kadam Oscar P. Kuipers N. Luisa Hiller Peter W. Andrew Hasan Yesilkaya |
author_facet | Anfal Shakir Motib Anfal Shakir Motib Firas A. Y. Al-Bayati Firas A. Y. Al-Bayati Irfan Manzoor Sulman Shafeeq Anagha Kadam Oscar P. Kuipers N. Luisa Hiller Peter W. Andrew Hasan Yesilkaya |
author_sort | Anfal Shakir Motib |
collection | DOAJ |
description | Streptococcus pneumoniae is able to cause deadly diseases by infecting different tissues, each with distinct environmental and nutritional compositions. We hypothesize that the adaptive capabilities of the microbe is an important facet of pneumococcal survival in fluctuating host environments. Quorum-sensing (QS) mechanisms are pivotal for microbial host adaptation. We previously demonstrated that the TprA/PhrA QS system is required for pneumococcal utilization of galactose and mannose, neuraminidase activity, and virulence. We also showed that the system can be modulated by using linear molecularly imprinted polymers. Due to being a drugable target, we further studied the operation of this QS system in S. pneumoniae. We found that TprA controls the expression of nine different operons on galactose and mannose. Our data revealed that TprA expression is modulated by a complex regulatory network, where the master regulators CcpA and GlnR are involved in a sugar dependent manner. Mutants in the TprA/PhrA system are highly attenuated in their survival in nasopharynx and lungs after intranasal infection, and growth in blood after intravenous infection. |
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issn | 2235-2988 |
language | English |
last_indexed | 2024-12-14T00:17:11Z |
publishDate | 2019-09-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Cellular and Infection Microbiology |
spelling | doaj.art-f6e4f5c35c8c475a897ddf7ceb29324b2022-12-21T23:25:27ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882019-09-01910.3389/fcimb.2019.00326472435TprA/PhrA Quorum Sensing System Has a Major Effect on Pneumococcal Survival in Respiratory Tract and Blood, and Its Activity Is Controlled by CcpA and GlnRAnfal Shakir Motib0Anfal Shakir Motib1Firas A. Y. Al-Bayati2Firas A. Y. Al-Bayati3Irfan Manzoor4Sulman Shafeeq5Anagha Kadam6Oscar P. Kuipers7N. Luisa Hiller8Peter W. Andrew9Hasan Yesilkaya10Department of Infection, Immunity & Inflammation, University of Leicester, Leicester, United KingdomDepartment of Microbiology, College of Medicine, University of Diyala, Baqubah, IraqDepartment of Infection, Immunity & Inflammation, University of Leicester, Leicester, United KingdomCollege of Pharmacy, University of Kirkuk, Kirkuk, IraqMolecular Genetics, University of Groningen, Groningen, NetherlandsMolecular Genetics, University of Groningen, Groningen, NetherlandsDepartment of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United StatesMolecular Genetics, University of Groningen, Groningen, NetherlandsDepartment of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United StatesDepartment of Infection, Immunity & Inflammation, University of Leicester, Leicester, United KingdomDepartment of Infection, Immunity & Inflammation, University of Leicester, Leicester, United KingdomStreptococcus pneumoniae is able to cause deadly diseases by infecting different tissues, each with distinct environmental and nutritional compositions. We hypothesize that the adaptive capabilities of the microbe is an important facet of pneumococcal survival in fluctuating host environments. Quorum-sensing (QS) mechanisms are pivotal for microbial host adaptation. We previously demonstrated that the TprA/PhrA QS system is required for pneumococcal utilization of galactose and mannose, neuraminidase activity, and virulence. We also showed that the system can be modulated by using linear molecularly imprinted polymers. Due to being a drugable target, we further studied the operation of this QS system in S. pneumoniae. We found that TprA controls the expression of nine different operons on galactose and mannose. Our data revealed that TprA expression is modulated by a complex regulatory network, where the master regulators CcpA and GlnR are involved in a sugar dependent manner. Mutants in the TprA/PhrA system are highly attenuated in their survival in nasopharynx and lungs after intranasal infection, and growth in blood after intravenous infection.https://www.frontiersin.org/article/10.3389/fcimb.2019.00326/fullStreptococcus pneumoniaetranscriptional regulationTprA/PhrAsugar metabolismvirulence |
spellingShingle | Anfal Shakir Motib Anfal Shakir Motib Firas A. Y. Al-Bayati Firas A. Y. Al-Bayati Irfan Manzoor Sulman Shafeeq Anagha Kadam Oscar P. Kuipers N. Luisa Hiller Peter W. Andrew Hasan Yesilkaya TprA/PhrA Quorum Sensing System Has a Major Effect on Pneumococcal Survival in Respiratory Tract and Blood, and Its Activity Is Controlled by CcpA and GlnR Frontiers in Cellular and Infection Microbiology Streptococcus pneumoniae transcriptional regulation TprA/PhrA sugar metabolism virulence |
title | TprA/PhrA Quorum Sensing System Has a Major Effect on Pneumococcal Survival in Respiratory Tract and Blood, and Its Activity Is Controlled by CcpA and GlnR |
title_full | TprA/PhrA Quorum Sensing System Has a Major Effect on Pneumococcal Survival in Respiratory Tract and Blood, and Its Activity Is Controlled by CcpA and GlnR |
title_fullStr | TprA/PhrA Quorum Sensing System Has a Major Effect on Pneumococcal Survival in Respiratory Tract and Blood, and Its Activity Is Controlled by CcpA and GlnR |
title_full_unstemmed | TprA/PhrA Quorum Sensing System Has a Major Effect on Pneumococcal Survival in Respiratory Tract and Blood, and Its Activity Is Controlled by CcpA and GlnR |
title_short | TprA/PhrA Quorum Sensing System Has a Major Effect on Pneumococcal Survival in Respiratory Tract and Blood, and Its Activity Is Controlled by CcpA and GlnR |
title_sort | tpra phra quorum sensing system has a major effect on pneumococcal survival in respiratory tract and blood and its activity is controlled by ccpa and glnr |
topic | Streptococcus pneumoniae transcriptional regulation TprA/PhrA sugar metabolism virulence |
url | https://www.frontiersin.org/article/10.3389/fcimb.2019.00326/full |
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