The mechanisms of lead resistance in Lactiplantibacillus plantarum: Insights from proteomics and metabolomics analyses

Abstract

Lead (Pb), a toxic heavy metal prevalent in the environment, poses serious health risks due to its persistence and bioaccumulation. While certain Lactiplantibacillus plantarum strains have demonstrated the ability to mitigate Pb toxicity in vivo, the molecular mechanisms remain unclear. We hypothesized that Pb-resistant L. plantarum strains employ unique physiological adaptations to survive and counteract Pb stress. To test this, tandem mass tag (TMT) proteomics and LC-MS metabolomics were applied to compare the Pb-tolerant strain CCFM8661 and Pb-sensitive strain CCFM578 under 128 mg/L Pb exposure. Metabolomics revealed that Pb stress altered levels of key metabolites, including proline, arginine, glutamic acid, and mannitol. Proteomics showed that Pb stress decreased the abundance of 30 key proteins, such as 1-phosphofructokinase, pyruvate kinase, and β-galactosidase, while increasing 10 key proteins, including thioredoxin, GTP pyrophosphokinase, and tRNA-binding protein. Integration of metabolomics and proteomics data indicated that Pb stress disrupted amino acid metabolism, suppressed energy pathways, and upregulated nucleic acid repair mechanisms. Notably, the Pb-resistant strain CCFM8661 demonstrated strong antioxidant defenses and could cope with Pb stress through ABC transporters, low-energy metabolism, membrane modification, and osmotic regulation. In contrast, CCFM578 exhibited inhibited transport activity, compromised DNA repair, and disrupted energy metabolism. Our findings suggest that L. plantarum's Pb resistance relies on coordinated regulation of antioxidant systems, amino acid/osmolyte synthesis, and transporter activity, along with adaptive energy conservation. This study offers valuable insights into microbial Pb detoxification strategies.