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The impact of lipid metabolism on staphylococcal mastitis |
Co-P.I. Mark McGuire
Abstract |
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Staphylococcus aureus produces a wide variety of virulence factors that play important roles in the establishment and
progression of disease. The expression of these virulence factors is under complex regulatory control involving multiple
transcriptional regulators. Although many of these regulatory components are well-characterized, little is known about the
extracellular signals that affect virulence factor gene expression. One exception to this is glycerol monolaurate (GML) and
its free fatty acid, lauric acid, which have been shown to have inhibitory effects on not only the production of several
virulence factors, but also the growth of the bacteria. As GML and a variety of fatty acids are predominant within the mammary
gland, these compounds could have a dramatic effect on the viability and virulence of S. aureus within mammary tissue. Indeed,
our preliminary studies support this idea and that it is the fatty acids released in milk that have an inhibitory effect on S.
aureus. Thus, the overall objective of this proposal is to test the hypothesis that lipase activity is induced upon infection
causing the release of free fatty acids within milk and impacting the progression of staphylococcal mastitis. This hypothesis
will be tested in three specific aims. In specific aim 1, the fatty acids and form of lipid that regulate the growth and
expression of virulence factors in S. aureus will be determined. In this aim we will determine the range of fatty acids
present in milk that affect growth and virulence factor production in S. aureus. The contributions of these fatty acids on
growth inhibition in milk obtained from infected and noninfected mammary glands will also be studied. 2) To examine the
regulation and significance of lipase activity in S. aureus and the mammary gland as a mechanism to provide benefits to the
pathogen and/or host. Here, we will study the role of both pathogen- and host-encoded lipases on milk lipid metabolism and
determine their potential roles in the progression of disease within mammary tissue. 3) To compare the effects of altered milk
lipid composition on the host-pathogen response to an infection with S. aureus. This aim will address the impact of altering
the lipid composition of milk, through dietary supplementation, on the resistance and severity of staphylococcal mastitis. The
results generated will yield valuable new insights into the biological role that lipids play in the progression of
staphylococcal mastitis and potentially lead to new treatment strategies to help reduce the impact of these types of
infections.
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