Analysis of In-Patient Evolution of Escherichia coli Reveals Potential Links to Relapse of Bone and Joint Infections

Bone and joint infections (BJIs) are difficult to treat and affect a growing number of patients, in which relapses are observed in 10-20% of case. These relapses, which call for prolonged antibiotic treatment and increase resistance emergence risk, may originate from ill-understood adaptation of the pathogen to the host. Here, we investigated 3 pairs of Escherichia coli strains from BJI cases and their relapses to unravel adaptations within patients. Whole-genome comparison presented evidence for positive selection and phenotypic characterization showed that biofilm formation remained unchanged, contrary to what is usually described in such cases. Although virulence was not modified, we identified the loss of 2 virulence factors contributing to immune system evasion in one of the studied strains. Other strategies, including global growth optimization and colicin production, likely allowed the strains to outcompete competitors. This work highlights the variety of strategies allowing in-patient adaptation in BJIs. We demonstrated that 3 Escherichia coli strains involved in bone and joint infection (BJI) relapses adapted in patients through various molecular mechanisms, allowing them to outcompete other bacteria or evade the immune system. Understanding in-patient adaptation may help fight BJI relapses.