Evaluation of Sorghum Bioactive Compounds as Anti-bacterial Agents in Legionella and Listeria Infections

This research evaluated the antimicrobial potential of high-polyphenol extracts (HPE) from Sorghum bicolor against the intracellular bacterial pathogen Legionella pneumophila. Motivated by prior demonstrations that plant-derived polyphenols such as tea catechins (notably epigallocatechin gallate, EGCg) can restrict L. pneumophila replication in macrophages through enhanced inflammatory responses, the investigators tested whether sorghum polyphenols possess similar activity. Sorghum is a resilient cereal crop adapted to arid climates and has documented antioxidant and anticancer properties, but its antimicrobial effects had not been characterized. Using the RAW 264.7 mouse macrophage model and established L. pneumophila strains (including Philadelphia-1 SRS43 wild-type, ∆flaA and dotA::Tn), the team treated infected macrophages with sorghum high-polyphenol extract and monitored bacterial replication, macrophage viability, and cytokine secretion.

The study found that sorghum HPE attenuated L. pneumophila intracellular replication in a dose-dependent manner. Importantly, this restriction was not due to direct antimicrobial effects against L. pneumophila in rich media nor to increased host cell death: HPE did not impair bacterial growth in vitro nor compromise macrophage viability. Instead, HPE treatment enhanced secretion of pro-inflammatory cytokines, specifically tumor necrosis factor (TNF) and interleukin-6 (IL-6), from L. pneumophila infected macrophages. These findings mirror prior observations with tea polyphenols, where EGCg-mediated restriction of L. pneumophila was attributed to elevated macrophage inflammatory responses rather than direct bacterial killing. The data therefore support a model in which sorghum polyphenols potentiate innate immune mechanisms in macrophages, enhancing cytokine-driven restriction of intracellular replication. The work details methodological approaches including culture of L. pneumophila on supplemented ACES-buffered yeast extract and infection assays in RAW 264.7 macrophages, situating the experimental results within established Legionella pathogenesis frameworks, where intracellular replication depends on the Dot/Icm type IV secretion system to remodel host vacuoles and evade host defenses. Because L. pneumophila, an accidental human pathogen, is highly susceptible to mammalian innate immunity, interventions that amplify macrophage inflammatory responses represent a plausible strategy to limit intracellular replication.

The study's results suggest sorghum HPE are worthy of further exploration as potential antimicrobial agents or adjunctive therapeutics that act by modulating host responses. By revealing commonalities between plant polyphenol mediated antimicrobial activity across different botanical sources, this work lays a foundation for more detailed mechanistic studies, dose optimization, identification of active polyphenolic constituents, and exploration of effectiveness in additional cellular or in vivo models. Given sorghum's sustainability and adaptation to warming climates, these findings additionally highlight the potential for leveraging agroecological resources in developing novel bioactive compounds for infectious disease control.