Subinhibitory concentrations of amoxicillin, lincomycin, and oxytetracycline commonly used to treat swine increase Streptococcus suis biofilm formation

Authors: WAACK, URSULA - Orise Fellow; Nicholson, Tracy

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/23/2018
Publication Date: 11/6/2018
Citation: Waack, U., Nicholson, T.L. 2018. Subinhibitory concentrations of amoxicillin, lincomycin, and oxytetracycline commonly used to treat swine increase Streptococcus suis biofilm formation. Frontiers in Microbiology. 9:2707. https://doi.org/10.3389/fmicb.2018.02707.
DOI: https://doi.org/10.3389/fmicb.2018.02707

Interpretive Summary: Streptococcus suis is the leading bacterial pathogen effecting swine causing significant economic losses to the swine industry worldwide. S. suis contributes to a wide variety of clinical presentations in pigs ranging from asymptomatic carriage to lethal systemic disease. S. suis is also a zoonotic pathogen capable of causing invasive disease in humans. A barrier towards the development of improved vaccines or interventions for S. suis infections is a gap in our understanding of the factors contributing to persistence in the host, in which colonized pigs continue to shed and transmit S. suis. Routine management practices involve treating all pigs in the same pen or barn with appropriate antibiotics upon observing any pig exhibiting clinical signs associated with a bacterial infection. This study evaluated the effects of sub-minimal inhibitory concentrations (sub-MICs) of antibiotics commonly used by the swine industry on S. suis biofilms. Biofilms are adherent communities of bacteria that are protected from clearance mechanisms and are considered a key factor contributing to chronic or persistent bacterial infections. Our data demonstrate that sub-MICs of amoxicillin, lincomycin, and oxytetracycline increase overall biofilm formation under both static and flow conditions. These results indicate that exposure to sub-MICs of these commonly used antibiotics potentially contributes to increased persistence within the respiratory tract of swine, thereby increasing transmission dynamics among animals. Our data also demonstrate that sub-MICs of bacitracin, carbadox, chlortetracycline, enrofloxacin, gentamicin, neomycin, sulfadimethoxine, tiamulin, and tylosin did not increase S. suis biofilms. This data is critical for proper selection of antibiotics for successful treatment of swine bacterial diseases while minimizing potential collateral consequences.

Technical Abstract: Streptococcus suis is a bacterial swine pathogen with a significant economic burden. It typically colonizes the tonsil and nasal cavity of swine causing a variety of symptoms ranging from asymptomatic carriage to lethal systemic disease. A key barrier towards the development of improved vaccines or interventions for S. suis infections is a gap in our understanding of the mechanisms contributing to persistence in the host, in which colonized pigs continue to shed and transmit S. suis. We hypothesized that exposure to sub-MICs of antibiotics commonly used by the swine industry would increase the biofilm capacity of S. suis strains. Using a 96-well plate MIC protocol, we experimentally determined the MIC for each antibiotic for a virulent strain of S. suis strain that consistently formed biofilms using a standard crystal violet assay. Using this static biofilm assay, we demonstrate that sub-MICs of bacitracin, carbadox, chlortetracycline, enrofloxacin, gentamicin, neomycin, sulfadimethoxine, tiamulin, and tylosin did not increase S. suis biofilms. In contrast, we demonstrate that sub-MICs of amoxicillin, lincomycin, and oxytetracycline increase overall biofilm formation under both static and flow conditions. Collectively, our data demonstrate that exposure to sub-MICs of these commonly used antibiotics contributes to increased biofilm formation of S. suis, thereby potentially increasing survival and persistence within the respiratory tract of swine.