Multi-omics reveals the increased biofilm formation of Salmonella Typhimurium M3 by the induction of tetracycline at sub-inhibitory concentrations

Exposure to sub-inhibitory concentrations (sub-MICs) of antibiotics could induce the biofilm formation of microorganisms, but its underlying mechanisms still remain elusive. In the present work, biofilm formation by Salmonella Typhimurium M3 was increased when in the presence of tetracycline at sub-MIC, and the highest induction was observed with tetracycline at 1/8 MIC. The integration of RNA-sequencing and untargeted metabolomics was applied in order to further decipher the potential mechanisms for this observation. In total, 439 genes and 144 metabolites of S. Typhimurium M3 were significantly expressed after its exposure to 1/8 MIC of tetracycline. In addition, the co-expression analysis revealed that 6 genes and 8 metabolites play a key role in response to 1/8 MIC of tetracycline. The differential genes and metabolites were represented in 12 KEGG pathways, including five pathways of amino acid metabolism (beta-alanine metabolism, tryptophan metabolism, arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glutathione metabolism), three lipid metabolism pathways (biosynthesis of unsaturated fatty acids, fatty acid degradation, and fatty acid biosynthesis), two nucleotide metabolism pathways (purine metabolism, and pyrimidine metabolism), pantothenate and CoA biosynthesis, and ABC transporters. Metabolites (anthranilate, indole, and putrescine) from amino acid metabolism may act as signaling molecules to promote the biofilm formation of S. Typhimurium M3. The results of this work highlight the importance of low antimicrobial concentrations on foodborne pathogens of environmental origin.

Automated summary

Exposure to sub-inhibitory concentrations of antibiotics can induce biofilm formation in microorganisms, but the underlying mechanisms are still unclear. This study used RNA-sequencing and untargeted metabolomics to investigate the potential mechanisms of tetracycline-induced biofilm formation in Salmonella Typhimurium M3. The results showed that tetracycline at 1/8 MIC significantly increased biofilm formation, and key pathways involved amino acid metabolism, lipid metabolism, nucleotide metabolism, pantothenate and CoA biosynthesis, and ABC transporters. This study highlights the importance of low antimicrobial concentrations on foodborne pathogens.