1.A.150.  The Virulence-associated Protein A/B (VapA/B) Family 

Pathogenic Rhodococcus (Pathogenic Rhodococcus equi releases the virulence-associated protein A (VapA) within macrophage phagosomes (Nehls et al. 2024). VapA permeabilizes phagosome and lysosome membranes and reduces acidification of both compartments. VapA interacts with model membranes in four steps: (i) binding with a change of mechanical properties, (ii) formation of specific membrane domains, (iii) permeabilization within the domains, and (iv) pH-specific transformation of domains. VapA binds to membranes in one step at pH 6.5 and in two steps at pH 4.5 and decreases membrane fluidity. VapA increased the surface heterogeneity of liquid disordered domains. Furthermore, VapA led to the formation of a new microstructured domain type and, at pH 4.5, to the formation of 5 nm high domains. VapA binding, its integration and lipid domain formation depended on lipid composition, pH, protein concentration and lateral membrane pressure. VapA-mediated permeabilization is clearly distinct from that caused by classical microbial pore formers and contributes to the multiplication of Rhodococcus equi in phagosome (Nehls et al. 2024).