posted on 2020-01-03, 18:03authored byHeather
S. Deter, Alawiah H. Abualrahi, Prajakta Jadhav, Elise K. Schweer, Curtis T. Ogle, Nicholas C. Butzin
Antibiotic
tolerance is a widespread phenomenon that renders antibiotic
treatments less effective and facilitates antibiotic resistance. Here
we explore the role of proteases in antibiotic tolerance, short-term
population survival of antibiotics, using queueing theory (i.e., the study of waiting lines), computational models,
and a synthetic biology approach. Proteases are key cellular components
that degrade proteins and play an important role in a multidrug tolerant
subpopulation of cells, called persisters. We found that queueing
at the protease ClpXP increases antibiotic tolerance ∼80 and
∼60 fold in an E. coli population treated
with ampicillin and ciprofloxacin, respectively. There does not appear
to be an effect on antibiotic persistence, which we distinguish from
tolerance based on population decay. These results demonstrate that
proteolytic queueing is a practical method to probe proteolytic activity
in bacterial tolerance and related genes, while limiting the unintended
consequences frequently caused by gene knockout and overexpression.