Abstract
Elucidating the adaptive strategies and plasticity of bacterial genomes in situ is crucial for understanding the epidemiology and evolution of pathogens threatening human health. While much is known about the evolution of Escherichia coli in controlled laboratory environments, less effort has been made to elucidate the genome dynamics of E. coli in its native settings. Here, we follow the genome dynamics of co-existing E. coli lineages in situ of the infant gut during the first year of life. One E. coli lineage causes a urinary tract infection (UTI) and experiences several alterations of its genomic content during subsequent antibiotic treatment. Interestingly, all isolates of this uropathogenic E. coli strain carried a highly stable plasmid implicated in virulence of diverse pathogenic strains from all over the world. While virulence elements are certainly beneficial during infection scenarios, their role in gut colonization and pathogen persistence is poorly understood. We performed in vivo competitive fitness experiments to assess the role of this highly disseminated virulence plasmid in gut colonization, but found no evidence for a direct benefit of plasmid carriage. Through plasmid stability assays, we demonstrate that this plasmid is maintained in a parasitic manner, by strong first-line inheritance mechanisms, acting on the single-cell level, rather than providing a direct survival advantage in the gut. Investigating the ecology of endemic accessory genetic elements, in their pathogenic hosts and native environment, is of vital importance if we want to understand the evolution and persistence of highly virulent and drug resistant bacterial isolates.
Highlights
The human gut is home to a dense microbial ecosystem, the human gut microbiota, playing an important role in human health and physiology (Marchesi et al, 2015)
This infant was subjected to long-term antibiotic treatment as a consequence of a urinary tract infection, and was selected for this study due to an observed change in the resistance profile of E. coli strains isolated from this infant (Karami et al, 2007)
Culture independent methods based on metagenomic sequencing have been used to investigate the abundance profiles of strains colonizing the gut over time (Morowitz et al, 2011; Brown et al, 2013; Sharon et al, 2013). These methods are limited in their ability to observe genomic events at high resolution such as horizontal transfer and single nucleotide variations
Summary
The human gut is home to a dense microbial ecosystem, the human gut microbiota, playing an important role in human health and physiology (Marchesi et al, 2015). The broad adaptation of E. coli to the gut environment and extraintestinal body sites is reflected in the remarkable genetic diversity within the species This genetic flexibility is largely facilitated by horizontal gene transfer (HGT) of accessory genetic elements including plasmids and phages (Brzuszkiewicz et al, 2009). Acquiring virulence genes might influence the risk and severity of infections caused by the pathogen, but has been suggested to assist in the general persistence of commensal bacterial strains of the gut (Diard et al, 2010; Chen et al, 2013) Virulence determinants such as those involved in adhesion, biofilm formation and iron acquisition correlate with prolonged colonization in the digestive tract (Adlerberth et al, 1998; Nowrouzian et al, 2003)
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