| Summary: | Thesis (PhD (Microbiology))--University of Stellenbosch, 2009. === Multidrug resistant strains of Staphylococcus aureus is presenting an increasing threat,
especially immune compromised individuals. Many of these strains have developed resistance
to newly approved drugs such as quinupristin-dalfopristin, linezolid and daptomycin. The
search for alternative treatment, including bacteriocins (ribosomally synthesized antimicrobial
peptides) of lactic acid bacteria is increasing .
Lactococcus lactis subsp. lactis F10, isolated from freshwater catfish, produced a new nisin
variant active against clinical strains of S. aureus. The operon encoding nisin F is located on a
plasmid and the structural gene has been sequenced. The lantibiotic is closely related to nisin
Z, except at position 30 where valine replaced isoleucine.
The antimicrobial activity of nisin F against S. aureus was tested in the respiratory tract of
Wistar rats. Non-immunosuppressed and immunosuppressed rats were intranasally infected
with S. aureus K and then treated with either nisin F or sterile physiological saline. Nisin F
protected immunosuppressed rats against S. aureus, as symptoms of an infection were only
detected in the trachea and lungs of immunosuppressed rats treated with saline. The safety of
intranasally administered nisin F was also evaluated and proved to have no adverse side
effects.
The potential of nisin F as an antimicrobial agent to treat subcutaneous skin infections was
evaluated 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 h
and 48 h after infection with subcutaneously injected S. aureus Xen 36. Histology and
bioluminescence flux measurements revealed that nisin F was ineffective in the treatment of
deep dermal staphylococcal infections. Non-infected and infected mice treated with nisin F
had an influx of polymorphonuclear cells in the deep stroma of the skin tissue. This suggested
that nisin F, when injected subcutaneously, may have modulated the immune system.
Nisin F proved an effective antimicrobial agent against S. aureus-related infections in the
respiratory tract, but not against subcutaneous infections. The outcome of nisin F treatment
thus depends on the route of administration and site of infection.
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