Abstract
Escherichia coli is both a harmless commensal in the intestines of many mammals, as well as a dangerous pathogen. The evolutionary paths taken by strains of this species in the commensal-to-pathogen transition are complex and can involve changes both in the core genome, as well in the pan-genome. One way to understand the likely paths that a commensal strain of E. coli takes when evolving pathogenicity is through experimentally evolving the strain under the selective pressures that it will have to withstand as a pathogen. Here, we report that a commensal strain, under continuous pressure from macrophages, recurrently acquired a transposable element insertion, which resulted in two key phenotypic changes: increased intracellular survival, through the delay of phagosome maturation and increased ability to escape macrophages. We further show that the acquisition of the pathoadaptive traits was accompanied by small but significant changes in the transcriptome of macrophages upon infection. These results show that under constant pressures from a key component of the host immune system, namely macrophage phagocytosis, commensal E. coli rapidly acquires pathoadaptive mutations that cause transcriptome changes associated to the host-microbe duet.
Highlights
Most Escherichia coli are commensal bacteria that colonize the mammalian gastrointestinal tract soon after birth
Examples of pathoadaptive mutations in naturally-occurring pathogens include: the loss of mucA in Pseudomonas aeruginosa, which increases its ability to evade phagocytosis and resist pulmonary clearance[8]; the loss of oprD by P. aeruginosa, with an associated carbapenem-resistance phenotype, which results in increased levels of cytotoxicity against macrophages (MΦs) and increased colonization and dissemination to the spleen of mice[9]; polymorphism in hopZ in Pseudomonas syringiae, which allows for immune evasion in plants[10]; and allelic variation in FimH, the type 1 adhesin of E. coli, which can change the ability of uropathogenic strains to colonize and invade bladder tissue[11]
We have previously isolated mutants of a commensal E. coli strain that adapted to the presence of MΦs, through an experimental evolution setup[14]
Summary
Most Escherichia coli are commensal bacteria that colonize the mammalian gastrointestinal tract soon after birth. We developed an experimental evolution setup to determine the emergence of possible pathogenic traits in commensal E. coli, by following its adaptation under an antagonistic interaction with one of the key sentinels of the innate immune system, MΦs14. Bacteria-containing phagosomes follow a maturation process whereby they progressively acidify and acquire hydrolytic enzymes This occurs through fusion with organelles of the endocytic pathway, namely endosomes and lysosomes, leading to the formation of phagolysosomes[15]. Salmonella arrests phagosome maturation at a late stage In this case, the acidification of the phagosome is an environmental cue for the expression of pathogenicity island 223, which is necessary for bacterial replication in this adverse environment[24]. Staphylococcus aureus prevents autophagosome maturation, escaping to the cytosol and replicating there[26]
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