Pharmacodynamics of Ceftiofur Selected by Genomic and Proteomic Approaches of Streptococcus parauberis Isolated from the Flounder, Paralichthys olivaceus

Abstract

We employed an integrative strategy to present subtractive and comparative metabolic and genomic-based findings of therapeutic targets against Streptococcus parauberis. For the first time, we not only identified potential targets based on genomic and proteomic database analyses but also recommend a new antimicrobial drug for the treatment of olive flounder (Paralichthys olivaceus) infected with S. parauberis. To do that, 102 total annotated metabolic pathways of this bacterial strain were extracted from computational comparative metabolic and genomic databases. Six druggable proteins were identified from these metabolic pathways from the DrugBank database with their respective genes as mtnN, penA, pbp2, murB, murA, coaA, and fni out of 112 essential nonhomologous proteins. Among these hits, 26 transmembrane proteins and 77 cytoplasmic proteins were extracted as potential vaccines and drug targets, respectively. From the FDA DrugBank, ceftiofur was selected to prevent antibiotic resistance as it inhibited our selected identified target. Florfenicol is used for treatment of S. parauberis infection in flounder and was chosen as a comparator drug. All tested strains of fish isolates with S. parauberis were susceptible to ceftiofur and florfenicol with minimum inhibitory concentrations (MIC) of 0.0039–1 μg/mL and 0.5–8 μg/mL, IC50 of 0.001–0.5 μg/mL and 0.7–2.7 μg/mL, and minimum biofilm eradication concentrations (MBEC) of 2–256 μg/mL and 4–64 μg/mL, respectively. Similar susceptibility profiles for ceftiofur and florfenicol were found, with ceftiofur observed as an effective and potent antimicrobial drug against both planktonic and biofilm-forming strains of the fish pathogen Streptococcus parauberis, and it can be applied in the aquaculture industry. Thus, our predictive approach not only showed novel therapeutic agents but also indicated that marketed drugs should also be tested for efficacy against newly identified targets of this important fish pathogen.