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Vitamin A and its derivative retinol are essential for the development of intestinal adaptive immunity. Retinoic acid (RA)–producing myeloid cells are central to this process, but how myeloid cells acquire retinol for conversion to RA is unknown. Here, we show that serum amyloid A (SAA) proteins—retinol-binding proteins induced in intestinal epithelial cells by the microbiota—deliver retinol to myeloid cells. We identify low-density lipoprotein (LDL) receptor–related protein 1 (LRP1) as an SAA r

Pathogenic <i>Vibrio</i> species cause diseases in diverse marine animals reared in aquaculture. Since their pathogenesis, persistence, and survival in marine environments are regulated by quorum sensing (QS), QS interference has attracted attention as a means to control these bacteria in aquatic settings. A few QS inhibitors of <i>Vibrio</i> species have been reported, but detailed molecular mechanisms are lacking. Here, we identified a novel, potent, and selective <i>Vibrio</i> QS inhibitor, n

Vitamin A is a dietary component that is essential for the development of intestinal immunity. Vitamin A is absorbed and converted to its bioactive derivatives retinol and retinoic acid by the intestinal epithelium, yet little is known about how epithelial cells regulate vitamin A-dependent intestinal immunity. Here we show that epithelial cell expression of the transcription factor retinoic acid receptor β (RARβ) is essential for vitamin A-dependent intestinal immunity. Epithelial RARβ activate

Peroxiredoxins (Prxs) are ubiquitous antioxidant enzymes that reduce toxic peroxides. A new Vibrio vulnificus Prx, named Prx3, was identified and characterized in this study. Biochemical and mutational analyses revealed that Prx3 reduces H2O2, utilizing glutaredoxin 3 (Grx3) and glutathione (GSH) as reductants, and requires only N-terminal peroxidatic cysteine for its catalysis. These results, combined with the monomeric size of Prx3 observed under non-reducing conditions, suggested that Prx3 is

Serum amyloid A (SAA) proteins are strongly induced in the liver by systemic infection and in the intestine by bacterial colonization. In infected mice, SAA proteins circulate in association with the vitamin A derivative retinol, suggesting that SAAs transport retinol during infection. Here we illuminate a structural basis for the retinol-SAA interaction. In the bloodstream of infected mice, most SAA is complexed with high-density lipoprotein (HDL). However, we found that the majority of the cir

Peroxiredoxins (Prxs) are ubiquitous antioxidant enzymes reducing toxic peroxides. Two distinct 2-Cys Prxs, Prx1 and Prx2, were identified in Vibrio vulnificus, a facultative aerobic pathogen. Both Prxs have two conserved catalytic cysteines, C(P) and C(R), but Prx2 is more homologous in amino acid sequences to eukaryotic Prx than to Prx1. Prx2 utilized thioredoxin A as a reductant, whereas Prx1 required AhpF. Prx2 contained GGIG and FL motifs similar to the motifs conserved in sensitive Prxs an

Two peroxiredoxins, Prx1 and Prx2, were previously identified in Vibrio vulnificus. Besides OxyR1, a homologue of Escherichia coli OxyR (EcOxyR), OxyR2 that shares low homology with EcOxyR was first identified in V. vulnificus. OxyR2 activated prx2 during aerobic growth, while OxyR1 activated prx1 only when exposed to exogenous H2O2. OxyR2 was oxidized to form a reversible C206 to C215 disulphide bond by sensing low levels of H2O2, which were insufficient to oxidize OxyR1, and only the oxidized

The human gut houses a diverse and dynamic microbiome critical for digestion, metabolism, and immune development, exerting profound effects on human health. However, these microorganisms pose a potential threat by breaching the gut barrier, entering host tissues, and triggering infections, uncontrolled inflammation, and even sepsis. The intestinal epithelial cells form the primary defense, acting as a frontline barrier against microbial invasion. Antimicrobial proteins (AMPs), produced by these

Increasing antibiotic resistance has led to the development of new strategies to combat bacterial infection. Anti-virulence strategies that impair virulence of bacterial pathogens are one of the novel approaches with less selective pressure for developing resistance than traditional strategies that impede viability. In this study, a small molecule CM14 [N-(4-oxo-4H-thieno[3,4-c]chromen-3-yl)-3-phenylprop-2-ynamide] that inhibits the activity of HlyU, a transcriptional regulator essential for the

Aromatic amino acid (AAA) metabolites, derived from tryptophan, phenylalanine, and tyrosine through coordinated host and microbial metabolism, have emerged as critical modulators of immune function. We examine the complex journey of AAAs from dietary intake through intestinal absorption and metabolic transformation, highlighting the crucial role of host-microbe metabolic networks in generating diverse immunomodulatory compounds. This review provides a unique integrative perspective by mapping th

The bacterial transcriptional regulator OxyR is known to function as a two-state redox switch. OxyR senses cellular levels of H2O2 via a "sensing cysteine" that switches from the reduced to a disulfide state upon H2O2 exposure, inducing the expression of antioxidant genes. The reduced and disulfide states of OxyR, respectively, bind to extended and compact regions of DNA, where the reduced state blocks and the oxidized state allows transcription and further induces target gene expression by inte

Most Gram-negative bacteria respond to excessive levels of H₂O₂ using the peroxide-sensing transcriptional regulator OxyR, which can induce the expression of antioxidant genes to restore normality. <i>Vibrio vulnificus</i> has two distinct OxyRs (OxyR1 and OxyR2), which are sensitive to different levels of H₂O₂ and induce expression of two different peroxidases, Prx1 and Prx2. Although OxyR1 has both high sequence similarity and H₂O<sub>2</s

Enteropathogenic bacteria express two-component systems (TCSs) to sense and respond to host environments, developing resistance to host innate immune systems like cationic antimicrobial peptides (CAMPs). Although an opportunistic human pathogen Vibrio vulnificus shows intrinsic resistance to the CAMP-like polymyxin B (PMB), its TCSs responsible for resistance have barely been investigated. Here, a mutant exhibiting a reduced growth rate in the presence of PMB was screened from a random transposo

The human intestine is home to a dense community of microbiota that plays a key role in human health and disease. Nutrients are essential regulators of both host and microbial physiology and function as key coordinators of host-microbe interactions. Therefore, understanding the specific roles and underlying mechanisms of each nutrient in regulating the host-microbe interactions will be essential in developing new strategies for improving human health through microbiota and nutrient intervention.

<i>Vibrio vulnificus</i>, an opportunistic human pathogen, employs biofilm formation as a key survival and virulence mechanism. BrpT, a transcriptional regulator, is essential for <i>V. vulnificus</i> biofilm development by regulating the expression of biofilm-related genes. In this study, we aimed to identify a small molecule inhibitor of BrpT to combat <i>V. vulnificus</i> biofilm formation. High-throughput screening of 7,251 compounds using an <i>Escherichia coli</i> reporter strain carrying