Bacterial heterozygosity promotes survival under multidrug selection

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

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. Graphical abstract Heterozygotic bacterial cells (polyploid with multiple chromosome types) can persist across a wider range of conditions than homozygotic cells. Heterozygous cells can adaptively adjust chromosomal frequencies in response to external conditions Flexibly adjusting chromosome ratios enables heterozygous cells to mitigate the costs of antibiotic resistance and allows rapid responses to temporally and spatially variable environments Heterozygosity can increase adaptive plasticity in bacterial cells, in a similar manner to the evolutionary benefits provided by multicopy plasmids.

Authors 3

1. Shraddha Shitut corresponding Aachen Institute of Biology, Leiden University

   Leiden University · University of Groningen

   Affiliation as printed

   Institute of Biology, Leiden University, the Netherlands

   Origins Centre, Groningen, the Netherlands

2. Dennis Claessen Aachen Institute of Biology, Leiden University

   Leiden University

   Affiliation as printed

   Institute of Biology, Leiden University, the Netherlands

3. Daniel E. Rozen corresponding Aachen Institute of Biology, Leiden University

   Leiden University

   Affiliation as printed

   Institute of Biology, Leiden University, the Netherlands