2023 FDA Science Forum
Concentration-dependent proteome response of a strong biofilm producer S. epidermidis RP62A to subinhibitory tigecycline
- Authors:
- Center:
-
Contributing OfficeNational Center for Toxicological Research
Abstract
Staphylococcus epidermidis is a leading cause of biofilm-associated infections on implanted medical devices. During the treatment of an infection, bacterial cells inside biofilms may be exposed to sublethal concentrations of the antimicrobial agents. In the present study, the effect of subinhibitory concentrations of tigecycline (TC) on biofilms formed by S. epidermidis strain RP62A was investigated using a quantitative global proteomic technique. Sublethal concentrations of TC [1/8 (T1) and 1/4 (T2) MIC] promoted biofilm production in strain RP62A, but 1/2 MIC TC (T3) significantly inhibited biofilm production. Overall, 413, 429, and 518 proteins were differentially expressed in biofilms grown with T1, T2, and T3 MIC of TC, respectively. As the TC concentration increased, the number of induced proteins in each Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway increased. Most upregulated proteins belonged to the metabolism pathway, suggesting that it may play an important role in the defense of strain RP62A biofilm cells against TC stress. Sub-MIC TC treatment of strain RP62A biofilms also led to significant changes of protein expression related to biofilm formation, antimicrobial resistance, virulence, quorum sensing, ABC transporters, protein export, ribosomes, and essential proteins. Interestingly, in addition to tetracycline resistance, proteins involved in resistance of various antibiotics, including aminoglycosides, β-lactams, erythromycin, fluoroquinolones, mupirocin, rifampicin and trimethoprim were differentially expressed. This study will greatly advance our understanding of antibiotic resistance mechanisms in treating pathogenic biofilms and combating disseminated biofilm infections.