Experimental support for multidrug resistance transfer potential in the preterm infant gut microbiota

Background: There is currently a lack of experimental evidence for horizontal gene transfer (HGT) mechanisms in the human gut microbiota. The aim of this study was therefore to experimentally determine the HGT potential in the microbiota of a healthy preterm infant twin pair and to evaluate the global occurrence of the mobilized elements. Methods: Stool samples were collected. Both shotgun metagenome sequencing and bacterial culturing were done for the same samples. A range of experimental conditions were used to test DNA transfer for the cultured isolates. Searches for global distribution of transferable elements were done for the ~120,000 metagenomic samples in the Sequence Read Archive (SRA) database. Results: DNA transfer experiments demonstrated frequent transmission of an ESBL encoding IncI1 plasmid, a high copy number ColEI plasmid, and bacteriophage P1. Both IncI1 and ColE1 were abundant in the stool samples. In vitro competition experiments showed that transconjugants containing IncI1 plasmids outcompeted the recipient strain in the absence of antibiotic selection. The SRA searches indicated a global distribution of the mobilizable elements, with chicken identified as a possible reservoir for the IncI1 ESBL encoding plasmid. Conclusion: Our results experimentally support a major horizontal transmission and persistence potential of the preterm infant gut microbiota mobilome involving genes encoding ESBL.
We thank Norwegian University of Life Sciences for the financial support, and the Spanish Ministry of Science and Universities for the grant AGL2015-70487-P. Travels and stays in Spain and Norway for this study were supported by EEA Coordinated Mobility of Researchers NILS Science and Sustainability Project 017-CM-01-2013.