A genomic investigation of Lactic Acid Bacteria-derived biosynthetic gene clusters reveals therapeutic potential of a novel Lactobacillus species

Background: Amidst the escalating challenges of gut dysbiosis and antibiotic resistance, the exigency for research on 1) beneficial microbes to help positively shape the gut microbiome, and 2) alternative antimicrobials to combat bacterial pathogens, has reached critical levels. Lactic Acid Bacteria (LAB), celebrated for their prolific probiotic potential, offer a solution to both of these problems. Generally recognized as safe (GRAS), a status issued by the U.S. Food and Drug Administration, LAB are currently permitted for use in the food industry as biopreservatives and live probiotics, in agriculture as feedstock and alternatives to chemical pesticides, and in pharmaceutical applications for antimicrobial properties, production of bioactive compounds, and their role in drug delivery systems.

Methods: By employing a culturomics approach in conjunction with advanced anaerobic techniques, we have isolated a novel species belonging to the genus Lactobacillus, with 97.5% similarity to its nearest phylogenetic neighbor (new species cutoff value is < 98.3% nucleotide similarity based on 16S rRNA gene sequencing). In silico analysis of the whole genome has revealed a number of biosynthetic gene clusters implicated in probiotic traits, suggesting our full phenotypic characterization will yield many avenues for commercialization.

Results: Genomic mining of this nascent species has brought to light several compelling areas of interest, particularly with respect to bacteriocin production. Genes homologous to core structural proteins of known antimicrobials were found using computational programs such as BAGEL4 and antiSMASH, suggesting this isolate is capable of killing known human pathogens such as Clostridioides difficile and Staphylococcus aureus. Current literature also suggests that closely related members of this clade exhibit anti-inflammatory, immunomodulatory, and intestinal barrier protection in animal and human models, thus warranting further investigation into this isolate’s versatility in healthcare applications.

Conclusions: Owing to the promising outcomes from preliminary in silico work, a more comprehensive investigation into this novel species will be performed to characterize its full antimicrobial spectrum and expose the transformative innovations it harbors.