The human stress hormones catecholamines play a critical role in communication between human microbiota and their hosts and influence the outcomes of bacterial infections. However, it is unclear how M. tuberculosis senses and responds to certain types of human stress hormones. In this study, we screened several human catecholamine stress hormones (epinephrine, norepinephrine, and dopamine) for their effects on Mycobacterium growth. Our results showed that epinephrine significantly stimulated the growth of M. tuberculosis in the serum-based medium as well as macrophages. In silico analysis and molecular docking suggested that the extra-cytoplasmic domain of the MprB might be the putative adrenergic sensor. Furthermore, we showed that epinephrine significantly enhances M. tuberculosis biofilm formation, which has distinct texture composition, antibiotic resistance, and stress tolerance. Together, our data revealed the effect and mechanism of epinephrine on the growth and biofilm formation of M. tuberculosis, which contributes to the understanding of the environmental perception and antibiotic resistance of M. tuberculosis and provides important clues for the understanding of bacterial pathogenesis and the development of novel antibacterial therapeutics.
Tuberculosis (TB), caused by M. tuberculosis (M.tb), is the leading infectious cause of mortality worldwide. The emergence of drug-resistant M.tb has made the control of TB more difficult. In our study, we investigated the ability of microorganism fermentation products from the soil to inhibit M.tb. We successfully identified four fermentation products (Micromonospora chokoriensis, Micromonospora purpureochromogenes, Micromonospora profundi, Streptomyces flavofungini) that inhibited the growth of M.tb in vitro and in intracellular bacteria at 25 μg/mL MIC. Importantly, the fermentation products decreased some essential gene expression levels for M.tb growth. Our data provide the possibility that microbial fermentation products have potential development value for anti-M.tb drugs.
Ascites syndrome (AS) is a metabolic disease that seriously affects the growth and development of broiler chickens. Intestinal microbiota play a significant role in the growth of broiler chickens. Therefore, further research on the relationship between AS and intestinal microbiota will help to better understand the impact of AS on broiler growth. In this study, 0.2% sodium chloride was added to the drinking water, which induced AS in broiler chickens, and we detected the influence of AS on the growth performance and cecal microbiota of broiler chickens. The results showed that AS significantly reduced the cecal microbial diversity of broiler chickens and affected the cecal microbial composition at the phylum and genus levels (p = 0.05). Further, LEfSe analysis revealed that AS significantly increased the abundance of Bacteroidetes (p = 0.035) while simultaneously reducing the abundance of Actinobacteria (p = 0.031) in the cecum. Additionally, the differential metabolites associated with polycyclic aromatic hydrocarbon degradation were significantly diminished. The findings suggest that AS may further impact the growth rate of broiler chickens by altering cecal microorganisms.
The virulence of Mycobacterium tuberculosis (M. tuberculosis) is related to many factors, including intracellular survival, cell wall permeability, and cell envelope proteins. However, the biological function of the M. tuberculosis membrane protein Rv1476 remains unclear. To investigate the potential role played by Rv1476, we constructed an Rv1476 overexpression strain and found that overexpression of Rv1476 enhanced the intracellular survival of M. tuberculosis, while having no impact on the growth rate in vitro. Stress experiments demonstrated that the Rv1476 overexpression strain displayed increased susceptibility to different stresses compared to the wild-type strain. Transcriptome analysis showed that Rv1476 overexpression causes changes in the transcriptome of THP-1 cells, and differential genes are mainly enriched in cell proliferation, fatty acid degradation, cytokine–cytokine receptor interaction, and immune response pathways. Rv1476 overexpression inhibited the expression of some anti-tuberculosis-related genes, such as CCL1, IL15, IL16, ISG15, GBP5, IL23, ATG2A, IFNβ, and CSF3. Altogether, we conclude that Rv1476 may play a critical role for M. tuberculosis in macrophage survival.
Newly synthesized Ren’s oligopeptides-1 was found to have an antiviral effect in clinical trials, and the purpose of this study was to further demonstrate the antiviral activity of Ren’s oligopeptides-1 against the PRV 152-GFP strain. We used the real-time cell analysis system (RTCA) to detect the cytotoxicity of different concentrations of Ren’s oligopeptides-1. We then applied high content screening (HCS) to detect the antiviral activity of Ren’s oligopeptides-1 against PRV. Meanwhile, the fluorescence signal of the virus was collected in real time and the expression levels of the related genes in the PK15 cells infected with PRV were detected using real-time PCR. At the mRNA level, we discovered that, at a concentration of 6 mg/mL, Ren’s oligopeptides-1 reduced the expression of pseudorabies virus (PRV) genes such as IE180, UL18, UL54, and UL21 at a concentration of 6 mg/mL. We then determined that Ren’s oligopeptides-1 has an EC50 value of 6 mg/mL, and at this level, no cytotoxicity was observed.