Nihon saikingaku zasshi. Japanese journal of bacteriology最新文献

Clostridium perfringens type A causes gas gangrene, which is a serious disease caused by wound infection. α-Toxin produced by C. perfringens is known to be the primary pathogenic factor of gas gangrene. Although it has been proposed to induce tissue damage by impairing the host immune system and peripheral circulation, sufficient findings have not been obtained to explain the high virulence of C. perfringens. For the purpose of elucidating the pathogenic mechanism of this bacterium, I focused on the disease progressions such as the bacterial colonization, muscle tissue destruction and repair, and sepsis. In this review, focusing on the action of α-toxin, it will be explained together with the latest research results that the toxin suppresses the activation of the host immune response, represents toxicity to vascular endothelial cells, induces peripheral circulatory disorders due to hematopoietic disorders, inhibits muscle tissue repair, and induces excessive immune response. These mechanisms suggest that α-toxin acts in multiple steps to disrupt host defense and that C. perfringens attacks the host with a highly sophisticated mechanism. It is expected that the onset mechanism of gas gangrene would be elucidated, and I hope that new therapeutic strategies are developed.

Staphylococcus aureus food poisoning was shown by Dack et al. in 1930 to be caused by staphylococcal enterotoxin (SE) produced by S. aureus, rather than by the bacterial infection. However, the emetic mechanism of SE has remained unclear. In this study, we analyzed the emetic activity of SE in several emetic animal models and tried to elucidate the mechanism of emesis. We established a small primate, common marmoset, as a novel emetic model for SE. We also analyzed the immunofluorescence analysis of the gastrointestinal tract of the common marmoset and found that SE binds to submucosal mast cells in the gastrointestinal tract and SE induces degranulation of the mast cells. Furthermore, we showed that SE induces histamine releases, which is inhibited by mast cell stabilizer. In addition, treatment of common marmosets with either mast cell stabilizer or histamine H₁ receptor antagonists suppressed the emetic response induced by SE. These results indicate that orally administered SE binds to submucosal mast cells in the gastrointestinal tract and causes degranulation, resulting in the release of histamine, which in turn causes emesis.

Antimicrobial resistance in bacterial infections is a major concern for clinical settings. In recent years, the number of Extended-spectrum β-lactamase producing (ESBL)- and fluoroquinolones (FQ)-resistant Escherichia coli has been increasing in Japan, especially against third-generation cephalosporins and FQs, which are frequently used in medical practice. On the other hand, antimicrobial agents such as tazobactam-piperacillin, colistin, and tigecycline, which are not general-purpose agents but last-line drugs for multidrug-resistant bacteria, are also important. Enterobacteriaceae that are resistant to these antimicrobials have been reported, although the isolation rate of resistant bacteria is lower than that of frequent used antimicrobial resistance. The author has been studying antimicrobial drug resistance and multidrug resistance of bacteria isolated from clinical settings. In particular, bacteriological analysis of antimicrobial resistance, which is important for treatment, has been conducted mainly on E. coli isolated from clinical specimens at medical facilities in Sapporo City. In this article, the author describes the findings obtained so far.

Countless numbers of bacteria inhabit the intestinal tract. One of the important functions of gut microbiota is the "colonization resistance" against infection by pathogenic microorganisms. However, detailed mechanism of the colonization resistance of intestinal bacteria is still largely unknown. We tried to identify molecular and cellular mechanism of it and found that antigen presentation by dendritic cells is required for the induction of intestinal segmented filamentous bacteria (SFB)-induced T helper 17 (Th17) cells that contribute to the protection against infection by Citrobacter rodentium. We further identified that gut Th17 cells selectively recognize antigens derived from SFB. We also revealed that SFB induce α1,2-fucose, one of carbohydrate chains, expressed on the intestinal epithelial cells mediated by group 3 innate lymphoid cells. Epithelial α1,2-fucose protected against infection by pathogenic bacterium Salmonella typhimurium. Furthermore, it was found that intestinal bacteria inhibit colonization of the pathogenic fungus Candida albicans as well as pathogenic bacteria. From these studies, detailed mechanism of "colonization resistance" against pathogenic microorganisms by intestinal bacteria has been clarified.

Vibrio parahaemolyticus, one of the Gram-negative common enteric pathogens, was first isolated in Japan in 1950. Since its discovery, this bacterium has been a major cause of food-poisoning in Japan, and its infection has recently undergone a global expansion. V. parahaemolyticus possesses a classical exotoxin, thermostable direct hemolysin, and two sets of type III secretion systems (T3SSs) that are able to inject effectors directly into host cells, which are its key virulence factors. Exotoxin/effector is exploited by many Gram-negative pathogens, and plays critical roles in pathogenesis by damaging host cells or by modulating host cell functions, through its activity on/in host cells. In recent years, functional activities of T3SS effectors produced by V. parahaemolyticus have been extensively studied, which has substantially increased our understanding of the pathogenic mechanisms of the bacterium. In paricular, some T3SS effectors of V. parahaemolyticus act as cytotoxins and thereby damage host cells. Here, I focus on these cytotoxic effectors of V. parahaemolyticus and describe recent advances in our understanding of their mechanisms of action.

Bacteria can move or swim by flagella. On the other hand, the motile ability is not necessary to live at all. In laboratory, the flagella-deficient strains can grow just like the wild-type strains. The flagellum is assembled from more than 20 structural proteins and there are more than 50 genes including the structural genes to regulate or support the flagellar formation. The cost to construct the flagellum is so expensive. The fact that it evolved as a motor organ means even at such the large cost shows that the flagellum is essential for survival in natural condition. In this review, we would like to focus on the flagella-related researches conducted by the authors and the flagellar research on Vibrio spp.