Clinical & translational immunology
Objectives. The increasing prevalence of antibiotic-resistantStaphylococcus aureus, besides the inadequate numbers ofeffective antibiotics, emphasises the need to find new therapeuticagents against this lethal pathogen.
Methods. In this study, toobtain antibody fragments against S. aureus, a human single-chainfragment variable (scFv) library was enriched against livingmethicillin-resistant S. aureus (MRSA) cells, grown in threedifferent conditions, that is human peripheral blood mononuclearcells with plasma, whole blood and biofilm. The antibacterialactivity of scFvs was evaluated by the growth inhibition assayin vitro. Furthermore, the therapeutic efficacy of anti-S. aureusscFvs was appraised in a mouse model of bacteraemia.
Results.Three scFv antibodies, that is MEH63, MEH158 and MEH183, withunique sequences, were found, which exhibited significantbinding to S. aureus and reduced the viability of S. aureus inin vitro inhibition assays. Based on the results, MEH63, MEH158and MEH183, in addition to their combination, could prolong thesurvival rate, reduce the bacterial burden in the blood andprevent inflammation and tissue destruction in the kidneys andspleen of mice with MRSA bacteraemia compared with the vehiclegroup (treated with normal saline).
Conclusion. The combinationtherapy with anti-S. aureus scFvs and conventional antibioticsmight shed light on the treatment of patients with S. aureusinfections.