Microbiology and Immunology最新文献

Cover photograph: Metabolism pathways and epigenetic reprogramming during immune memory. The primary infection triggers the activation of intracellular metabolism pathways such as glycolysis and adenosine metabolism. Some metabolites of these processes, such as acetyl coenzyme A (acetyl-CoA) and S-adenosylmethionine (SAM), might mediate epigenetic reprogramming of gene regulation during innate immune memory. Microbiol Immunol: 67:355–364. Article link here

Defensins and inflammation are innate immune barriers of the body against infectious pathogens. Searching for a compound that can inhibit infectious diseases by affecting human β-defensin (HBD) and proinflammatory cytokines is the new trend in research to control bacterial infection. The aim of this study is to provide a natural compound, Filipendula glaberrima Nakai extract (FGE), which is able to induce the expression of an antimicrobial defensin as well as reduce inflammation. FGE induced the expression of HBD2 and HBD3 through activating both p38 and NF-κB signaling pathways. Furthermore, FGE inhibited the expression of TNF-α and IL-6 via p38 and NF-κB pathways in Staphylococcus aureus–stimulated THP1 cells. Injection of FGE alleviated cutaneous erythema and swelling caused by S. aureus injection in mice ears. Taken together, FGE could reduce bacterial infection by inducing the expression of defensin and anti-inflammatory activity.

Prion diseases are fatal neurodegenerative disorders affecting both humans and animals. The causative agent, prion, is extremely resistant to common disinfection procedures. Thus, effective prion inactivation strategies using relatively safe and less corrosive disinfectants are required. A solution containing CAC-717, mesoscopic crystals of calcium bicarbonate, exerts both antimicrobial and virucidal activities without apparent harmful effects. This study demonstrated that combined treatment with CAC-717 absorbed on ceramic (CAC-717 ceramic) and sodium dodecyl sulfate (SDS) substantially reduced the protein misfolding cyclic amplification (PMCA) seeding activity of Chandler strain scrapie mouse-brain homogenates (ScBH). Additionally, bioassays demonstrated that ScBH-inoculated mice treated with CAC-717 ceramic in combination with sodium dodecyl sulfate (SDS) did not develop disease. Furthermore, this combination effectively inactivated PMCA seeding activity on ScBH-coated stainless-steel wires below the detection limit. Overall, the findings suggest that combined treatment with CAC-717 ceramic and SDS represents a promising and less damaging approach for prion inactivation.

The high mortality rate associated with Listeria monocytogenes can be attributed to its ability to invade the body systemically and to activate inflammasomes. Both of these processes are facilitated by expressing a major virulence factor known as listeriolysin O, a 56 kDa pore-forming protein encoded by the hly gene. Listeriolysin O plays a crucial role in the pathogenesis of the bacterium by facilitating the escape of the pathogen from the phagosome into the cytosol. This process is essential for the successful establishment of infection. In addition, listeriolysin O is known as an immunomodulator that activates host signal transduction. In addition to listeriolysin O, Listeria expresses a variety of bacterial ligands, such as lipoteichoic acid, nucleotide, and flagellin, that are recognized by host intracellular pattern-recognition receptors including Nod-like receptors, AIM2-like receptors, and RIG-I-like receptors. This review introduces intracellular recognition of Listeria monocytogenes since recent studies have revealed that the activation of inflammasome exacerbates Gram-positive bacteria infection.

This review describes the upstream-directed movement in the small parasitic bacterium Mycoplasma. Many Mycoplasma species exhibit gliding motility, a form of biological motion over surfaces without the aid of general surface appendages such as flagella. The gliding motility is characterized by a constant unidirectional movement without changes in direction or backward motion. Unlike flagellated bacteria, Mycoplasma lacks the general chemotactic signaling system to control their moving direction. Therefore, the physiological role of directionless travel in Mycoplasma gliding remains unclear. Recently, high-precision measurements under an optical microscope have revealed that three species of Mycoplasma exhibited rheotaxis, that is, the direction of gliding motility is lead upstream by the water flow. This intriguing response appears to be optimized for the flow patterns encountered at host surfaces. This review provides a comprehensive overview of the morphology, behavior, and habitat of Mycoplasma gliding, and discusses the possibility that the rheotaxis is ubiquitous among them.

A reverse genetics system for the respiratory syncytial virus (RSV), which causes acute respiratory illness, is an effective tool for understanding the pathogenicity of RSV. To date, a method dependent on T7 RNA polymerase is commonly used for RSV. Although this method is well established and recombinant RSV is well rescued from transfected cells, the requirement for artificial supply of T7 RNA polymerase limits its application. To overcome this, we established a reverse genetics system dependent on RNA polymerase II, which is more convenient for the recovery of recombinant viruses from various cell lines. First, we identified human cell lines with high transfection efficiency in which RSV can replicate effectively. Two human cell lines, Huh-7 and 293T, permitted the propagation of recombinant green fluorescent protein–expressing RSV. Our minigenome system revealed that efficient transcription and replication of RSV occurred in both Huh-7 and 293T cells. We then confirmed that recombinant green fluorescent protein–expressing RSV was rescued in both Huh-7 and 293T cells. Furthermore, the growth capability of viruses rescued from Huh-7 and 293T cells was similar to that of recombinant RSV rescued using the conventional method. Thus, we succeeded in establishing a new reverse genetics system for RSV that is dependent on RNA polymerase II.

Multidrug efflux systems of the resistance-nodulation-cell division family play a crucial role in resistance of Pseudomonas aeruginosa to a large variety of antibiotics. Here, we investigated the role of clinically relevant efflux pumps MexAB⁻OprM, MexCD⁻OprJ, and MexXY⁻OprM in resistance against different cationic antimicrobial peptides (AMPs). Our results indicate that a knock-out in efflux pump MexXY-OprM increased susceptibility to some AMPs by two- to eightfold. Our data suggest a contribution of MexXY-OprM in resistance to certain AMPs in P. aeruginosa, which should be considered in the future development of new and highly active antimicrobial peptides to fight multidrug resistant infections.

Coronaviruses (CoVs) have long been known to infect humans, mainly alpha-CoV and beta-CoV. The vaccines developed for SARS-CoV-2 are likely not effective against other coronavirus species, whereas the risk of the emergence of new strains that may cause the next epidemic/pandemic is high. The development of antiviral drugs that are effective across different CoVs represents a viable strategy for improving pandemic preparedness. In this study, we aim to identify pan-coronaviral agents by targeting the conserved main protease (Mpro). For drug screening, the catalytic dyad of four human CoVs (HCoVs: SARS-CoV-2, and seasonal CoV NL63, OC43, and 229E) was targeted by molecular docking. The identified leading candidate theobromine, a xanthine derivative, was further tested in cell culture models of coronavirus infection. Theobromine binds strongly with the catalytic dyad (His41 and Cys144/145) of SARS-CoV-2 and HCoV-NL63 Mpro, mildly with HCoV-OC43, but not with HCoV-229E. However, theobromine only shows dose-dependent inhibition in Calu3 cells inoculated with SARS-CoV-2, but not in cells inoculated with seasonal CoVs. Theobromine exerts antiviral activity against coronavirus infections potentially through targeting Mpro. However, the antiviral potency is distinct among different CoVs.

Acinetobacter baumannii is a multidrug-resistant coccobacillus responsible for severe nosocomial infectious diseases. This study mainly focuses on investigating the antimicrobial resistance features of a clinically isolated strain (A. baumannii CYZ) using the PacBio Sequel II sequencing platform. The chromosomal size of A. baumannii CYZ is 3,960,760 bp, which contains a total of 3803 genes with a G + C content of 39.06%. Functional analysis performed using the Clusters of Orthologous Groups of Proteins (COGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, as well as the Comprehensive Antibiotic Resistance Database (CARD) revealed a complicated set of antimicrobial resistance determinants in the genome of A. baumannii CYZ, which were mainly classified into multidrug efflux pumps and transport systems, β-lactamase relative and penicillin-binding proteins, aminoglycoside modification enzymes, alternation of antibiotic target sites, lipopolysaccharide relative, and other mechanisms. A total of 35 antibiotics were tested for the antimicrobial susceptibility of A. baumannii CYZ, and the organism exhibited a stronger antimicrobial resistance ability. The phylogenetic relationship indicated that A. baumannii CYZ has high homology with A. baumannii ATCC 17978; however, the former also exhibited its specific genome characteristics. Our research results give insight into the genetic antimicrobial-resistant features of A. baumannii CYZ as well as provide a genetic basis for the further study of the phenotype.

Cover photograph: Electron microscopy of lectin-treated SARS-CoV-2. SARS-CoV-2 was concentrated by using a porous membrane-filter unit and incubated with saline or 9 μM OAA, ESA-2, or HypninA-2 for 10 min. The sample was negative-stained and observed by transmission electron microscopy. The left panel for each lectin is a 2000x view, and the right panel is a magnified view of the designated region. The area of n viruses on the electron micrographs was measured and divided into groups corresponding to less than 2 viral particles (~2), 2-5 (2~5), and 5 or more (5~), and the percentages were plotted on a pie chart. For HypninA-2, all virus particles made up about 10 huge clumps, and nothing that appeared to be free virus particles was found. Therefore, no pie chart was drawn. Microbiol Immunol: 67:334–344. Article link here