Fig. 5: Navigation of selective tradeoffs on O-antigen presentation via de novo mutation.

a Inferred natural history of B. dolosa LPS O-antigen presentation during an outbreak in people with CF. The initial B. dolosa outbreak was initiated by a strain lacking O-antigen due to a premature stop codon in a glycosyltransferase gene. This premature stop mutation likely occurred shortly before or during outbreak initiation, as experimental reversion successfully restores O-antigen presentation¹⁵. As the outbreak spread and persisted in chronic infections, independent reversions restored B. dolosa’s O-antigen in multiple patients. Within each patient, strains with variable O-antigen presentation were recoverable and coexisted for years. Two patients recently infected by a survivor of this outbreak were initially colonized by strains expressing O-antigen. Remarkably, O-antigen-disrupted phenotypes re-emerged independently within each of these patients via a variety of de novo mutations in the O-antigen pathway. b Our in vivo experimental results suggest that O-antigen presence is advantageous in the lung while O-antigen absence is favored in the spleen. Combined with the historical observations, these results suggest that survival in the spleen or immune cells may be important during the early years of chronic B. dolosa lung infection.