Host cells remodel membrane trafficking pathways in response to microbial invasion as a self-defense strategy. Using an epithelial infection model of Group A Streptococcus (GAS), we have elucidated how Rab GTPase networks dynamically reorganize membrane trafficking to govern the intracellular fate of invading bacteria during infection. Our membrane dynamics analyses of selective autophagy (xenophagy) targeting cytosolic GAS revealed that multiple inter-organelle interactions mediated by an infection-specific Rab repertoire are crucial for antibacterial activity. While GAS-secreted NADase inhibits the canonical PI3P-dependent autophagy pathway, the host counters infection by activating an alternative PI4P-dependent xenophagy pathway through Rab-driven rewiring of membrane transport. Furthermore, our recent work has uncovered multilayered and stage-specific reprogramming of Rab networks during infection, including Rab41-mediated membrane repair and RabGAP1L-Rab11A-dependent bacterial expulsion.
Streptococcus pyogenes infects the human pharynx, causing pharyngitis and tonsillitis, and as secondary complications, it can lead to acute glomerulonephritis and rheumatic fever. In recent years in Japan, there has been a trend of increasing cases of severe invasive streptococcal infections, which involve soft tissue necrosis, shock, and multiple organ failure. Streptococcus pneumoniae often resides in the nasal cavities of children, causing otitis media and pneumonia. In pneumonia among the elderly, it is frequently detected as a causative agent, and it has long been the case that more than half of the clinical isolates exhibit resistance to antibiotics. This overview discusses the responsible molecules and pathogenic mechanisms involved in these streptococcal infections.
Enterococci, particularly Enterococcus faecium, are major opportunistic pathogens, and the spread of multidrug-resistant strains, especially vancomycin-resistant enterococci (VRE), is a serious public health concern. Conjugative plasmids are key drivers of antimicrobial resistance gene (ARG) dissemination in enterococci. Until recently, all such plasmids were assumed to be circular. Here, we summarize our studies on pELF-type linear plasmids, a novel family of enterococcal plasmids.We first identified pELF1, a linear plasmid that carries both VanA- and VanM-type vancomycin resistance gene clusters and characterized its hybrid terminal structure and its ability to cross species barriers within the genus Enterococcus, thereby disseminating ARGs. In a documented episode of nosocomial VRE transmission, we then showed that a pELF-type linear plasmid (pELF2) mediated interspecies transfer of vancomycin resistance gene clusters among E. faecium, E. raffinosus, and E. casseliflavus.Using integrated molecular epidemiological, phenotypic, and transcriptomic analyses, we demonstrated that pELF-type linear plasmids are globally distributed as multiple lineages that retain a conserved backbone while adapting to their E. faecium hosts, functioning as major vehicles for ARGs in E. faecium. More recently, we showed that pELF-type linear plasmids have evolved through the acquisition of transposons and a circular plasmid carrying linezolid resistance genes, leading to strains with concomitant resistance to vancomycin and linezolid in both clinical and environmental settings.These findings indicate that pELF-type linear plasmids play a crucial role in the development of multidrug resistance in E. faecium and underscore the importance of incorporating this plasmid family into surveillance and intervention strategies aimed at limiting antimicrobial resistance.
Heterocyclic triazines and their derivatives have excellent biological activity and have been used as herbicides and anticancer drugs. A large number of derivatives were synthesized and their biological activity was investigated. Some bacteria synthesize the triazine derivatives such as Nostocine A, Toxoflavin, and Fluviol from GTP using enzymes similar to those in the synthesis pathway of Riboflavin (vitamin B2). These triazine derivatives show antibiotic activity. In particular, research on Toxoflavin has progressed as a toxin produced by bacteria that cause seedling rot and rice grain blight in rice. It has recently been revealed that Fluviol, which is produced by bacteria, acts to suppress the growth of pathogenic bacteria. This review will focus on triazine derivatives produced by bacteria.
Enterohemorrhagic Escherichia coli (EHEC) is an important pathogen since more than 3,000 cases have been reported annually in Japan. With the advent of next-generation sequencing, it has become feasible to analyze numerous strains using whole-genome sequence (WGS) analysis, making its application to surveillance a realistic possibility. In this paper, we introduce the following research outcomes achieved by our group utilizing WGS analysis of EHEC: 1) development of a WGS analysis pipeline to enhance the accuracy of the surveillance, 2) investigation of the dynamics of mobile elements such as plasmids and phages, and 3) analysis of the phylogeny and pathogenicity of newly identified highly pathogenic EHEC strains.
