Longistylin A from Cajanus cajan (L.) Millsp. disturbs glycerophospholipid metabolism and cytokinin biosynthesis of Nocardia seriolae

Nocardia genus members are characterized as Gram-positive, non-motile, and aerobic actinomycetes, belonging to the Actinobacteria class within the Corynebacteriales order (Rita M. Traxler et al., 2022; Wilson, 2012). This genus encompasses over 100 acknowledged species, widely distributed across aquatic and terrestrial habitats. Numerous species within this genus are recognized as the cause of nocardiosis in both humans and various animal species, leading to diverse clinical ailments and substantial mortality (Barry et al., 2022; Margalit et al., 2021). Nocardiosis poses challenges in treatment, relying predominantly on a limited array of antibiotics and requiring months or years of antibacterial treatment (Besteiro et al., 2023; Hershko et al., 2023). No standard treatment for nocardiosis has been established due to limited reporting on the effectiveness of new drugs, treatment failures and drug resistance (Gnanagobal and Santander, 2022; Hoang et al., 2020; Maekawa et al., 2018).

Within aquatic environments, four species of Nocardia (N. asteroides, N. seriolae, N. salmonicida, and N. crassostreae) have also been identified in diseased aquatic organisms (Maekawa et al., 2018). Recently, N. seriolae has emerged as the predominant fish nocardiosis pathogen, inducing various symptoms such as skin ulcers, abdominal swelling, and distinct white nodules in fish gills, as well as organs like liver, heart, spleen, and kidney (Gnanagobal and Santander, 2022; Guo et al., 2022; Teng et al., 2022). The incidence of N. seriolae infections is increasing among various fish species, with the economically valuable largemouth bass being particularly affected, leading to significant economic losses in the aquaculture industry (Hoang et al., 2020; Huang et al., 2021; Jiang et al., 2022; Lei et al., 2020)

Cytokinin is commonly considered a plant hormone, believed to be produced by plants and used in agriculture as a growth promoter (Jameson, 2023). Recent studies have discovered that certain bacteria can also produce cytokinin (Dabravolski and Isayenkov, 2021; Kabbara et al., 2020). Mycobacterium tuberculosis produces cytokinin as a signaling molecule for inter-bacterial communication, aiding in host infection (Samanovic et al., 2015). Nocardia infection can often be mistaken for tuberculosis (Nakagoshi et al., 2022; Pan et al., 2021). However, there is little evidence about whether Nocardia can also produce cytokinin (Ghodhbane-Gtari et al., 2019), leaving a void in understanding both the benefits and the regulatory pathways involved in cytokinin production by Nocardia.

Cajanus cajan (L.) Millsp, commonly known as pigeon pea, ranks as the sixth-largest edible bean globally (Cai et al., 2015; Schuster et al., 2016). It is primarily distributed in South and Southeast Asia, notably in countries like India, Myanmar, and China (Zhao et al., 2023). In traditional Chinese medicine, the leaves of C. cajan are employed to treat wounds, malaria, coughs, and abdominal pain (Pal et al., 2011). Analysis of its chemical composition highlights the presence of stilbenes and flavonoids as its primary constituents in pharmacology (Chen et al., 2023). Among the distinct stilbene compounds found in C. cajan, longistylin A (LGA) has demonstrated antibacterial properties against methicillin-resistant Staphylococcus aureus (Wu et al., 2020). However, the mechanisms of action for LGA remain poorly understood.

In this study, we explored the effect of C. cajan extract (CJE) and LGA against N. seriolae and substantial antibacterial mechanisms based on antimicrobial analysis and multi-omics data.

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