DETERMINING THE EFFECTS OF HUMAN SERUM ON PSEUDOMONAS AERUGINOSA PHYSIOLOGY

Abstract

The bacteria Pseudomonas aeruginosa (P. aeruginosa) causes severe infections that are difficult to treat^1,2. Research into new treatments often start with in vitro antimicrobial assays traditionally performed in media³ that do not accurately reflect the in vivo wound environment. Recent studies use more biologically relevant environments by adding serum. Serum is a part of blood and can be divided into complement (immune system) and non-complement. While the effects of complement on P. aeruginosa have been investigated extensively4–6, little to no research exists on the effects of complement-inactivated human serum. Our research shows that complement-inactivated serum elicits antimicrobial resistance and tolerance from P. aeruginosa. Through bioactivity-guided fractionation, we found a protein component >100 kDa in serum that elicits strong silver resistance, a component between 50-100 kDa that elicits intermediate resistance, and a potentially nutrition-based resistance phenomenon. My research shows that bioactive moieties, chemistry, and physiology likely all play a part in serum-dependent antimicrobial resistance and tolerance. Further research will examine how complement-inactivated serum affects P. aeruginosa physiology through RNA-sequencing, which allows me to assess what genes are turned “on” and “off”. Outputs will inform further research into creating better wound environment models for in vitro antimicrobial R&D and wound-related research.