Proteins of the SubB family provide multiple mechanisms of serum resistance in <i>Yersinia pestis</i>

The serum complement system is a cornerstone element of the innate immune response. Bacterial resistance to this system is a multifaceted process involving various proteins and molecular mechanisms. Here, we report several genes required for the growth of <i>Yersinia pestis</i> in serum. Among them, we found that <i>ypo0337</i> encodes an outer-membrane-associated lectin that recruits factor H, C4BP and hemopexin, conferring resistance to the serum complement system. YPO0337 displays high sequence similarity with the SubB subunit of the AB₅ toxin from <i>Escherichia coli</i>, as well as other SubB-like proteins, and <i>subB</i> from <i>E. coli</i> restores the ability of <i>Y. pestis</i> Δ<i>ypo0337</i> mutant to resist to serum complement. Altogether, the data suggest that at least two members of the SubB protein family function as virulence factors, conferring resistance to serum complement through a unique mode of action.