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bioRxiv · 10.1101/2024.02.27.582246

Single-cell approach dissecting agr quorum sensing dynamics in Staphylococcus aureus

Baer, J.·Charlton, S. G. V.·Tarnutzer, A.·Ugolini, G. S.·Secchi, E.·Zinkernagel, A. S.
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Abstract

Staphylococcus aureus both colonizes humans and causes severe virulent infections. Virulence is regulated by the agr quorum sensing system and its autoinducing peptide (AIP), with dynamics at the single-cell level across four agr-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 among agr-types. We observed bimodal agr activation, attributed to intergenerational phenotypic stability and influenced by AIP concentration. Upon AIP stimulation, agr-III showed AIP insensitivity, while agr-II exhibited increased sensitivity and prolonged generation time. Beyond expected cross-inhibition of agr-I by heterologous AIP-II and -III, the presumably cross-activating AIP-IV also inhibited agr-I. Community interactions across different agr-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.

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Baer, J., Charlton, S. G. V., Tarnutzer, A., Ugolini, G. S., Secchi, E., Zinkernagel, A. S.. 2024-02-27. Single-cell approach dissecting agr quorum sensing dynamics in Staphylococcus aureus. https://doi.org/10.1101/2024.02.27.582246

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