Topographic Changes in Heteroresistant Bacterial Communities*

Antimicrobial resistance (AMR) is a current and growing threat to global health. AMR has already caused millions of deaths worldwide and continues to lead a more than 10% treatment failure rate. Without effective antimicrobials, modern medical advances such as transplants, chemotherapy, and treatment of premature infants may also not be safe to perform. Due to the lack of sensitivity of traditional susceptibility tests, AMR has largely been treated as binary – microbial populations are considered either resistant or susceptible to a drug – while AMR is actually analog – heteroresistance, persistence, and tolerance as examples. We focus on bacterial heteroresistance, which occurs when an isogenic strain of bacteria possesses phenotypically resistant and susceptible sub-populations. This susceptibility phenotype is extremely common, contributes to chronic infections, and has been correlated with treatment failure.

Using white-light interferometry, we examine the spatial structure of bacterial communities with heterogeneous population responses to antibiotics through the surface topography of the community. The changes in topography from cell reproduction and cell death play a role in faster, better identification of the heteroresistant phenotype. We examine these changes across different killing and resistance mechanisms.