This review summarizes current knowledge regarding the pathological mechanism of Streptococcus pneumoniae, a major cause of pneumonia, sepsis, and meningitis, with focus on our previously presented studies.To identify pneumococcal adhesins or invasins on cell surfaces, we investigated several proteins with an LPXTG anchoring motif and identified one showing interaction with human fibronectin, which was designated PfbA. Next, the mechanism of pneumococcal evasion form host immunity system in blood was examined and pneumococcal α-Enolase was found to function as a neutrophil extracellular trap induction factor. Although S. pneumoniae organisms are partially killed by iron ion-induced free radicals, they have an ability to invade red blood cells and then evade antibiotics, neutrophil phagocytosis, and H2O2 killing. In addition, our findings have indicated that zinc metalloprotease ZmpC suppresses pneumococcal virulence by inhibiting bacterial invasion of the central nervous system. Since evolutionarily conserved virulence factors are potential candidate therapeutic targets, we performed molecular evolutionary analyses, which revealed that cbpJ had the highest rate of codons under negative selection to total number of codons among genes encoding choline-binding proteins. Our experimental analysis results indicated that CbpJ functions as a virulence factor in pneumococcal pneumonia by contributing to evasion of neutrophil killing.Use of a molecular biological approach based on bacterial genome sequences, clinical disease states, and molecular evolutionary analysis is an effective strategy for revealing virulence factors and important therapeutic targets.
Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes serious acute, persistent, and relapsing infections. Recent year, the effectiveness of antibiotics for eliminating P. aeruginosa infections has been further complicated by the emergence of multidrug-resistant strains. Thus, new approaches for the rapid detection and novel antimicrobial drug discovery are urgently needed to control such intractable infections caused by the pathogen. Also, we do need deep understanding of the drug resistance mechanisms to overcome this issue. Here I describe a brief review on my biological studies toward controlling infectious diseases caused by multidrug-resistant P. aeruginosa.
Autophagy acts as an intracellular host defense system against invading pathogenic microorganisms such as Group A Streptococcus (GAS). Autophagy is a membrane-mediated degradation system that is regulated by intracellular membrane trafficking regulators, including small GTPase Rab proteins. Here, we revealed Rab GTPase network that regulate autophagosome formation against GAS. A unique set of Rab GTPases coordinates autophagy to enable to form huge autophagosomes surrounding GAS by linking recycling endosomes and trans Golgi-network. We also found that NLRP4, one of intracellular pathogen recognition receptor, directs Rho signaling to facilitate autophagosome formation. In this article, we would like to show our findings on how host autophagy regulators coordinate autophagy during GAS infection.
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