Single-cell approach dissectingagrquorum sensing dynamics inStaphylococcus aureus

Abstract

AbstractStaphylococcus aureusboth colonizes humans and causes severe virulent infections. Virulence is regulated by theagrquorum sensing system and its autoinducing peptide (AIP), with dynamics at the single-cell level across fouragr-types – each defined by distinct AIP sequences and capable of cross-inhibition – remaining elusive. Employing microfluidics, time-lapse microscopy, and deep-learning image analysis, we uncovered significant differences in AIP sensitivity amongagr-types. We observed bimodalagractivation, attributed to intergenerational phenotypic stability and influenced by AIP concentration. Upon AIP stimulation,agr-IIIshowed AIP insensitivity, whileagr-IIexhibited increased sensitivity and prolonged generation time. Beyond expected cross-inhibition ofagr-Iby heterologous AIP-II and -III, the presumably cross-activating AIP-IV also inhibitedagr-I. Community interactions across differentagr-type pairings revealed four main patterns: stable or switched dominance, and delayed or stable dual activation, influenced by community characteristics. These insights underscore the potential of personalized treatment strategies considering virulence and genetic diversity.