Evolution towards small colony variants of pandemic multidrug resistant ST131 Escherichia coli isolates from a 10-year bone infection

Chronic wounds are difficult to treat because underlying medical conditions can impair the mechanical and physiological first-line innate immune defenses, leading to persistent microbial infections. We report here the isolation, molecular and phenotypic characterization of seven E. coli strains that were isolated concomitantly with Enterococcus faecalis after an open foot fracture caused by the 2004 tsunami resulting in a 10-year chronic bone and joint infection. Initially present antimicrobial resistant E. coli ST405 and ST940 isolates were followed by host adapted isolates of ubiquitous ST131 clone presumably acquired from the environment already upon initial foot fracture. The E. coli ST131 clade C1 strains showed genomic alterations associated with virulence and persistence including large chromosomal inversions and, subsequently, a large deletion to cause small colony variants and higher susceptibility to formaldehyde and other stress provoking In this context deletion of hemB catalyzing an early step in the pathway for heme biosynthesis was the major, but presumably not the only cause of small colony variant emergence. Surprisingly, ST131 isolates did not display pronounced biofilm formation in conventional biofilm assays suggesting unconventional modes of persistence. In summary, the genomes of ST131 clone members are highly plastic which enables their persistence in novel ecological niches. In individuals with underlying metabolic diseases such as diabetes wound infection can prepare for colonization with ST131 E. coli isolates. FundingThis work was partially funded by ALF, the Petrus and Augusta Hedlunds Foundation and the Karolinska Institutet.