To establish infection, enteric pathogens integrate environmental cues to navigate the gastrointestinal tract (GIT) and precisely control expression of virulence determinants. During passage through the GIT, pathogens encounter relatively high levels of oxygen in the small intestine before transit to the oxygen-limited environment of the colon. However, how bacterial pathogens sense oxygen availability and coordinate expression of virulence traits is not resolved. Here, we demonstrate that enterohemorrhagic O157:H7 (EHEC) regulates virulence via the oxygen-responsive small RNA DicF. Under oxygen-limited conditions, DicF enhances global expression of the EHEC type three secretion system, which is a key virulence factor required for host colonization, through the transcriptional activator PchA. Mechanistically, the coding sequence (CDS) base pairs with the 5' untranslated region of the mRNA to sequester the ribosome binding site (RBS) and inhibit translation. DicF disrupts -interactions by binding to the CDS, thereby unmasking the RBS and promoting PchA expression. These findings uncover a feed-forward regulatory pathway that involves distinctive mechanisms of RNA-based regulation and that provides spatiotemporal control of EHEC virulence.
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http://dx.doi.org/10.1073/pnas.1902725116 | DOI Listing |
Microbiol Spectr
January 2025
Institute of Bioinformatics and Applied Biotechnology, Bengaluru, Karnataka, India.
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View Article and Find Full Text PDFNucleic Acids Res
January 2025
School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
Genome-wide identification of binding profiles for DNA-binding proteins from the limited number of intracellular pathogens in infection studies is crucial for understanding virulence and cellular processes but remains challenging, as the current ChIP-exo is designed for high-input bacterial cells (>1010). Here, we developed an optimized ChIP-mini method, a low-input ChIP-exo utilizing a 5,000-fold reduced number of initial bacterial cells and an analysis pipeline, to identify genome-wide binding dynamics of DNA-binding proteins in host-infected pathogens. Applying ChIP-mini to intracellular Salmonella Typhimurium, we identified 642 and 1,837 binding sites of H-NS and RpoD, respectively, elucidating changes in their binding position and binding intensity during infection.
View Article and Find Full Text PDFQuorum sensing (QS) is a mechanism of intercellular communication that enables microbes to alter gene expression and adapt to the environment. This cell-cell signaling is necessary for intra- and interspecies behaviors such as virulence and biofilm formation. While QS has been extensively studied in bacteria, little is known about cell-cell communication in archaea.
View Article and Find Full Text PDFFront Chem
January 2025
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, East China University of Science and Technology, Shanghai, China.
Cyclic di-guanosine monophosphate (c-di-GMP) acts as a second messenger regulating bacterial behaviors including cell cycling, biofilm formation, adhesion, and virulence. Monitoring c-di-GMP levels is crucial for understanding these processes and designing inhibitors to combat biofilm-related antibiotic resistance. Here, we developed a genetically encoded biosensor, cdiGEBS, based on the transcriptional activity of the c-di-GMP-responsive transcription factor MrkH.
View Article and Find Full Text PDFPlant J
January 2025
Center for Legume Plant Genetics and Systems Biology, Oil Crops Research Institute, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
Bacterial wilt caused by Ralstonia solanacearum is a devastating disease affecting a great many crops including peanut. The pathogen damages plants via secreting type Ш effector proteins (T3Es) into hosts for pathogenicity. Here, we characterized RipAU was among the most toxic effectors as ΔRipAU completely lost its pathogenicity to peanuts.
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