Antibiotic Treatment of Persistent Pseudomonas aeruginosa Infections

Emerging Human Infections (The Ohio State University Denman Undergraduate Research Forum)Pseudomonas aeruginosa is an opportunistic pathogen associated with infections due to severe burns and in cystic fibrosis patients. Treatment against these bacteria can be difficult because of the increase in antimicrobial resistance and formation of biofilms. P. aeruginosa lawn biofilms when treated with tobramycin showed generation of antibiotic tolerant cells. These persisters are protected within the biofilm, as a result these cells are often tolerant toward antibiotics. The persister cells under favorable growth conditions grow and can re-establish infection. The objective of this study was to test different class of antibiotics for generation of persister cells. To test for the efficacy of antibiotics, a bioluminescent strain of P. aeruginosa, XEN41, was tested against various class of antibiotics including aminoglycosides, fluoroquinolones, carbapenems, and polymyxins. Preformed biofilms (24 h) of XEN41 were formed on tryptic soy agar (TSA). Antibiotic containing beads (4.8mm diameter) made from calcium sulfate were used to deliver the antibiotic. In vivo imaging system (IVIS) was used to test the response of the antibiotic towards Xen41. The benefit of using the bioluminescent strain is that clear differentiation of zone of clearance and the zone of growth is evident using IVIS. The results showed that Xen41 is susceptible to ciprofloxacin, colistin, gentamicin, and tobramycin and resistant to rifampicin and meropenem. Of the susceptible antibiotics, gentamicin and tobramycin (aminoglycosides) produced persister colonies. These colonies appeared even with high concentrations of antibiotics up to 50ug/mL; the MIC of P. aeruginosa is around 4ug/mL. In conclusion, aminoglycosides facilitate generation of persister cells and combination of antibiotic may be used to treat P. aeruginosa infections, given that the bacteria are not resistant to the antibiotic.No embargoAcademic Major: Pharmaceutical Science