The role and metabolism of lipids in the host-pathogen interaction of Staphylococcus aureus mastitis in cattle

Experiments were conducted to determine the role of fatty acids and lipid metabolism in the host-pathogen interaction during a bovine mastitis infection. Initially, minimum inhibitory concentrations (MIC) were conducted to see which fatty acids and their esterified forms were most inhibitory to bovine mastitis-causing Staphylococcus aureus isolates. Based on this information, growth curve analysis was conducted and it was discovered that saturated medium chain fatty acids capric, lauric and myristic acid inhibited the bacteria by decreasing the maximum amount of growth, the most potent was lauric acid. Polyunsaturated long chain fatty acids including linoleic acid and conjugated linoleic acid inhibited growth in a different manner by delaying the time to exponential growth in a dose-dependent manner. These results indicated that the increase in free fatty acids observed in the milk of mastitic cows is a host response to inhibit S. aureus during an infection. Further in vivo analysis of an induced S. aureus mastitis infection showed that gene expression of lipases increased; indicating that release of free fatty acids is a host mechanism to inhibit bacteria. S. aureus also have developed mechanisms to escape the host immune system and overcome the inhibitory effects of lipids via several enzymes. Among these enzymes, S. aureus produces its own lipase which can also cleave free fatty acids from triglycerides or inhibitory monoglycerides, all bovine mastitis strains tested (n = 91) positive for lipase activity. Fatty acid modifying enzyme (FAME) is also produced by S. aureus and esterifies free fatty acids to cholesterol. There were 86% of mastitis-causing S. aureus strains that tested positive for FAME activity. This enzyme was purified and sequenced to begin to identify the role it plays in lipid metabolism in a mastitis infection. Understanding the role of this enzyme in the host-pathogen interaction could lead to potential targets for antibiotics to control the growth of staphylococcus bacteria in many infections.