Pathogenic streptococcal species are responsible for a broad spectrum of human diseases ranging from non-invasive and localized infections to more aggressive and life-threatening diseases, which cause great economic losses worldwide. Streptococci possess a dozen two-component systems (TCSs) that play important roles in the response to different environmental changes and adjust the expression of multiple genes to successfully colonize and infect host cells. In this review, we discuss the progress in the study of a conserved TCS named CiaRH in pathogenic or opportunistic streptococci including Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus mutans, Streptococcus gordonii, Streptococcus sanguinis, and Streptococcus suis, focusing on the function and regulatory networks of CiaRH, which will provide a promising strategy for the exploration of novel antistreptococcal therapies. This review highlights the important role of CiaRH and provides an important basis for the development of antistreptococcal drugs and vaccines.

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Chlorogenic acid (CGA), one of the most abundant polyphenols in the human diet, exhibits many biological properties, including antibacterial properties. Numerous studies have investigated the antibacterial effects of CGA, however, the molecular mechanisms governing its effects against Streptococcus pyogenes have not been fully elucidated. S. pyogenes is a gram-positive pathogen that causes a wide range of human infections and postinfectious immune-mediated disorders. In this study, we used an iTRAQ-based proteomic technique to investigate the underlying mode of action of CGA against S. pyogenes. KEGG and GO analyses indicated that CGA affected the expression of proteins alterations involved in multiple pathways, downregulating the expression of ribosomal proteins, and upregulating the expression of proteins associated with fatty acid metabolism, pyruvate metabolism and propanoate metabolism, while activating the expression of oxidation-reduction related proteins. Moreover, further cell-based experiments verified that CGA scavenges intracellular ROS in S. pyogenes. These results suggest that CGA may exert its antibacterial action through several actions, such as downregulating ribosomal subunits, affecting lipid metabolism and scavenging intracellular ROS. The results of this study may help to elucidate the molecular mechanisms by which CGA combats pathogens.

Streptococcus pyogenes is one of the main pathogenic bacteria that causes disease in humans. It is reported that over 18 million cases of S. pyogenes disease occurred in the world, and more than 500,000 deaths occur annually worldwide. An effective vaccine is widely regarded as the most reliable way to control and prevent streptococcal infections. However, there is currently no approved vaccine for S. pyogenes. In this study, we evaluated the potential of lipoprotein FtsB as a new vaccine candidate to prevent S. pyogenes infection. Mice vaccinated with purified FtsB protein elicited high titers of IgG, IgG1 and IgG2a antibodies in mouse serum. Vaccinated with FtsB can reduce bacterial systemic dissemination in the blood, heart, and spleen and reduce organ damage in the mouse bacteremia model. In addition, active immunization with FtsB protected against streptococcal abscess formation. Furthermore, immunization with FtsB was efficient in inducing a mixed cellular immune response and promoting the maturation of dendritic cells in mice. The lipoprotein HtsA was served as a positive control because it has been reported to protect mice from S. pyogenes infection in both active and passive immunization. These findings demonstrated that lipoprotein FtsB may serve as a candidate vaccine for the prevention of S. pyogenes infection.

Background and objectives: Houttuynia cordata Thunb, which is a traditional Chinese herbal medicine, is commonly used as an anti-inflammatory, antiviral, and antibacterial agent in China. Emerging evidence shows that extracts of H. cordata Thunb have anticancer activity in human colorectal, leukemic, lung, and liver cancer cells; however, the specific active ingredients or compounds that responsible for these anticancer activities and their mechanism of action remain unknown. Sodium new houttuyfonate (SNH) is an additional product of the active ingredient houttuynin from H. cordata Thunb, which possesses anticancer activity; however, the molecular mechanisms that underlie its action have not been clarified. This study aims to explore the antitumor effect and related molecular mechanism of SNH on human non-small cell lung cancer (NSCLC). Methods:The cytotoxicity of SNH against human lung cancer cells H1299 was investigated using WST-1 and apoptotic assays, and its antitumor molecular mechanism was explored using quantitative proteomics combined with various cellular and biochemical assays. Results:The results showed that SNH reduced the viability and enhanced the apoptosis of H1299 cells in a dosedependent manner. Quantitative proteomics and ingenuity pathway analysis revealed that SNH downregulated the expression of cell cycle-related proteins, which included cyclin-dependent kinase 1 (CDK1), protein tyrosine phosphatase type IVA 2 (PTP4A2), and cyclin-dependent kinase 6 (CDK6), and upregulated the expression of Nrf2 (nuclear factor erythroid 2-related factor 2)-mediated oxidative stress response-related proteins in H1299 cells.Conclusions: SNH-induced G0/G1 arrest and apoptosis in H1299 cells by the inhibition of cell cycle-related proteins that included CDK1, PTP4A2, CDK6, and activated the expression of Nrf2-mediated oxidative stress response-related proteins. These findings might provide new molecular mechanisms that underlie the antitumor activity of SNH against NSCLC and could implicate SNH as a novel therapeutic drug for NSCLC in the future.

CFDC was the first FDA-approved siderophore cephalosporin antibiotic in 2019 and is known for its Trojan horse tactics and broad antimicrobial activity against Gram-negative bacteria. However, its antibacterial mechanism is not fully understood, and whether it has an impact on in vivo iron ion homeostasis remains unknown.