In vibrios, the expression of virulence factors is often controlled by LuxR, the master quorum-sensing regulator. Here, we investigate the interplay between LuxR and σ^E, an alternative sigma factor, during the control of virulence-related gene expression and adaptations to temperature elevations in the zoonotic pathogen Vibrio alginolyticus. An rpoE null V. alginolyticus mutant was unable to adapt to various stresses and was survival-deficient in fish. In wild type V. alginolyticus, the expression of LuxR-regulated virulence factors increased as the temperature was increased from 22°C to 37°C, but mutants lacking σ^E did not respond to temperature, indicating that σ^E is critical for the temperature-dependent upregulation of virulence genes. Further analyses revealed that σ^E binds directly to -10 and -35 elements in the luxR promoter that drive its transcription. ChIP assays showed that σ^E binds to the promoter regions of luxR, rpoH and rpoE at high temperatures (e.g., 30°C and 37°C). However, at higher temperatures (42°C) that induce thermal stress, σ^E binding to the luxR promoter decreased, while its binding to the rpoH and rpoE promoters was unchanged. Thus, the temperature-dependent binding of σ^E to distinct promoters appears to underlie a σ^E-controlled switch between the expression of virulence genes and adaptation to thermal stress. This study illustrates how a conserved temperature response mechanism integrates into quorum-sensing circuits to regulate both virulence and stress adaptation. Zoonotic Vibrio outbreaks are believed to be closely associated with increases in environmental temperature. The mechanisms underlying this phenomenon have not been defined. Here, we show that the expression of the V. alginolyticus exotoxin Asp and other quorum-sensing (QS)-regulated virulence factors are induced by increasing temperatures, with the maximum expression observed at approximately 37°C. σ^E plays an essential role in regulating the QS master regulator LuxR in response to temperature shifts by binding directly to the -10 and -35 regions of the luxR promoter to drive its transcription. However, at higher thermal stress temperatures, σ^E binding to the luxR promoter decreased, resulting in a reduction in luxR transcription. This change underlies a binomial switch mechanism that regulates σ^E-controlled virulence gene expression patterns. Furthermore, we found that anti-σ^E signaling was involved in this stress and virulence reciprocal switch. This study suggests that a common temperature response mechanism is integrated into QS circuits to regulate both virulence and adaptation in related Vibrio taxa.

The microbiota profile of children changes with age. To investigate the differences in the gut microbiota profile of 1- and 4-year-old children, we collected fecal samples and sequenced the V3–V4 hypervariable region of the 16S rRNA gene via high-throughput DNA sequencing. From phylum to species level, the microbiota underwent significant changes with age. The abundance of phyla Proteobacteria and Actinobacteria declined with age, whereas phyla Firmicutes and Bacteroidetes increased with age and dominated the gut microbiota of 4-year-olds. The intestinal environment of children at age four is closer to maturity. Hence, the abundance of Bifidobacterium significantly decreased in the gut of 4-year-olds, whereas Akkermansia muciniphila increased from 0.14% in 1-year-olds to 4.25% in 4-year-olds. The functional change in gut microbiota is consistent with changes in infant food, as microbiota participating in amino acid and vitamin metabolism were enriched in 1-year-olds, whereas microbiota involved in lipid metabolism increased with age.

Elemental sulfur has been used as a traditional Chinese medicine to treat the late-onset hypogonadism and impotence without a clarified mechanism for many hundreds of years. In the present study, mice were received sulfur or distilled water for 35 days by daily intragastric gavage at a dose of 250 mg/kg body weight. Then, the serum testosterone level and genes associated with testicular testosterone biosynthesis (TTB) were detected. The gut microbiota was also analyzed by 16S rRNA gene sequencing. Serum testosterone level was significantly increased by 291.1% in sulfur-treated mice. The H2S levels in serum and feces were significantly increased. The expression of genes associated with TTB including StAR, p450c17, 3β-HSD, and P450scc in testes were significantly upregulated by Sulfur and NaHS, suggesting that sulfur promotes TTB depending on H2S. In addition, sulfur increased the diversity of gut microbiota and the abundance of several bacteria associated with sulfur metabolism, including genus Prevotella, which might be positively associated with serum level of testosterone in boys. Five pathways including bile secretion, carotenoid biosynthesis, lipid biosynthesis proteins, propanoate metabolism, and biosynthesis of type II polyketide products, were identified to associate with sulfur. Together, our results suggested that sulfur upregulated testicular testosterone biosynthesis via H2S, which was associated with alteration of gut microbiota in mice. Our study highlights a mechanism for the treatment of late-onset hypogonadism and impotence by sulfur.