Chronic wound microenvironment mediates selection of biofilm-forming multi drug resistant with capability to impair healing.

Venous leg ulcers (VLU) are the most common chronic wounds characterized by bacterial biofilms and perturbed microbiome. is primarily known as skin commensal beneficial for the host, however, some strains can form biofilms and cause infections. By employing shotgun metagenomic sequencing we show that genetic signatures of antimicrobial resistance, adhesion and biofilm formation in VLU isolates correlate with bacterial traits. We demonstrate that the capability of chronic wound isolates to form biofilms and elicit IL-8 and IL-1β expression in human wounds, correlates with the non-healing outcomes in patients with VLU. In contrast, commensal strains were incapable of surviving in the human wounds. We show that major fitness traits of from VLU involve genes for resistance to methicillin and mupirocin, while the biofilm formation relied on the minimal number of genetic elements responsible for bacterial binding to fibronectin and fibrinogen. This underscores the importance of the emergence of treatment resistant virulent lineages in patients with non-healing wounds.