Bacterial heterozygosity promotes survival under multidrug selection

Abstract

Although bacterial cells typically contain a single chromosome, some species are naturally polyploid and carry multiple copies of their chromosome. Polyploid chromosomes can be identical or heterogeneous, the latter giving rise to bacterial heterozygosity. While the benefits of heterozygosity are well studied in eukaryotes, its consequences in bacteria are unknown. Here we examine this question in the context of antibiotic resistance to understand how bacterial heterozygosity affects bacterial survival. Using a cell wall deficient model system in the actinomycete Kitasatospora viridifaciens, we found that heterozygous cells containing different chromosomes expressing different antibiotic resistance markers persist across a broader range of antibiotic concentrations. Recombinant cells containing the same resistance genes on a single chromosome also survive these conditions, but these cells pay a significant fitness cost due to constitutive expression of these genes. By contrast, heterozygous cells mitigate these costs by flexibly adjusting the ratio of their different chromosomes, thereby allowing rapid responses in temporally and spatially variable environments. Our results provide evidence that bacterial heterozygosity can increase adaptive plasticity in bacterial cells, in a similar manner to the evolutionary benefits provided by multicopy plasmids in bacteria.