Finkhunter8721

The glycolytic enzyme and bacterial virulence factor of Listeria monocytogenes, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH, Lmo2459), ADP-ribosylated the small GTPase, Rab5a, and blocked phagosome maturation. This inhibitory activity localized within the NAD binding domain of GAPDH at the N-terminal 1-22 peptides, also conferred listeriosis protection when used in dendritic cell-based vaccines. In this study, we explore GAPDH of Listeria, Mycobacterium, and Streptococcus spp. taxonomic groups to search for epitopes that confer broad protection against pathogenic strains of these bacteria. GAPDH multivalent epitopes are selected if they induce inhibitory actions and wide-ranging immune responses. Proteomic isolation of GAPDH from dendritic cells infected with Listeria, Mycobacterium, or Streptococcus confirmed similar enzymatic, Rab5a inhibitory and immune stimulation abilities. We identified by bioinformatics and functional analyses GAPDH N-terminal 1-22 peptides from Listeria, Mycobacterium, and Streptococcus that shared 95% sequence homology, enzymatic activity, and B and T cell immune domains. Sera obtained from patients or mice infected with hypervirulent pathogenic Listeria, Mycobacterium, or Streptococcus presented high levels of anti-GAPDH 1-22 antibodies and Th2 cytokines. Monocyte derived dendritic cells from healthy donors loaded with GAPDH 1-22 peptides from Listeria, Mycobacterium, or Streptococcus showed activation patterns that correspond to cross-immunity abilities. In summary, GAPDH 1-22 peptides appeared as putative candidates to include in multivalent dendritic based vaccine platforms for Listeria, Mycobacterium, or Streptococcus.Overuse or abuse of antibiotics has undoubtedly accelerated the increasing prevalence of global antibiotic resistance crisis, and thus, people have been trying to explore approaches to decrease dosage of antibiotics or find new antibacterial agents for many years. Antimicrobial peptides (AMPs) are the ideal candidates that could kill pathogens and multidrug-resistant bacteria either alone or in combination with conventional antibiotics. In the study, the antimicrobial efficacy of mud crab Scylla paramamosain AMPs Sphistin and Sph12-38 in combination with eight selected antibiotics was evaluated using a clinical pathogen, Pseudomonas aeruginosa. It was interesting to note that the in vitro combination of rifampicin and azithromycin with Sphistin and Sph12-38 showed significant synergistic activity against P. aeruginosa. Moreover, an in vivo study was carried out using a mouse model challenged with P. aeruginosa, and the result showed that the combination of Sph12-38 with either rifampicin or azithromycin could significantly promote the healing of wounds and had the healing time shortened to 4-5 days compared with 7-8 days in control. The underlying mechanism might be due to the binding of Sphistin and Sph12-38 with P. aeruginosa lipopolysaccharides (LPS) and subsequent promotion of the intracellular uptake of rifampicin and azithromycin. Taken together, the significant synergistic antibacterial effect on P. aeruginosa in vitro and in vivo conferred by the combination of low dose of Sphistin and Sph12-38 with low dose of rifampicin and azithromycin would be beneficial for the control of antibiotic resistance and effective treatment of P. aeruginosa-infected diseases in the future.In 2019, the United States Food and Drug Administration accorded restricted approval to Sanofi Pasteur's Dengvaxia, a live attenuated vaccine (LAV) for dengue fever, a mosquito-borne viral disease, caused by four antigenically distinct dengue virus serotypes (DENV 1-4). The reason for this limited approval is the concern that this vaccine sensitized some of the dengue-naïve recipients to severe dengue fever. Recent knowledge about the nature of the immune response elicited by DENV viruses suggests that all LAVs have inherent capacity to predominantly elicit antibodies (Abs) against the pre-membrane (prM) and fusion loop epitope (FLE) of DENV. These antibodies are generally cross-reactive among DENV serotypes carrying a higher risk of promoting Antibody-Dependent Enhancement (ADE). ADE is a phenomenon in which suboptimal neutralizing or non-neutralizing cross-reactive antibodies bind to virus and facilitate Fcγ receptor mediated enhanced entry into host cells, followed by its replication, and thus increasing tfic EDIII antibodies may be more directly related to protection from disease in the absence of ADE promoted by the cross-reactive antibodies.Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by neuronal loss and dysfunction of dopaminergic neurons located in the substantia nigra, which contain a variety of misfolded α-synuclein (α-syn). Medications that increase or substitute for dopamine can be used for the treatment of PD. Recently, numerous studies have shown gut microbiota plays a crucial role in regulating and maintaining multiple aspects of host physiology including host metabolism and neurodevelopment. In this review article, the role of gut microbiota in the etiological mechanism of PD will be reviewed. Furthermore, we discussed current pharmaceutical medicine-based methods to prevent and treat PD, followed by describing specific strains that affect the host brain function through the gut-brain axis. We explained in detail how gut microbiota directly produces neurotransmitters or regulate the host biosynthesis of neurotransmitters. The neurotransmitters secreted by the intestinal lumen bacteria may induce epithelial cells to release molecules that, in turn, can regulate neural signaling in the enteric nervous system and subsequently control brain function and behavior through the brain-gut axis. Finally, we proved that the microbial regulation of the host neuronal system. Endogenous α-syn can be transmitted long distance and bidirectional between ENS and brain through the circulatory system which gives us a new option that the possibility of altering the community of gut microbiota in completely new medication option for treating PD.The skin represents the exterior interface between the human body with the environment while providing a home to trillions of the commensal microorganisms-collectively referred to as the skin microbiota. These microbes that coexist in an established balance play a pivotal role in the protection of cutaneous health and the orchestration of skin homeostasis. However, the well-controlled but delicate balance can be perturbed by alterations in the skin microbial communities, namely, dysbiosis, often due to commensals defeated by pathogens competing for space and nutrients, which leads to the occurrence of multiple cutaneous disorders. In view of this, the analysis of skin microbiota constituents in skin diseases is crucial for defining the role of commensal microbes and treatment of skin diseases. Selleck Tulmimetostat Emerging evidence shows that the ecology-based therapy of microbial transplantation has been proven as a valid therapeutic strategy for cutaneous disorders caused by skin microbial dysbiosis. Although its mechanism is not well-understood, there are already some applications for ecology-based therapy with the aim of correcting the imbalances on the cutaneous ecosystem.