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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts
37
Microengineering for Microbiology
Neeraj Dhar
, John McKinney.
Laboratory of Microbiology and Microtechnology, Ecole Polytechnique Fédérale de Lausanne,
1015 Lausanne, Switzerland.
Bacterial behavior is highly individualistic in the sense that individual cells living in the same
environment can exhibit markedly different phenotypes. Mutation and genetic exchange are
important drivers of bacterial individuation but these events are relatively rare. At higher
frequencies, genetically identical cells often display metastable variation in their growth rates,
response kinetics, stress resistance, and other quantifiable phenotypes. These cell-to-cell
differences arise from non-genetic sources: unequal partitioning of components at cell division,
stochastic fluctuations in gene expression, phenotypic memory of past events, etc. Time-
dependent variation at the single-cell level generates phenotypic diversity at the population level.
This diversity contributes to bacterial persistence in fluctuating and stressful environments
because it increases the odds that some individuals may survive a potentially lethal change that
would otherwise extinguish the population. A medically relevant example of this phenomenon is
the refractoriness of bacterial infections to antibiotic therapy, which has been attributed to
spontaneous phenotypic variants that survive despite prolonged exposure to bactericidal
antibiotics. Bacterial persistence is not due to antibiotic resistance mutations in the classical
sense, and it is not clear why some cells tolerate antibiotics that kill their genetically identical
siblings. Our studies are focused on the mechanistic basis of bacterial persistence. We use
correlated optical and atomic force microscopy in conjunction with purpose-built microfluidic
and microelectromechanical systems for single-cell time-lapse imaging and nanomechanical
measurements of bacteria subjected to antibiotics and other environmental stresses.