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.
Highlights
Streptococcus parauberis is one of the major pathogenic bacteria which cause economic losses in the aquaculture industry in the Northeast Asia fish farming industry, including Korea
In freshwater and marine cultures, it was first found in Scophthalmus maximus and is the leading cause of chronic streptococcal infection, but it was initially included in the S. uberis subtypes [1, 2]
In S. parauberis, 112 nonhomologous proteins were identified as essential when its nonhomologous proteins were aligned with the essential protein sequences of five different streptococcal species named as Streptococcus agalactiae A909, Streptococcus pneumoniae, Streptococcus pyogenes MGAS5448, Streptococcus pyogenes NZ131, and Streptococcus sanguinis
Summary
Streptococcus parauberis is one of the major pathogenic bacteria which cause economic losses in the aquaculture industry in the Northeast Asia fish farming industry, including Korea. In freshwater and marine cultures, it was first found in Scophthalmus maximus (turbot) and is the leading cause of chronic streptococcal infection, but it was initially included in the S. uberis subtypes [1, 2]. With a progressively developing aquaculture industry, bacterial pathogen infections have increased, causing exponential losses of different fish species based on their geographical regions like Paralichthys olivaceus (olive flounder) in South Korea and Japan, Scophthalmus maximus (turbot) in Spain, Sebastes ventricosus (sea bass species) in Japan, and Morone saxatilis (striped bass) in North America due to streptococcosis. It produces a considerable deficit economically to International Journal of Genomics fish farmers because of its substantial impact on fish stock mortality, and its occurrence must be controlled [6, 8]
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