Sawyerhinson2159

Mycoplasma genitalium is a small size, sexually transmitted bacterial pathogen that causes urethritis in males and cervicitis in females. Being resistant to antibiotics, difficulty in diagnosis, treatment, and control of this cosmopolitan infection, vaccination is the alternating method for its effective management. Herein, this study was conducted to computationally design a multi-epitope vaccine to boost host immune responses against M. genitalium. To achieve the study aim, immunoinformatics approaches were applied to the said pathogen's proteomics sequence data. B and T cell epitopes were projected from the three shortlisted vaccine proteins; MG014, MG015, Hmw3MG317. learn more The final vaccine ensemble comprises cytotoxic and helper T cell epitopes fused through appropriate linkers. The epitopes peptide is then liked to an adjuvant for efficient recognition and processing by the host immune system. The various physicochemical parameters such as allergenicity, antigenicity, theoretical pI, GRAVY, and molecular weight of the vaccine were checked and found safe and effective to be used in post-experimental studies. The stability and binding affinity of the vaccine with the TLR1/2 heterodimer were ensured by performing molecular docking. The best-docked complex was considered, ranked top having the lowest binding energy and strong intermolecular binding and stability. Finally, the vaccine constructs better expression was obtained by in silico cloning into the pET28a (+) vector in Escherichia coli K-12 strain, and immune simulation validated the immune response. In a nutshell, all these approaches lead to developing a multi-epitope vaccine that possessed the ability to induce cellular and antibody-mediated immune responses against the pathogen used.Uropathogenic Escherichia coli (UPEC) is the most common pathogen causing urinary tract infections (UTIs). The pathogenesis of UPEC relies on the formation of intracellular bacterial communities (IBCs) after invading bladder epithelial cells (BECs). In this study, the gene expression profiles of UPEC after invading BECs were comprehensively analyzed using RNA sequencing to reveal potential virulence-related genes. The small protein MgtS, which is transcriptionally upregulated in BECs, was further investigated. It was found that MgtS contributed positively to UPEC invasion of BECs and colonization in murine bladders. A two-component regulatory system, PhoPQ was confirmed as a direct activator of mgtS expression in BECs, and magnesium limitation is proposed as a host cue for the activation. This study provides the first comprehensive analysis of the transcriptome profile of UPEC during its intra-BECs life, revealing a new virulence-associated gene and its regulatory mechanism.

Enterococcus faecalis is the bacterial species closely related to persistent infection in root canals. Interleukin-1 beta (IL-1β) is the most commonly detected proinflammatory cytokine in periapical granulation tissue and plays a critical role in host defenses against microbial infection. The synthesis and secretion of IL-1β are mediated mainly by Toll-like receptors and inflammasome activation. The previous study found that the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and the absent in Melanoma 2 (AIM2) inflammasomes are positively expressed in periapical granulation tissue. The aim of this study was to investigate the pathogenicity of E. faecalis and the molecular mechanisms of IL-1β secretion by THP-1 macrophages infected with E. faecalis.

The IL-1β and lactate dehydrogenase (LDH) levels induced by E. faecalis were investigated with enzyme-linked immunosorbent assay (ELISA) kit and cytotoxicity assay kit, caspase-1 and inflammasome expression levels were investigated usused by E. faecalis.

E. faecalis infection activated caspase-1 and the NLRP3 inflammasome to induce IL-1β secretion and inflammatory cell death (pyroptosis). Furthermore, the activation and expression of NLRP3 induced by E. faecalis required P2X7R and K+ efflux. This study furthers our understanding of the inflammatory response mechanism induced by E. faecalis indicates that NLRP3 may be a potential target for treatment and prevention of persistent periodontitis caused by E. faecalis.Enterobacter hormaechei is a foodborne pathogen responsible for neonatal sepsis in humans and respiratory disease in animals. In this work, a new virulent phage (P.A-5) infecting E. hormaechei was isolated from domestic sewage samples and characterized. Transmission electron microscopy revealed that P.A-5 belonged to the family Myoviridae having a head size of 77.53 nm and a tail length of 72.24 nm. The burst size was 262 PFU/cell after a latent period of 20 min. Phage P.A-5 was able to survive in a pH range of 4-9 and resist temperatures up to 55 °C for 60 min. The genome sequence of P.A-5 had homology most similar to that of Shigellae phage MK-13 (GenBank MK509462.1). Pork artificially contaminated with E. hormaechei was used as a model to evaluate the potential of P.A-5. The results clearly showed that P.A-5 treatment can completely inhibit E. hormaechei growth in pork within 8 h, indicating the potential use of P.A-5 as a biocontrol agent for E. hormaechei.Tuberculosis (TB) is the first cause of death by a single infectious agent. Previous reports have highlighted the presence of platelets within Tb granulomas, albeit the immune-associated platelet response to Mycobacterium tuberculosis (Mtb) has not been deeply studied. Our results showed that platelets are recruited into the granuloma in the late stages of tuberculosis. Furthermore, electron-microscopy studies showed that platelets can internalize Mtb and produce host defense peptides (HDPs), such as RNase 7, HBD2 and hPF-4 that bind to the internalized Mtb. Mtb-infected platelets exhibited higher transcription and secretion of IL-1β and TNF-α, whereas IL-10 and IL-6 protein levels decreased. These results suggest that platelets participate in the immune response against Mtb through HDPs and cytokines production.Till date millions of people are infected by SARS-CoV-2 throughout the world, while no potential therapeutics or vaccines are available to combat this deadly virus. Blocking of human angiotensin-converting enzyme 2 (ACE-2) receptor, the binding site of SARS-CoV-2 spike protein, an effective strategy to discover a drug for COVID-19. Herein we have selected 24 anti-bacterial and anti-viral drugs and made a comprehensive analysis by screened them virtually against ACE-2 receptor to find the best blocker by molecular docking and molecular dynamics studies. Analysis of results revealed that, Cefpiramide (CPM) showed the highest binding affinity of -9.1 kcal/mol. Furthermore, MD study for 10 ns and evaluation of parameters like RMSD, RMSF, radius of gyration, solvent accessible surface area analysis confirmed that CPM effectively binds and blocks ACE-2 receptor efficiently.