Bacteria release membrane vesicles (MVs) that play important roles in various biological processes. However, the mechanisms of MV formation in Gram-positive bacteria are unclear, as these cells possess a single cytoplasmic membrane that is surrounded by a thick cell wall. Here we use live cell imaging and electron cryo-tomography to describe a mechanism for MV formation in Bacillus subtilis. We show that the expression of a prophage-encoded endolysin in a sub-population of cells generates holes in the peptidoglycan cell wall. Through these openings, cytoplasmic membrane material protrudes into the extracellular space and is released as MVs. Due to the loss of membrane integrity, the induced cells eventually die. The vesicle-producing cells induce MV formation in neighboring cells by the enzymatic action of the released endolysin. Our results support the idea that endolysins may be important for MV formation in bacteria, and this mechanism may potentially be useful for the production of MVs for applications in biomedicine and nanotechnology.
The expression of hepatocyte growth factor (HGF) and its receptor, c-Met, was investigated immunohistologically in tissue specimens of patients with a pulmonary adenocarcinoma. The prognosis was significantly worse in the HGF-positive or c-Met-positive patients than in the negative patients. Multivariate analysis showed that c-Met had a significant effect on the prognosis, whereas HGF did not. Our findings suggest that HGF and c-Met play an important role in tumor progression and that c-Met can be a useful prognostic marker for pulmonary adenocarcinomas.
Leiomyomatosis peritonealis disseminata (LPD) is a rare clinicopathological entity typically observed in women of reproductive age. We report a case of LPD with malignant change in a man. A 77‐year‐old man presented with a mass measuring 10 cm in diameter at the terminal ileum and numerous peritoneal small nodules that were revealed by abdominal computed tomography. Right hemicolectomy with lymph node dissection was performed. Macroscopically, a tumor of the terminal ileum consisted of aggregates of small nodular lesions with calcification and necrosis. The wall of the ileum and colon was intact. Microscopically, some of the nodular lesions consisted of neoplastic growths of atypical spindle cells with cellular atypism and abnormal mitoses. A few of these lesions were completely surrounded by smooth muscle bundles. Hemorrhages and necroses were found within the tumor nodules. Immunohistochemically, the tumor cells were positive for vimentin, desmin, muscle actin, α‐smooth muscle actin, cytokeratin and p53. The remaining nodular lesions, including small peritoneal lesions, were composed of hypocellular hyalinizing nodules. This case was thought to be LPD with malignant change, although the pathogenesis was uncertain because the tumor cells were negative for estrogen and progesterone receptors.
The capture of antimicrobial resistance genes (ARGs) by mobile genetic elements (MGEs) plays a critical role in resistance acquisition for human-associated bacteria. Although aquaculture environments are recognized as important reservoirs of ARGs, intra- and intercellular mobility of MGEs discovered in marine organisms is poorly characterized. Here, we show a new pattern of interspecies ARGs transfer involving a ‘non-conjugative’ integrative element. To identify active MGEs in a Vibrio ponticus isolate, we conducted whole-genome sequencing of a transconjugant obtained by mating between Escherichia coli and Vibrio ponticus. This revealed integration of a plasmid (designated pSEA1) into the chromosome, consisting of a self-transmissible plasmid backbone of the MOBH group, ARGs, and a 13.8-kb integrative element Tn6283. Molecular genetics analysis suggested a two-step gene transfer model. First, Tn6283 integrates into the recipient chromosome during suicidal plasmid transfer, followed by homologous recombination between the Tn6283 copy in the chromosome and that in the newly transferred pSEA1. Tn6283 is unusual among integrative elements in that it apparently does not encode transfer function and its excision barely generates unoccupied donor sites. Thus, its movement is analogous to the transposition of insertion sequences rather than to that of canonical integrative and conjugative elements. Overall, this study reveals the presence of a previously unrecognized type of MGE in a marine organism, highlighting diversity in the mode of interspecies gene transfer.
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