PRD-Containing Virulence Regulators (PCVRs) in Pathogenic Bacteria
Bacterial pathogens rely on a complex network of regulatory proteins to adapt to hostile and nutrient-limiting host environments. The phosphoenolpyruvate phosphotransferase system (PTS) is a conserved pathway in bacteria that couples transport of sugars with phosphorylation to monitor host carbohydr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2021.772874/full |
| _version_ | 1818727769747488768 |
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| author | Joseph S. Rom Meaghan T. Hart Kevin S. McIver Kevin S. McIver |
| author_facet | Joseph S. Rom Meaghan T. Hart Kevin S. McIver Kevin S. McIver |
| author_sort | Joseph S. Rom |
| collection | DOAJ |
| description | Bacterial pathogens rely on a complex network of regulatory proteins to adapt to hostile and nutrient-limiting host environments. The phosphoenolpyruvate phosphotransferase system (PTS) is a conserved pathway in bacteria that couples transport of sugars with phosphorylation to monitor host carbohydrate availability. A family of structurally homologous PTS-regulatory-domain-containing virulence regulators (PCVRs) has been recognized in divergent bacterial pathogens, including Streptococcus pyogenes Mga and Bacillus anthracis AtxA. These paradigm PCVRs undergo phosphorylation, potentially via the PTS, which impacts their dimerization and their activity. Recent work with predicted PCVRs from Streptococcus pneumoniae (MgaSpn) and Enterococcus faecalis (MafR) suggest they interact with DNA like nucleoid-associating proteins. Yet, Mga binds to promoter sequences as a homo-dimeric transcription factor, suggesting a bi-modal interaction with DNA. High-resolution crystal structures of 3 PCVRs have validated the domain structure, but also raised additional questions such as how ubiquitous are PCVRs, is PTS-mediated histidine phosphorylation via potential PCVRs widespread, do specific sugars signal through PCVRs, and do PCVRs interact with DNA both as transcription factors and nucleoid-associating proteins? Here, we will review known and putative PCVRs based on key domain and functional characteristics and consider their roles as both transcription factors and possibly chromatin-structuring proteins. |
| first_indexed | 2024-12-17T22:19:22Z |
| format | Article |
| id | doaj.art-a705a9a6b8534580b65ca72bfd042668 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-17T22:19:22Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-a705a9a6b8534580b65ca72bfd0426682022-12-21T21:30:30ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-10-011110.3389/fcimb.2021.772874772874PRD-Containing Virulence Regulators (PCVRs) in Pathogenic BacteriaJoseph S. Rom0Meaghan T. Hart1Kevin S. McIver2Kevin S. McIver3Cell Biology & Molecular Genetics, University of Maryland, College Park, MD, United StatesCell Biology & Molecular Genetics, University of Maryland, College Park, MD, United StatesCell Biology & Molecular Genetics, University of Maryland, College Park, MD, United StatesMaryland Pathogen Research Institute, University of Maryland, College Park, MD, United StatesBacterial pathogens rely on a complex network of regulatory proteins to adapt to hostile and nutrient-limiting host environments. The phosphoenolpyruvate phosphotransferase system (PTS) is a conserved pathway in bacteria that couples transport of sugars with phosphorylation to monitor host carbohydrate availability. A family of structurally homologous PTS-regulatory-domain-containing virulence regulators (PCVRs) has been recognized in divergent bacterial pathogens, including Streptococcus pyogenes Mga and Bacillus anthracis AtxA. These paradigm PCVRs undergo phosphorylation, potentially via the PTS, which impacts their dimerization and their activity. Recent work with predicted PCVRs from Streptococcus pneumoniae (MgaSpn) and Enterococcus faecalis (MafR) suggest they interact with DNA like nucleoid-associating proteins. Yet, Mga binds to promoter sequences as a homo-dimeric transcription factor, suggesting a bi-modal interaction with DNA. High-resolution crystal structures of 3 PCVRs have validated the domain structure, but also raised additional questions such as how ubiquitous are PCVRs, is PTS-mediated histidine phosphorylation via potential PCVRs widespread, do specific sugars signal through PCVRs, and do PCVRs interact with DNA both as transcription factors and nucleoid-associating proteins? Here, we will review known and putative PCVRs based on key domain and functional characteristics and consider their roles as both transcription factors and possibly chromatin-structuring proteins.https://www.frontiersin.org/articles/10.3389/fcimb.2021.772874/fullPCVRPTS phosphorylationAtxAMgaMgaSpnMafR |
| spellingShingle | Joseph S. Rom Meaghan T. Hart Kevin S. McIver Kevin S. McIver PRD-Containing Virulence Regulators (PCVRs) in Pathogenic Bacteria Frontiers in Cellular and Infection Microbiology PCVR PTS phosphorylation AtxA Mga MgaSpn MafR |
| title | PRD-Containing Virulence Regulators (PCVRs) in Pathogenic Bacteria |
| title_full | PRD-Containing Virulence Regulators (PCVRs) in Pathogenic Bacteria |
| title_fullStr | PRD-Containing Virulence Regulators (PCVRs) in Pathogenic Bacteria |
| title_full_unstemmed | PRD-Containing Virulence Regulators (PCVRs) in Pathogenic Bacteria |
| title_short | PRD-Containing Virulence Regulators (PCVRs) in Pathogenic Bacteria |
| title_sort | prd containing virulence regulators pcvrs in pathogenic bacteria |
| topic | PCVR PTS phosphorylation AtxA Mga MgaSpn MafR |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2021.772874/full |
| work_keys_str_mv | AT josephsrom prdcontainingvirulenceregulatorspcvrsinpathogenicbacteria AT meaghanthart prdcontainingvirulenceregulatorspcvrsinpathogenicbacteria AT kevinsmciver prdcontainingvirulenceregulatorspcvrsinpathogenicbacteria AT kevinsmciver prdcontainingvirulenceregulatorspcvrsinpathogenicbacteria |