Impact of Spatial Structure on Heteroresistance

Microbes are very social, as they perform much of their metabolism outside of their bodies by secreting various `public goods’ into the environment around them. Many of these public goods are antagonistic, deadly toxins produced to kill susceptible competitors. These toxins can be highly effective and are the source of most antibiotics. For survival, bacteria have evolved defense mechanisms to resist antibiotics delivered by competitors. While traditionally treated as binary – microbial populations are either resistant or susceptible to a drug – due to the lack of sensitivity in susceptibility tests, antibiotic susceptibility is analog. Heteroresistance sits between the extremes and occurs when an isogenic strain shows different levels of phenotypic resistance. This is common, occurring in over 25% of toxin-strain combinations, contributing to increasing numbers of chronic infections, treatment complications, and death in humans.

As many toxin secretion methods are contact dependent, we expect spatial structure not only to both facilitate and prevent killing in the microbe-antibiotic competition, but to also play a large role in faster, better identification of heteroresistance. We examine this using white-light interferometry and confocal microscopy.