A multi-co-chaperone pre-secretion assembly directs type VI secretion system toxin delivery

Abstract

Bacterial toxins are secreted through cell-envelope apparatuses, but the pre-secretion delivery process to the type VI secretion apparatus for the toxin proteins that are encoded separately in the genome is largely elusive. Here we show that a nuclease toxin in Myxococcus xanthus requires multiple proteins to assemble into a complex for toxin delivery. These proteins, all encoded within the toxin-gene cluster, include a bifunctional immunity protein, an adaptor, a proline-isoleucine-proline-tyrosine family protein, and three co-chaperones. The formed complex escorts the toxin protein to the secretion apparatus, being recruited through the binding of VgrG to the proline-isoleucine-proline-tyrosine protein of the complex. We show that the proline-isoleucine-proline-tyrosine and toxin proteins are propelled out of the cell by the secretion system, while the other complex proteins are retained inside. This pre-secretion toxin-delivery process provides potential for functional versatility of the type VI secretion systems and the toxin-immunity systems. We investigate how a distantly encoded Myxococcus xanthus toxin is prepared for type VI secretion. A multichaperone presecretion assembly links the toxin to a PIPY protein that recruits it to the secretion spike.