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Induction of the staphylococcal proteolytic cascade by antimicrobial fatty acids in community acquired methicillin
Benjamin Arsic1, Yue Zhu, David E Heinrichs
1Department of Microbiology and Immunology, Western University, London, Ontario, Canada.
Abstract:
Community acquired methicillin resistant Staphylococcus aureus (CA-MRSA), and the USA300 strain of CA-MRSA in particular, are known for their rapid community transmission, and propensity to cause aggressive skin and soft tissue infections. To assess factors that contribute to these hallmark traits of CA-MRSA, we evaluated how growth of USA300 and production of secreted virulence factors was influenced on exposure to physiologic levels of unsaturated free fatty acids that would be encountered on the skin or anterior nares, which represent the first sites of contact with healthy human hosts. There was a sharp threshold between sub-inhibitory and inhibitory concentrations, such that 100 µM sapienic acid (C16∶1) and linoleic acid (C18∶1) were sufficient to prevent growth after 24 h incubation, while 25 µM allowed unrestricted growth, and 50 µM caused an approximate 10-12 h lag, followed by unimpeded exponential growth. Conversely, saturated palmitic or stearic acids did not affect growth at 100 µM. Although growth was not affected by 25 µM sapienic or linoleic acid, these and other unsaturated C16 and C18 fatty acids, but not their saturated counterparts, promoted robust production of secreted proteases comprising the Staphylococcal proteolytic cascade. This trait was also manifested to varying degrees in other CA-MRSA, and in genetically diverse methicillin susceptible S. aureus strains. Therefore, induction of the Staphylococcal proteolytic cascade by unsaturated fatty acids is another feature that should now be evaluated as a potential contributing factor in the aggressive nature of skin and soft tissue infections caused by USA300, and as a general virulence mechanism of S. aureus.
Insights
Community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 growth is inhibited by unsaturated fatty acids. However, these fatty acids promote virulence factor production, contributing to aggressive skin infections.
Area of Science:
- Microbiology
- Dermatology
- Infectious Diseases
Background:
- Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), particularly the USA300 strain, exhibits rapid transmission and causes severe skin infections.
- The skin and anterior nares are primary human host contact sites for CA-MRSA.
- Understanding factors influencing CA-MRSA virulence is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the impact of physiological levels of unsaturated free fatty acids on USA300 growth and virulence factor production.
- To determine the differential effects of unsaturated versus saturated fatty acids on CA-MRSA.
Main Methods:
- Exposure of USA300 to varying concentrations of sapienic acid, linoleic acid, palmitic acid, and stearic acid.
- Monitoring bacterial growth over 24-hour incubation periods.
- Assessing the production of secreted proteases involved in the Staphylococcal proteolytic cascade.
Main Results:
- Unsaturated fatty acids ( sapienic and linoleic acids) demonstrated a concentration-dependent effect on growth, inhibiting it at 100 µM but allowing growth at lower concentrations after a lag phase.
- Saturated fatty acids (palmitic and stearic acids) did not inhibit growth even at 100 µM.
- Unsaturated fatty acids, but not saturated ones, significantly promoted the production of secreted proteases in USA300 and other S. aureus strains.
Conclusions:
- Unsaturated fatty acids can inhibit CA-MRSA growth at physiological concentrations found on human skin.
- Induction of the Staphylococcal proteolytic cascade by unsaturated fatty acids represents a potential virulence mechanism contributing to aggressive skin and soft tissue infections.
- This mechanism warrants further investigation as a general virulence factor for Staphylococcus aureus.
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