Persister and VBNC cells can phenotypically survive environmental stressors, such as antibiotic treatment, limitation of nutrients, and acid stress, and have been linked to chronic infections and antimicrobial resistance. It has recently been suggested that pH regulation might play a role in an organism’s phenotypic survival to antibiotics; however, this hypothesis remains to be tested.
Environmental and
intracellular stresses can perturb protein homeostasis
and trigger the formation and accumulation of protein aggregates.
It has been recently suggested that the level of protein aggregates
accumulated in bacteria correlates with the frequency of persister
and viable but nonculturable cells that transiently survive treatment
with multiple antibiotics. However, these findings have often been
obtained employing fluorescent reporter strains. This enforced heterologous
protein expression facilitates the visualization of protein aggregates
but could also trigger the formation and accumulation of protein aggregates.
Using microfluidics-based single-cell microscopy and a library of
green fluorescent protein reporter strains, we show that heterologous
protein expression favors the formation of protein aggregates. We
found that persister and viable but nonculturable bacteria surviving
treatment with antibiotics are more likely to contain protein aggregates
and downregulate the expression of heterologous proteins. Our data
also suggest that such aggregates are more basic with respect to the
rest of the cell. These findings provide evidence for a strong link
between heterologous protein expression, protein aggregation, intracellular
pH, and phenotypic survival to antibiotics, suggesting that antibiotic
treatments against persister and viable but nonculturable cells could
be developed by modulating protein aggregation and pH regulation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.