Strategy for mass production of lytic Staphylococcus aureus bacteriophage pSa-3: contribution of multiplicity of infection and response surface methodology

Abstract Background Antibiotic-resistant bacteria have emerged as a serious problem; bacteriophages have, therefore, been proposed therapeutic alternative to antibiotics. Several authorities, such pharmacopeia, FDA, confirmed their safety, and some are commercially available worldwide. The demand for is expected increase exponentially in the future; hence, there an urgent need mass-produce economically. Unlike replication of non-lytic bacteriophages, lytic replicated by lysing host bacteria, which leads termination phage production; strategies that can prolong lysis bacteria–bacteriophage co-cultures, required. Results In current study, we manipulated inoculum concentrations Staphylococcus aureus pSa-3 (multiplicity infection, MOI), energy sources delay bactericidal effect while optimizing production. We examined increasing range bacterial concentration (2 × 10 8 2 9 CFU/mL) decrease lag phase, combination with decreasing (from MOI 0.01 0.00000001) host. Bacterial CFU/mL 0.0001 showed maximum final production rate (1.68 plaque forming unit (PFU)/mL). With this phage–bacteria inoculum, selected glycerol, glycine, calcium carbon, nitrogen, divalent ion sources, respectively, After optimization using response surface methodology, was 8.63 ± 9.71 PFU/mL (5.13-fold increase). Conclusions Therefore, be maximized reducing seeding MOI, combinatorial strategy could time. Further, suggest methodology has potential mass bacteriophages.