The chemoreceptor McpA mediates aerotaxis and redox taxis in Salmonella Typhimurium

Redox environments in nature are shaped by reactive oxygen species (ROS), oxygen, and metal ion chemistry, and exert profound effects on bacterial physiology and survival. In some pathogens, bacterial chemosensory zinc-binding (CZB) proteins mediate responses to inflammatory ROS that may contribute to pathogenesis, but their functions in the many environmental bacteria that also possess them remain unclear. Reports of attraction to hypochlorous acid (HOCl), repulsion from hydroperoxides (ROOH) and other ROS, and responsiveness to exogenous zinc have left unresolved whether CZBs distinguish individual effectors or reflect an underlying sensory logic. Here, using time-resolved video microscopy to directly visualize swimming and taxis behaviors, we show that the CZB-containing receptor McpA in Salmonella Typhimurium mediates attraction to O2 and biologically relevant concentrations of HOCl, H2O2, and organic hydroperoxides, three types of oxidants generated through the neutrophil oxidative burst. This identifies the CZB domain as a previously unrecognized sensory architecture for aerotaxis, distinct from, and possibly more widespread, than the FAD-dependent Aer and heme-dependent HemAT and Aer2 families. Although Zn2+ itself is not redox-active, we show that McpA-dependent taxis is controlled by Zn2+ availability and that exogenous OZn2 and ROS promote the formation of insoluble zinc precipitates, which may generate Zn2+ gradients sensed through the CZB domain. We propose these findings are consistent with a model in which CZBs use soluble, bioavailable Zn2+ as a secondary messenger for highly sensitive navigation of environmental redox landscapes.