Synergistic Activity of Cyclo(phe-pro) Antibiotic from Streptomyces violascens VS in Reducing the Drug Resistance Burden of Clinically Significant Pathogens

Abstract A potential novel antibiotic-producing soil Streptomyces violascens VS was isolated and confirmed through 16S rDNA sequencing. A novel antibiotic from S. violascens VS was extracted from the mass-cultured broth through organic solvents using chloroform: methanol by column and thin layer chromatography. Among the ten fractions, collected from elution by 9:3, 1:1, and 7:3 chloroform: methanol mixtures, the` 3rd fraction (after 3 minutes) of the 7:3 mixture showed maximum bactericidal activity against P. aeruginosa, E. coli, Bacillus sp., K. pneumoniae, and Proteus sp., with zones of inhibition of 18, 12, 19, 18, and 14 mm respectively. The equivalent fraction yielded 2.3 g/l of pure antibiotic. In the GC-MS spectrum the active compound identified as Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro-3-(phenylmethyl), or Cyclo(phe-pro). The antibiotic’s fractional inhibitory concentration index (FICI) showed synergistic and partially synergistic activity with ten different commercial antibiotics such as ampicillin, sulfamethoxazole, erythromycin, amoxicillin, azithromycin, ofloxacin, levofloxacin, cefadroxil, cefixime, and ciprofloxacin against Gram-positive and Gram-negative bacteria, especially with cell wall synthesis inhibiting antibiotics. Thus, the synergistic usage of Cyclo(phe-pro) peptide antibiotic with commercial antibiotics recognized to have potential broad spectrum activity and possibility to control infections caused by MDR strains. GRAPHICAL ABSTRACT