Photodynamic therapy (PDT) is a known strategy for treating cancer; in PDT, photosensitizers are activated by light stimulation and then induce reactive oxygen species (ROS) production to damage cancer tissues. Recently evidence has shown that PDT can also be used as a novel treatment strategy to control pathogenic bacteria. In previous studies, the photosensitizer DH-I-180-3 was reported to effectively regulate multidrug-resistant Mycobacterium tuberculosis growth. Here, we confirmed the effects of DH-I-180-3 on the antibacterial activity and inflammatory response of macrophages to Salmonella. Photoactivated DH-I-180-3 regulated intracellular bacterial growth in Salmonella-infected macrophages. Moreover, DH-I-180-3 increased intracellular ROS levels in Salmonella-infected macrophages. The phosphorylation of the intracellular signaling proteins IκBα and JNK1/2 was increased in DH-I-180-3-treated Salmonella-infected macrophages. Additionally, we observed that DH-I-180-3 significantly increased the mRNA expression and protein secretion of the proinflammatory cytokine TNF-α and promoted phagosome maturation by upregulating EEA1, LAMP1, and Cathepsin D in Salmonella-infected macrophages. Overall, these results demonstrate that photoactivated DH-I-180-3 enhances the bactericidal response to intracellular bacterial infection by promoting inflammatory signaling pathways and phagosome maturation. Therefore, DH-I-180-3 has the potential to be developed into PDT for treating bacterial-infection.
A well-conserved LAMMER kinase in yeast and filamentous fungi, is a dual-specificity kinase with multiple roles in fungal biology. In this study, we assessed the roles of LkhA in Aspergillus flavus, a toxigenic fungus that produces aflatoxin B1. lkhA deletion mutants exhibited defects in fungal growth, conidiophore development, and sclerotia formation. These mutants exhibited impaired tolerance to oxidative and cell wall stresses. Moreover, the absence of lkhA resulted in a decrease in aflatoxin B1 production. The kernel assay revealed that the lkhA deletion mutants exhibited reduced production of conidia and aflatoxin B1, implying that LkhA can affect fungal toxigenesis and pathogenicity. Taken together, these results demonstrate that LkhA is important for differentiation, mycotoxin production, and pathogenicity in A. flavus.
The escalating antibiotic resistance crisis poses a significant challenge to global public health, threatening the efficacy of current treatments and driving the emergence of multidrug-resistant pathogens. Among the various factors associated with bacterial antibiotic resistance, small regulatory RNAs (sRNAs) have emerged as pivotal post-transcriptional regulators which orchestrate bacterial adaptation to antibiotic pressure via diverse mechanisms. This review consolidates the current knowledge on sRNA-mediated mechanisms, focusing on drug uptake, drug efflux systems, lipopolysaccharides, cell wall modification, biofilm formation, and mutagenesis. Recent advances in transcriptomics and functional analyses have revealed novel sRNAs and their regulatory networks, expanding our understanding of resistance mechanisms. These findings highlight the potential of targeting sRNA-mediated pathways as an innovative therapeutic strategy to combat antibiotic resistance, and offer promising avenues for managing challenging bacterial infections.
This review explores current advancements in microbiome functional analysis enabled by next-generation sequencing technologies, which have transformed our understanding of microbial communities from mere taxonomic composition to their functional potential. We examine approaches that move beyond species identification to characterize microbial activities, interactions, and their roles in host health and disease. Genome-scale metabolic models allow for in-depth simulations of metabolic networks, enabling researchers to predict microbial metabolism, growth, and interspecies interactions in diverse environments. Additionally, computational methods for predicting metabolite profiles offer indirect insights into microbial metabolic outputs, which is crucial for identifying biomarkers and potential therapeutic targets. Functional pathway analysis tools further reveal microbial contributions to metabolic pathways, highlighting alterations in response to environmental changes and disease states. Together, these methods offer a powerful framework for understanding the complex metabolic interactions within microbial communities and their impact on host physiology. While significant progress has been made, challenges remain in the accuracy of predictive models and the completeness of reference databases, which limit the applicability of these methods in under-characterized ecosystems. The integration of these computational tools with multi-omic data holds promise for personalized approaches in precision medicine, allowing for targeted interventions that modulate the microbiome to improve health outcomes. This review highlights recent advances in microbiome functional analysis, providing a roadmap for future research and translational applications in human health and environmental microbiology.
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