Efficient Killing of Planktonic and Biofilm Embedded Coagulase-Negative Staphylococci by Bactericidal Protein P128 [PublishAheadOfPrint]

Coagulase negative staphylococci (CoNS) are the major causative agents of foreign body-related infections including catheters-related blood stream infections. Because of involvement of biofilms, the foreign body–related infections are difficult to treat. P128, a chimeric recombinant phage-derived ectolysin has been shown to possess bactericidal activity on strains of S. aureus including MRSA. We have now tested the killing potential of P128 on three clinically significant species of CoNS, S. epidermidis, S. haemolyticus and S. lugdunensis under a variety of physiological conditions representing growing and non-growing states. The MIC₉₀ and MBC₉₀ of P128 on 62 clinical strains of CoNS was found to be 16 and 32 μg/ml (0.58 and 1.16 μM) respectively demonstrating the bactericidal nature of P128 on CoNS strains. Serum showed a potentiating effect on P128 inhibition as indicated by 4-32 fold lower MIC values observed in serum. P128 caused rapid loss of viability in all the CoNS strains tested. Persisters of CoNS enriched in the presence of vancomycin or daptomycin were killed by P128 at 1X MIC in a rapid manner. Low concentrations of P128 caused a 2-5 log CFU reduction in stationary phase or poorly metabolizing CoNS cultures. P128 at low concentrations could eliminate CoNS biofilms in microtitre plates and on the surface of catheters. Combinations of P128 and SoC antibiotics were highly synergistic in inhibiting growth in preformed biofilms. Potent activity on planktonic cells, persisters and biofilms of CoNS suggests that P128 is promising candidate for clinical development for treating foreign body-related and other CoNS infections.

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