Transcriptomic and metabolomic insights from functionalized V-shaped Lactiplantibacillus plantarum towards mitigating Candida albicans virulence.

The genomic capacity of probiotic Lactobacilli enables producing bioactive metabolites that represent promising alternatives to antibiotics for combating food-borne and multi drug-resistant pathogens. The current study characterizes a global antagonistic potential of the probiotic bacterium Lactiplantibacillus plantarum, which demonstrates unique multicellular structuring triggered in response to acidic environments. We demonstrate the inhibitory potential of postbiotics derived from the V-shaped structured L. plantarum (VSLP) against Candida albicans. Using the liquid chromatography-mass spectrometry (LC-MS) profiling, we further identify different antibiofilm metabolites secreted during the VSLP formation. Transcriptomic studies reveal a notable upregulation of genes associated with the biosynthesis of aromatic amino acids such as serD, ywqE2, trpB, trpA. Furthermore, significant differential expressions were observed in genes within the biosynthetic gene cluster (BGCs) identified through antiSMASH analysis of L. plantarum genome. In addition, two novel VSLP metabolites (bluensomycin and majoroside F6) functioned as inhibitors of Ras-adenylate cyclase pathway that control biofilms and hyphae in yeast. We suggest that functionalized probiotic cells, such as VSLP, may effectively control the pathogenic microorganisms that provide a staple basis for developing future therapeutic probiotics.