Pathogenic bacteria and host defense system have been evolved by their offense and defense. In vivo research is crucial for elucidation of interactions between them. I have investigated their offence and defense by various standpoints using mouse models of Listeria monocytogenes and Staphylococcus aureus infections. Herein, the results of my research including the roles of endogenous cytokines in host defense, the attenuation of host defense mechanism in obesity and diabetes, the development of vaccines against S. aureus infection by staphylococcal enterotoxin (SE) family molecules, and the emesis-inducing mechanism of SEA are described.
Staphylococcus aureus causes various diseases against humans, including skin infection, pneumonia, food poisoning, and meningitis. Methicillin-resistant S. aureus (MRSA) is resistant to a broad range of antibiotics, causing serious clinical problems. In this review, I summarize our studies to evaluate S. aureus virulence and identify novel virulence regulators. First, we utilized silkworms as an infection model of S. aureus and identified novel virulence factors of S. aureus. Some of the virulence factors interact with RNA in bacterial cells and regulate the expression of virulence factors. Second, we found that S. aureus cells spread on soft agar plates and form a giant colony. We call this phenomenon colony-spreading. High virulence community-acquired MRSA exhibits higher colony-spreading activity than hospital-associated MRSA. The difference in colony spreading is attributed to a specific gene in the mobile genetic element SCCmec carried by hospital-associated MRSA. The gene transcription product inhibits translation of a master regulator against S. aureus virulence genes, resulting in the attenuation of colony-spreading, exotoxin production, and animal killing ability.
Legionella are gram-negative bacteria ubiquitously found in freshwater and soil environments. Once inhaled by humans, Legionella infection could result in a severe form of pneumonia known as Legionellosis. Legionella translocate ~300 effector proteins into host cells via the Dot/Icm type IV secretion system, which is central to Legionella pathogenesis. Here I describe a brief review on recent advances in research on the molecular basis of Legionella—eukaryotic-cell interaction.
Mycobacterium tuberculosis is an intracellular bacterium that can proliferate within phagocytosed macrophages. M. tuberculosis gains this ability by inhibiting phagolysosome biogenesis. On the other hand, autophagy induction can eliminate infected mycobacteria in macrophages. Numerous reports have demonstrated the mechanism of membrane trafficking in macrophages infected with mycobacteria to elucidate how M. tuberculosis proliferates within macrophages. In this review, we make a commentary on the molecular dissection of M. tuberculosis-containing phagosomes demonstrating which host factors constitute the replication niche for mycobacteria, and approach the real images of mycobacterial phagosomes.
Spirochetes have flagella within the cell body and swim by wriggling the spiral cell body. Besides they have been known to be critical agents causing various infectious diseases, their eccentric appearances and motilities have been attracting many scientists in a wide variety of fields other than bacteriologists. Unlike externally flagellated bacteria that swim by using flagella as a screw propeller, spirochetes progress in a liquid by changing their cell shapes. To understand the unique motion mechanism of spirochetes, many experiments and theoretical studies are being carried out. In this review, I will summarize morphological and motile properties of various species of spirochete, such as Borrelia, Treponema and Brachyspira. I will also expound on the motion mechanism of Leptospira with our latest results obtained by high-resolution optical photometry.
Most of our current knowledge about the gene regulation of pathogen comes from studies with in vitro conditions that mimic their host environments, revealing many types of virulence genes and their regulatory network. Recent advances in DNA sequencing and techniques for transcriptome analysis allow us to identify pathogenic genes specifically expressed in vivo. Analyses for gene expression of pathogens in response to the host environment, including immune response and change of bacterial flora during infection, provide clues to understanding the underlying events to establish the infectious diseases. Here, we would like to introduce next epoch-making ideas and concepts to understand the real picture of microbial infection through the recent works of gene regulation in host environments.