Therapeutic Use of Bacteriophage and Antibiotic Formulations for the Treatment of Antibiotic Resistant Acinetobacter Baumannii
Therapeutic Use of Bacteriophage and Antibiotic Formulations for the Treatment of Antibiotic Resistant Acinetobacter Baumannii
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Date
2020
Authors
Acuña, Kierstin
Barrie, Mariama
Beaudry, Madeline
Cooley, Rory
Fields, Colin
Grissom, Spencer
Keepers, Zachery
Lavrentieva, Anna
Sutton, Hannah
Walsh, Timothy
Advisor
Knapstein, Kevin
Citation
DRUM DOI
Abstract
Widespread use of antibiotics has enriched global bacteria populations for strains
possessing antibiotic resistance (AR) genes. Proliferation of AR genes and mechanisms
have resulted in numerous multidrug resistant (MDR) infections for which there are no
effective treatments. Acinetobacter baumannii is a major cause of hospital acquired
(nosocomial) infections and is associated with outbreaks of MDR infections. Virulent
bacteriophages (phages) present a way to remedy bacterial infections, while also having
built-in mechanisms to circumvent resistance. This proposed study aims to develop a
phage therapeutic targeting antibiotic resistant A. baumannii. The phages chosen for the
final formulation exhibited high bactericidal activity and were able to infect several
strains of A. baumannii from a provided library. Additionally, the phage-antibiotic
synergy (PAS) effect was investigated in formulations with sub-lethal doses of ampicillin
and chloramphenicol. The effectiveness of the phage therapeutic at different multiplicity
of infections (MOI) and antibiotic concentrations were assessed relative to standard antibiotic doses. Well-plate studies suggest that higher MOI and antibiotic concentrations
resulted in the greatest initial bactericidal effects, longest time to develop resistance, and
lowest overall bacteria concentration. In future formulation studies, we would like to
expand and optimize the current phage-antibiotic formulation and explore cocktail
effects, whereby the formulation consists of a mixture of different phages that increases
selective pressure.
Notes
Gemstone Team LYTIC