Aug 2026· Biology· Vol 15, pp. 1338· 0 citations· 76 references
Medicine
TL;DR
Findings reveal that this enzyme plays a critical role in controlling bacterial disease-causing ability through its effects on cellular metabolism, and shows promise as a safe and effective vaccine candidate to protect farmed fish against Edwardsiella infections.
Abstract
Simple Summary Edwardsiella tarda is a bacterium that causes severe disease in fish, leading to major economic losses for aquaculture worldwide. Understanding how this bacterium causes infection is essential for developing effective prevention strategies. In this study, we investigated a key bacterial enzyme called phosphoenolpyruvate carboxykinase (PEPCK), which helps control the bacterium’s energy metabolism. When we removed the gene responsible for producing this enzyme, the bacteria became less harmful to fish, grew faster, and showed increased movement. Importantly, this modified bacterium triggered a strong immune response in fish and protected them against subsequent infection with the deadly form of the bacteria. Fish that received the modified bacteria survived at much higher rates compared to unprotected fish. These findings reveal that this enzyme plays a critical role in controlling bacterial disease-causing ability through its effects on cellular metabolism. The modified bacteria show promise as a safe and effective vaccine candidate to protect farmed fish against Edwardsiella infections, potentially reducing disease outbreaks and economic losses in aquaculture while decreasing the need for antibiotic treatments.
Pseudomonas plecoglossicida is a major etiological agent of visceral white-spot disease in diverse aquaculture species. Chorismate synthase (AroC), a key enzyme in the aromatic amino acid biosynthetic pathway, is essential for central metabolism and has been implicated in bacterial virulence. In this study, an aroC deletion mutant (ΔaroC) and a complemented strain (CΔaroC) were constructed to investigate the role of AroC in virulence regulation and to evaluate its potential as a live-attenuated vaccine candidate. Compared with the wild-type (WT) strain, ΔaroC exhibited significantly reduced growth, motility, hemolytic activity, and biofilm formation. In infection experiments, ΔaroC showed markedly attenuated virulence, resulting in 90% host survival. In a goldfish vaccination-challenge model, immunization with ΔaroC conferred moderate protective efficacy, with a relative percent survival (RPS) of 62%. Transcriptomic analysis revealed that aroC deletion led to the downregulation of genes involved in amino acid metabolism, ABC transporters, and quorum sensing pathways. These results suggest that AroC contributes to pathogenicity by coordinating metabolic processes and environmental adaptation. Together, our findings identify AroC as an important virulence determinant in P. plecoglossicida and suggest that ΔaroC is a promising live-attenuated vaccine candidate that warrants further validation in the natural host.
Yingchao Wang, Ping Shao, Zhijuan Mao et al.· Microbial Pathogenesis· 0 citations
Simple Summary Bacterial diseases are a major challenge in aquaculture, creating an urgent need for new disease-control strategies. In this study, we investigated the role of a natural immune protein, CXCL14, from grass carp in protecting fish against bacterial infections. We found that this protein was highly expressed in immune-related tissues and was upregulated after bacterial challenge. Recombinant CXCL14 showed broad-spectrum antibacterial activity against several important fish pathogens and protected grass carp by reducing bacterial burdens and improving survival after infection. Laboratory experiments also showed that the protein disrupted bacterial membranes and interacted with purified bacterial DNA in vitro. These findings improve our understanding of the antibacterial function of fish CXCL14 and provide a basis for future studies on its potential application in aquaculture.
Yang Hu, Yu Chen, Weicheng Wang et al.· Animals· 0 citations
Spodoptera frugiperda (fall armyworm) is a globally distributed and highly destructive migratory pest, while Serratia marcescens is a widespread entomopathogenic bacterium capable of infecting diverse insects. In this study, oral infection with S. marcescens strain SM001 exhibited potent virulence, with an LC50 of 7.40 × 106 CFU/mL at 168 h post-infection (hpi). Logistic regression modeling demonstrated that the bacterium enters an exponential proliferation phase within the hemolymph approximately 48-54 h after infection. Infection significantly upregulated Duox and Nos, induced severe oxidative stress, and activated an apoptotic cascade involving Cyt c, p53, and caspase, culminating in extensive midgut epithelial cell apoptosis. Mitigating oxidative stress via targeted Vitamin C supplementation or Duox knockdown alleviated midgut tissue damage and delayed bacterial dissemination. However, exogenous Vitamin C treatment decreased larval mortality, whereas Duox knockdown failed to improve overall survival, revealing a critical physiological trade-off between ROS-mediated pathogen clearance and host immunopathology. Overall, SM001 disrupts midgut redox homeostasis, drives excessive H2O2 accumulation, and breaches the intestinal barrier to facilitate hemocoel translocation, ultimately leading to lethal systemic septicemia. These findings highlight the pivotal role of host-mediated immunopathology in bacterial pathogenesis and provide a robust theoretical foundation for developing advanced microbial control strategies against S. frugiperda.
Simple Summary Aeromonas salmonicida causes severe mortality in grouper and other farmed fish, resulting in considerable economic losses in aquaculture. Although the trpE gene participates in tryptophan biosynthesis, its role in bacterial virulence remains unclear. Here, we investigated the function of trpE in A. salmonicida SRW-OG1. Deletion of trpE impaired bacterial growth, flagella formation and multiple virulence traits. In vivo assays confirmed that mutant exhibite attenuated virulence, and reduced tissue colonization, offering effective immune protection against wild-type infection. Omics analyses revealed that trpE modulates bacterial pathogenicity via quorum sensing and motility pathways, supporting its potential as a live attenuated vaccine candidate.
Bdellovibrio bacteriovorus represents one of nature's most remarkable examples of obligate bacterial predation. This small, highly motile bacterium exhibits a biphasic life cycle alternating between a free-swimming attack phase and an intraperiplasmic growth phase within gram-negative prey bacteria. Recent advances have elucidated the molecular machinery coordinating prey recognition, invasion, and host manipulation, revealing sophisticated enzymatic arsenals and regulatory networks that orchestrate the predatory program. Transcriptomic studies demonstrate precise temporal control of lytic enzymes, nutrient acquisition systems, and developmental checkpoints throughout the life cycle. Bdellovibrio and related organisms occupy diverse niches, including soil, freshwater, and the mammalian gut, where they influence bacterial community composition through top-down predation. This ecological ubiquity, combined with inherent bactericidal activity, has generated considerable interest in therapeutic applications against multidrug-resistant pathogens, with encouraging results in animal infection models. In this article, we synthesize current understanding of predatory mechanisms, environmental roles, and biotechnological potential of Bdellovibrio while identifying key knowledge gaps: the regulatory logic governing life cycle transitions, molecular determinants of host range, and predator-prey population dynamics. Addressing these questions will advance both fundamental microbiology and antimicrobial innovation.
Sampriti Mukherjee, A. Lovering· Annual Review of Microbiolog...· 0 citations
Clostridioides difficile is a major cause of antibiotic-associated diarrhea and a significant public health threat. During its infectious cycle, C. difficile encounters various stresses within the gastrointestinal tract. Clp proteases play a crucial role in bacterial stress responses and protein homeostasis. In this study, we investigated the role of the Clp ATPase, ClpC, in C. difficile physiology using genetic, phenotypic, and proteomic analyses. Deletion of clpC reduced heat shock survival but did not affect growth or stationary phase survival under non-stress conditions. Comparative proteomics revealed that ClpC influences the abundance of proteins involved in sporulation, motility, metabolism, and cell wall biosynthesis. The ΔclpC mutant exhibited faster sporulation and increased motility compared to the parental strain. Peptidoglycan quantification showed a significant increase in the ΔclpC mutant, suggesting ClpC's involvement in cell wall homeostasis. The mutant also displayed altered sensitivity to cell wall-targeting antibiotics. Unlike in other bacteria, ClpC did not control the level of MurA, a key enzyme in peptidoglycan precursor synthesis. Instead, the SEDS protein RodA, a transglycosylase involved in peptidoglycan polymerization, accumulated in the ΔclpC mutant. Our findings highlight the pleiotropic role of ClpC in C. difficile, particularly in sporulation, motility, and cell wall metabolism, likely through the degradation of key proteins. Understanding the molecular mechanisms of ClpC-mediated proteolysis in C. difficile stress responses and virulence may provide insights for the development of novel strategies to combat this important pathogen.
Pierre Lacotte, Aurélie Lotoux, Kimberley Casado et al.· Microbial Pathogenesis· 0 citations