Antagonistic effects of actin-specific toxins onSalmonellaTyphimurium invasion into mammalian cells

Abstract

Competition between bacterial species is a major factor shaping microbial communities. In this work, we explored the hypothesis that competition between bacterial pathogens can be mediated through antagonistic effects of bacterial effector proteins on host systems, particularly the actin cytoskeleton. UsingSalmonellaTyphimurium invasion into cells as a model, we demonstrate that invasion is inhibited if the host actin cytoskeleton is disturbed by any of the four tested actin-specific toxins:Vibrio choleraeMARTX actin crosslinking and Rho GTPase inactivation domains (ACD and RID, respectively), TccC3 fromPhotorhabdus luminescens, andSalmonella’sown SpvB. We noticed that ACD, being an effective inhibitor of tandem G-actin binding assembly factors, is likely to inhibit the activity of anotherVibrioeffector, VopF. In reconstituted actin polymerization assays confirmed by live-cell microscopy, we confirmed that ACD potently halted the actin nucleation and pointed-end elongation activities of VopF, revealing competition between these twoV. choleraeeffectors. Together, the results suggest bacterial effectors from different species that target the same host machinery or proteins may represent an effective but largely overlooked mechanism of indirect bacterial competition in host-associated microbial communities. Whether the proposed inhibition mechanism involves the actin cytoskeleton or other host cell compartments, such inhibition deserves investigation and may contribute to a documented scarcity of human enteric co-infections by different pathogenic bacteria.