Lipoprotein Lpp and L, D-transpeptidases regulate the master regulator of virulence AggR in EAEC
Abstract Enteroaggregative Escherichia coli (EAEC) is a diarrheagenic pathotype associated with traveler’s diarrhea, foodborne outbreaks, and sporadic diarrhea in industrialized and developing countries. Regulation of virulence factors in EAEC is mediated by the master regulator AggR, an AraC/XylS f...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-96373-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850172468542570496 |
|---|---|
| author | Diana Rodriguez-Valverde Nancy Leon-Montes Laura Belmont-Monroy Fernando Ruiz-Perez Araceli E. Santiago |
| author_facet | Diana Rodriguez-Valverde Nancy Leon-Montes Laura Belmont-Monroy Fernando Ruiz-Perez Araceli E. Santiago |
| author_sort | Diana Rodriguez-Valverde |
| collection | DOAJ |
| description | Abstract Enteroaggregative Escherichia coli (EAEC) is a diarrheagenic pathotype associated with traveler’s diarrhea, foodborne outbreaks, and sporadic diarrhea in industrialized and developing countries. Regulation of virulence factors in EAEC is mediated by the master regulator AggR, an AraC/XylS family member controlling the expression of more than 44 genes associated with metabolism and virulence. Although the AggR regulon is well-characterized, the mechanism and upstream signaling cascades that regulate its activation are poorly understood. This study demonstrates that Lpp (Braun’s lipoprotein) and L, D-transpeptidases are required for AggR activation. We found that deletion lpp in EAEC resulted in the downregulation of more than 100 genes involved in transport, metabolism, and virulence. Among the genes, fourteen transcriptional factors, including AggR, were differentially expressed in 042Δlpp. Our findings also showed that Lpp anchoring to the peptidoglycan is a requisite for AggR-activation. Hence, chemical inhibition or genetic deletion of L, D-transpeptidases encoding genes involved in the crosslink of Lpp to the peptidoglycan abolished AggR activation. Moreover, the 042Δlpp mutant exhibited reduced biofilm formation on abiotic surfaces and reduced colonization of human intestinal colonoids. This is the first study to demonstrate the tight regulation of the AraC/XylS transcriptional regulator AggR, essential in EAEC virulence and intestinal colonization by components of the bacterial cell envelope. |
| format | Article |
| id | doaj-art-62715ec4b5334b8298458a8792e2b179 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-62715ec4b5334b8298458a8792e2b1792025-08-20T02:20:05ZengNature PortfolioScientific Reports2045-23222025-04-0115111210.1038/s41598-025-96373-0Lipoprotein Lpp and L, D-transpeptidases regulate the master regulator of virulence AggR in EAECDiana Rodriguez-Valverde0Nancy Leon-Montes1Laura Belmont-Monroy2Fernando Ruiz-Perez3Araceli E. Santiago4University of Virginia, School of Medicine, Department of Pediatrics, Child Health Research CenterUniversity of Virginia, School of Medicine, Department of Pediatrics, Child Health Research CenterLaboratorio de Microbiología Molecular, Instituto Nacional de PediatríaUniversity of Virginia, School of Medicine, Department of Pediatrics, Child Health Research CenterUniversity of Virginia, School of Medicine, Department of Pediatrics, Child Health Research CenterAbstract Enteroaggregative Escherichia coli (EAEC) is a diarrheagenic pathotype associated with traveler’s diarrhea, foodborne outbreaks, and sporadic diarrhea in industrialized and developing countries. Regulation of virulence factors in EAEC is mediated by the master regulator AggR, an AraC/XylS family member controlling the expression of more than 44 genes associated with metabolism and virulence. Although the AggR regulon is well-characterized, the mechanism and upstream signaling cascades that regulate its activation are poorly understood. This study demonstrates that Lpp (Braun’s lipoprotein) and L, D-transpeptidases are required for AggR activation. We found that deletion lpp in EAEC resulted in the downregulation of more than 100 genes involved in transport, metabolism, and virulence. Among the genes, fourteen transcriptional factors, including AggR, were differentially expressed in 042Δlpp. Our findings also showed that Lpp anchoring to the peptidoglycan is a requisite for AggR-activation. Hence, chemical inhibition or genetic deletion of L, D-transpeptidases encoding genes involved in the crosslink of Lpp to the peptidoglycan abolished AggR activation. Moreover, the 042Δlpp mutant exhibited reduced biofilm formation on abiotic surfaces and reduced colonization of human intestinal colonoids. This is the first study to demonstrate the tight regulation of the AraC/XylS transcriptional regulator AggR, essential in EAEC virulence and intestinal colonization by components of the bacterial cell envelope.https://doi.org/10.1038/s41598-025-96373-0 |
| spellingShingle | Diana Rodriguez-Valverde Nancy Leon-Montes Laura Belmont-Monroy Fernando Ruiz-Perez Araceli E. Santiago Lipoprotein Lpp and L, D-transpeptidases regulate the master regulator of virulence AggR in EAEC Scientific Reports |
| title | Lipoprotein Lpp and L, D-transpeptidases regulate the master regulator of virulence AggR in EAEC |
| title_full | Lipoprotein Lpp and L, D-transpeptidases regulate the master regulator of virulence AggR in EAEC |
| title_fullStr | Lipoprotein Lpp and L, D-transpeptidases regulate the master regulator of virulence AggR in EAEC |
| title_full_unstemmed | Lipoprotein Lpp and L, D-transpeptidases regulate the master regulator of virulence AggR in EAEC |
| title_short | Lipoprotein Lpp and L, D-transpeptidases regulate the master regulator of virulence AggR in EAEC |
| title_sort | lipoprotein lpp and l d transpeptidases regulate the master regulator of virulence aggr in eaec |
| url | https://doi.org/10.1038/s41598-025-96373-0 |
| work_keys_str_mv | AT dianarodriguezvalverde lipoproteinlppandldtranspeptidasesregulatethemasterregulatorofvirulenceaggrineaec AT nancyleonmontes lipoproteinlppandldtranspeptidasesregulatethemasterregulatorofvirulenceaggrineaec AT laurabelmontmonroy lipoproteinlppandldtranspeptidasesregulatethemasterregulatorofvirulenceaggrineaec AT fernandoruizperez lipoproteinlppandldtranspeptidasesregulatethemasterregulatorofvirulenceaggrineaec AT araceliesantiago lipoproteinlppandldtranspeptidasesregulatethemasterregulatorofvirulenceaggrineaec |