Abstract
ABSTRACTBacteriophages infect an estimated 1023 to 1025 bacterial cells each second, many of which carry physiologically relevant plasmids (e.g., those encoding antibiotic resistance). However, even though phage-plasmid interactions occur on a massive scale and have potentially significant evolutionary, ecological, and biomedical implications, plasmid fate upon phage infection and lysis has not been investigated to date. Here we show that a subset of the natural lytic phage population, which we dub “superspreaders,” releases substantial amounts of intact, transformable plasmid DNA upon lysis, thereby promoting horizontal gene transfer by transformation. Two novel Escherichia coli phage superspreaders, SUSP1 and SUSP2, liberated four evolutionarily distinct plasmids with equal efficiency, including two close relatives of prominent antibiotic resistance vectors in natural environments. SUSP2 also mediated the extensive lateral transfer of antibiotic resistance in unbiased communities of soil bacteria from Maryland and Wyoming. Furthermore, the addition of SUSP2 to cocultures of kanamycin-resistant E. coli and kanamycin-sensitive Bacillus sp. bacteria resulted in roughly 1,000-fold more kanamycin-resistant Bacillus sp. bacteria than arose in phage-free controls. Unlike many other lytic phages, neither SUSP1 nor SUSP2 encodes homologs to known hydrolytic endonucleases, suggesting a simple potential mechanism underlying the superspreading phenotype. Consistent with this model, the deletion of endonuclease IV and the nucleoid-disrupting protein ndd from coliphage T4, a phage known to extensively degrade chromosomal DNA, significantly increased its ability to promote plasmid transformation. Taken together, our results suggest that phage superspreaders may play key roles in microbial evolution and ecology but should be avoided in phage therapy and other medical applications.
Highlights
Bacteriophages infect an estimated 1023 to 1025 bacterial cells each second, many of which carry physiologically relevant plasmids
Because the uptake of exogenous DNA is a principal form of horizontal gene transfer [3], because phages are actively being developed as treatments for antibiotic-resistant bacterial infections [1], and because antibiotic resistance genes are frequently located on plasmids [4, 5], the fate of plasmids upon phage infection and lysis has potentially significant evolutionary, ecological, and biomedical implications
DISCUSSION bacteriophages have long been known to contribute to horizontal gene transfer [6], previous investigations have focused almost exclusively on certain phages’ capacity for transduction [8,9,10]
Summary
Bacteriophages infect an estimated 1023 to 1025 bacterial cells each second, many of which carry physiologically relevant plasmids (e.g., those encoding antibiotic resistance). Unlike many other lytic phages, neither SUSP1 nor SUSP2 encodes homologs to known hydrolytic endonucleases, suggesting a simple potential mechanism underlying the superspreading phenotype Consistent with this model, the deletion of endonuclease IV and the nucleoid-disrupting protein ndd from coliphage T4, a phage known to extensively degrade chromosomal DNA, significantly increased its ability to promote plasmid transformation. IMPORTANCE Bacteriophages (phages), viruses that infect bacteria, are the planet’s most numerous biological entities and kill vast numbers of bacteria in natural environments Many of these bacteria carry plasmids, extrachromosomal DNA elements that frequently encode antibiotic resistance. Because the uptake of exogenous DNA (transformation) is a principal form of horizontal gene transfer [3], because phages are actively being developed as treatments for antibiotic-resistant bacterial infections [1], and because antibiotic resistance genes are frequently located on plasmids [4, 5], the fate of plasmids upon phage infection and lysis has potentially significant evolutionary, ecological, and biomedical implications. Phage infection and lysis are presumed to significantly enrich pools of extracellular DNA in natural environments [11], many fundamental questions, including the variability in different phages’ capacity to release intact host DNA, the distinguishing mechanism(s) associated with such release, and the transformability of phage-released host DNA, have not been investigated to date
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