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Biology subjects

D'Agostino, G. D.

Publications and source records attributed to D'Agostino, G. D..

2 recordsLinked to original sources

Competing Inter-Domain Quorum-Sensing Systems Control Prophage Lysis-Lysogeny Decisions

Phaeobacter inhibens T5T harbors three LuxI/LuxR quorum-sensing systems: one encoded by the host and one in each of two prophages. Each prophage quorum-sensing autoinducer activates its own lysogeny program and that of the co-resident prophage. By driving competitors toward lysogeny, prophages deny their rivals access to susceptible hosts. One prophage engages in a bidirectional interaction with the host: the prophage activates host quorum sensing, while the host represses prophage quorum sensing. Because the host and prophage autoinducers exert opposing effects on the same prophage promoter, the prophages lysis-lysogeny decision depends on the ratio of the two autoinducers rather than their absolute concentrations. Ratiometric sensing allows the prophage to infer the relative abundances of infected and uninfected hosts and to commit to lysis only when uninfected hosts predominate. Phage quorum-sensing modules are widespread and undergo diversification and exchange. These findings reveal how prophages surveil and manipulate competitors that share chemical environments.

microbiology↗

Human gut bacteria produce TH17-modulating bile acid metabolites

The microbiota plays a pivotal role in gut immune homeostasis. Bacteria influence the development and function of host immune cells, including T helper cells expressing interleukin-17a (TH17 cells). We previously reported that the bile acid metabolite 3-oxolithocholic acid (3-oxoLCA) inhibits TH17 cell differentiation1. While it was suggested that gut-residing bacteria produce 3-oxoLCA, the identity of such bacteria was unknown. Furthermore, it was not clear whether 3-oxoLCA and other immunomodulatory bile acids are associated with gut inflammatory pathologies in humans. Using a high-throughput screen, we identified human gut bacteria and corresponding enzymes that convert the secondary bile acid lithocholic acid into 3-oxoLCA as well as the abundant gut metabolite isolithocholic acid (isoLCA). Like 3-oxoLCA, isoLCA suppressed TH17 differentiation by inhibiting ROR{gamma}t (retinoic acid receptor-related orphan nuclear receptor {gamma}t), a key TH17 cell-promoting transcription factor. Levels of both 3-oxoLCA and isoLCA and the 3-hydroxysteroid dehydrogenase (3-HSDH) genes required for their biosynthesis were significantly reduced in patients with inflammatory bowel diseases (IBD). Moreover, levels of these bile acids were inversely correlated with expression of TH17 cell-associated genes. Overall, our data suggest that bacterially produced TH17 cell-inhibitory bile acids may reduce the risk of autoimmune and inflammatory disorders such as IBD.

immunology↗