Abstract
Invasive infection by the Gram-positive pathogen Staphylococcus aureus is controlled by a four gene operon, agr that encodes a quorum sensing system for the regulation of virulence. While agr has been well studied in S. aureus, the contribution of agr homologues and analogues in other Gram-positive pathogens is just beginning to be understood. Intriguingly, other significant human pathogens, including Clostridium perfringens, Listeria monocytogenes, and Enterococcus faecalis contain agr or analogues linked to virulence. Moreover, other significant human Gram-positive pathogens use peptide based quorum sensing systems to establish or maintain infection. The potential for commonality in aspects of these signaling systems across different species raises the prospect of identifying therapeutics that could target multiple pathogens. Here, we review the status of research into these agr homologues, analogues, and other peptide based quorum sensing systems in Gram-positive pathogens as well as the potential for identifying common pathways and signaling mechanisms for therapeutic discovery.
Highlights
IntroductionThe contribution of communication systems within human bacterial pathogens to gene regulation has significantly altered our comprehension of how pathogens adapt to specific niches to promote disease
This exquisite sensitivity may serve as a defense mechanism for S. aureus, as we have previously shown that a single cell enclosed in a small space, such as the phagosome of a macrophage, can secrete sufficient auto-inducing peptide pheromone (AIP) within a short time to trigger the agr-mediated quorum sensing (QS)
Listeria monocytogenes is the etiologic agent of listeriosis, a food-borne infection that causes a wide range of severe illnesses in the elderly, neonates and immunocompromised patients, and the agr operon assists this pathogen in persisting through harsh environments
Summary
The contribution of communication systems within human bacterial pathogens to gene regulation has significantly altered our comprehension of how pathogens adapt to specific niches to promote disease. Bacterial pathogens across the phylum of Firmicutes encode and express either homologues and analogues of the agr operon or similar QS systems that use small peptide “quormones” to regulate pathogenesis [18,19,20,21,22,23,24] (Table 1, see [25] for a description of the Quorumpeps database, available at http://quorumpeps.ugent.be, which provides multiple tools for investigating peptide quormones) Together these observations hint at the potential for development of anti-virulence compounds that are efficacious in numerous G+ pathogens.
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