Pseudomonas aeruginosa ExlA and Serratia marcescens ShlA trigger cadherin cleavage by promoting calcium influx and ADAM10 activation

Pore-forming toxins are potent virulence factors secreted by a large array of bacteria. here,we deciphered the action of exla from pseudomonas aeruginosa and shla from serratia marcescens on host cell-cell junctions. exla and shla are two members of a unique family of pore-forming toxins secreted by a two-component secretion system. bacteria secreting either toxin induced an exla- or shla-dependent rapid cleavage of e-cadherin and ve-cadherin in epithelial and endothelial cells,respectively. cadherin proteolysis was executed by adam10,a host cell transmembrane metalloprotease. adam10 activation is controlled in the host cell by cytosolic ca2+concentration. we show that ca2+influx,induced by exla or shla pore formation in the plasma membrane,triggered adam10 activation,thereby leading to cadherin cleavage. our data suggest that adam10 is not a cellular receptor for exla and shla,further confirming that adam10 activation occurred via ca2+signalling. in conclusion,exla- and shla-secreting bacteria subvert a regulation mechanism of adam10 to activate cadherin shedding,inducing intercellular junction rupture,cell rounding and loss of tissue barrier integrity. © 2017 reboud et al.