Bacterial heterozygosity promotes survival under multidrug selection

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 O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/593358v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@b7a6e8org.highwire.dtl.DTLVardef@12edf40org.highwire.dtl.DTLVardef@4323fborg.highwire.dtl.DTLVardef@1ef6416_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIHeterozygotic bacterial cells (polyploid with multiple chromosome types) can persist across a wider range of conditions than homozygotic cells. C_LIO_LIHeterozygous cells can adaptively adjust chromosomal frequencies in response to external conditions C_LIO_LIFlexibly adjusting chromosome ratios enables heterozygous cells to mitigate the costs of antibiotic resistance and allows rapid responses to temporally and spatially variable environments C_LIO_LIHeterozygosity can increase adaptive plasticity in bacterial cells, in a similar manner to the evolutionary benefits provided by multicopy plasmids. C_LI