The historical notion of a microbial population has been of a clonal population of
identical swimming planktonic cells in a laboratory flask. As the field has advanced,
we have grown to appreciate the immense diversity in microbial behaviors, from
their propensity to grow in dense surface-attached communities as a biofilm, to the
consequences of social dilemmas between cells, to their ability to form spores able to
survive nearly any environmental insult. However, the historically biased view of
the clonal microbial population still persists – even when a rare phenotype is
investigated, the focus simply shifts to that narrower focal population - and this bias
can lead to some of the broader questions relating to the consequences of phenotypic
diversity within populations to be overlooked.
This work seeks to address this gap by investigating the evolutionary causes and
consequences of phenotypic heterogeneity, with a focus on clinically relevant
phenotypes. We first develop and experimentally validate a theoretical model
describing the evolution of a microbial population faced with a trade-off between
survival and fecundity phenotypes (e.g. biofilm and planktonic cells), which suggests
that simultaneous investment in both types maximizes lineage fitness in
heterogeneous environments. This model helps to inform the experimental studies
in the following chapters. We find that biofilm-mediated phenotypic resistance to
antibiotics is evolutionarily labile, and responsive to antibiotic dose and whether
biofilm or planktonic cells are passaged. We also show that persistence in E. coli is
age-independent, supporting the current hypothesis of stochastic metabolic
fluctuations as the cause of this rare phenotype. Finally, we explore phenotypic
variation across a library of natural isolates of P. aeruginosa, and find few organizing
principles among key phenotypes related to virulence. Together these results suggest
that phenotypic heterogeneity is a crucial component in the ecology and evolution of
microbial populations, and directly affects pressing applied concerns such as the
antibiotic resistance crisis
