Horizontal gene transfer by natural transformation promotes both genetic and epigenetic inheritance of traits

Natural transformation (NT) is a major mechanism of horizontal gene transfer in microbial species that promotes the spread of antibiotic resistance determinants and virulence factors. Here, we develop a cell biological approach to characterize the spatial and temporal dynamics of homologous recombination during NT in Vibrio cholerae . Our results directly demonstrate (1) that transforming DNA efficiently integrates into the genome as single-stranded DNA, (2) that the resulting heteroduplexes are resolved by chromosome replication and segregation, and (3) that integrated DNA is rapidly expressed prior to cell division. We show that the combination of these properties results in the epigenetic transfer of gene products within transformed populations, which can support the transgenerational epigenetic inheritance of antibiotic resistance in both V. cholerae and Streptococcus pneumoniae . Thus, beyond the genetic acquisition of novel DNA sequences, NT can also promote the epigenetic inheritance of traits during this conserved mechanism of horizontal gene transfer.