MroQ Is a Novel Abi-Domain Protein That Influences Virulence Gene Expression in via Modulation of Agr Activity.

Numerous factors have, to date, been identified as playing a role in the regulation of Agr activity in , including transcription factors, antisense RNAs, and host elements. Herein we investigated the product of SAUSA300_1984 (termed MroQ), a transmembrane Abi-domain/M79 protease-family protein, as a novel effector of this system. Using a USA300 mutant, we observed a drastic reduction in proteolysis, hemolysis, and pigmentation that was fully complementable. This appears to result from diminished activity, as transcriptional analysis revealed significant decreases in expression of both RNAII and RNAIII in the mutant. Such effects appear to be direct, rather than indirect, as known effectors demonstrated limited alterations in their activity upon disruption. A comparison of RNA sequencing data sets for both and mutants revealed a profound overlap in their regulomes, with the majority of factors affected being known virulence determinants. Importantly, the preponderance of alterations in expression were more striking in the mutant, indicating that MroQ is necessary, but not sufficient, for Agr function. Mechanism profiling revealed that putative residues for metalloprotease activity within MroQ are required for its Agr-controlling effect; however, this was not wielded at the level of AgrD processing. Virulence assessment demonstrated that both and mutants exhibited increased formation of renal abscesses but decreased skin abscess formation alongside diminished dermonecrosis. Collectively, we present the characterization of a novel effector in which would appear to be a direct regulator, potentially functioning via interaction with the AgrC histidine kinase.