Characterization of nisin F and its role in the control of respiratory tract and skin infections

[摘要] Multidrug resistant strains of Staphylococcus aureus is presenting an increasing threat,especially immune compromised individuals. Many of these strains have developed resistanceto newly approved drugs such as quinupristin-dalfopristin, linezolid and daptomycin. Thesearch for alternative treatment, including bacteriocins (ribosomally synthesized antimicrobialpeptides) of lactic acid bacteria is increasing .Lactococcus lactis subsp. lactis F10, isolated from freshwater catfish, produced a new nisinvariant active against clinical strains of S. aureus. The operon encoding nisin F is located on aplasmid and the structural gene has been sequenced. The lantibiotic is closely related to nisinZ, except at position 30 where valine replaced isoleucine.The antimicrobial activity of nisin F against S. aureus was tested in the respiratory tract ofWistar rats. Non-immunosuppressed and immunosuppressed rats were intranasally infectedwith S. aureus K and then treated with either nisin F or sterile physiological saline. Nisin Fprotected immunosuppressed rats against S. aureus, as symptoms of an infection were onlydetected in the trachea and lungs of immunosuppressed rats treated with saline. The safety ofintranasally administered nisin F was also evaluated and proved to have no adverse sideeffects.The potential of nisin F as an antimicrobial agent to treat subcutaneous skin infections wasevaluated by infecting C57BL/6 mice with a bioluminescent strain of S. aureus (Xen 36).Immunosuppressed mice were treated with either nisin F or sterile physiological saline 24 hand 48 h after infection with subcutaneously injected S. aureus Xen 36. Histology andbioluminescence flux measurements revealed that nisin F was ineffective in the treatment ofdeep dermal staphylococcal infections. Non-infected and infected mice treated with nisin Fhad an influx of polymorphonuclear cells in the deep stroma of the skin tissue. This suggestedthat nisin F, when injected subcutaneously, may have modulated the immune system.Nisin F proved an effective antimicrobial agent against S. aureus-related infections in therespiratory tract, but not against subcutaneous infections. The outcome of nisin F treatmentthus depends on the route of administration and site of infection.

[发布机构] Stellenbosch University