A frameshift in <i>Yersinia pestis rcsD</i> alters canonical Rcs signalling to preserve flea-mammal plague transmission cycles.

Abstract

Multiple genetic changes in the enteric pathogen <i>Yersinia pseudotuberculosis</i> have driven the emergence of <i>Yesinia pestis</i>, the arthropod-borne, etiological agent of plague. These include developing the capacity for biofilm-dependent blockage of the flea foregut to enable transmission by flea bite. Previously, we showed that pseudogenization of <i>rcsA</i>, encoding a component of the Rcs signalling pathway, is an important evolutionary step facilitating <i>Y. pestis</i> flea-borne transmission. Additionally, <i>rcsD,</i> another important gene in the Rcs system, harbours a frameshift mutation. Here, we demonstrated that this <i>rcsD</i> mutation resulted in production of a small protein composing the C-terminal RcsD histidine-phosphotransferase domain (designated RcsD-Hpt) and full-length RcsD. Genetic analysis revealed that the <i>rcsD</i> frameshift mutation followed the emergence of <i>rcsA</i> pseudogenization. It further altered the canonical Rcs phosphorylation signal cascade, fine-tuning biofilm production to be conducive with retention of the <i>pgm</i> locus in modern lineages of <i>Y. pestis</i>. Taken together, our findings suggest that a frameshift mutation in <i>rcsD</i> is an important evolutionary step that fine-tuned biofilm production to ensure perpetuation of flea-mammal plague transmission cycles.