Abstract

Staphylococci are commensal bacteria that colonize the epithelial surfaces of humans and many other mammals. These bacteria can also attach to implanted medical devices and develop surface-associated biofilm communities that resist clearance by host defenses and available chemotherapies. These communities are often associated with persistent staphylococcal infections that place a tremendous burden on the healthcare system. Understanding the regulatory program that controls staphylococcal biofilm development, as well as the environmental conditions that modulate this program, has been a focal point of research in recent years. A central regulator controlling biofilm development is a peptide quorum-sensing system, also called the accessory gene regulator or agr system. In the opportunistic pathogen Staphylococcus aureus, the agr system controls production of exo-toxins and exo-enzymes essential for causing infections, and simultaneously, it modulates the ability of this pathogen to attach to surfaces and develop a biofilm, or to disperse from the biofilm state. In this review, we explore advances on the interconnections between the agr quorum-sensing system and biofilm mechanisms, and topics covered include recent findings on how different environmental conditions influence quorum sensing, the impact on biofilm development, and ongoing questions and challenges in the field. As our understanding of the quorum sensing and biofilm interconnection advances, there are growing opportunities to take advantage of this knowledge and develop therapeutic approaches to control staphylococcal infections.

Highlights

  • The fact that S. aureus can colonize without harming the host is somewhat surprising considering the depth of secreted virulence factors produced by this pathogen [3, 7, 8]

  • For the other three promoters, AgrA activates the expression of the P2 promoter for the agrBDCA operon (Fig. 1), leading to the autoinduction loop, and AgrA activates expression of transcripts for the ␣- and ␤-phenol-soluble modulins (PSMs) [16]

  • It is interesting to note that a study investigating the impact of serum on agr expression that failed to find reduced agr transcription [39] differed from the aforementioned studies [28, 29] in that the serum was inactivated by heating at 56 °C for 30 min before it was added to S. aureus cultures

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Summary

MINIREVIEW crossmark

Impact of Environmental Cues on Staphylococcal Quorum Sensing and Biofilm Development*. Horswill From the Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242. The agr system has been the target of multiple comprehensive reviews [10, 11, 23, 24], and for more details not covered the interested reader is referred to these articles In this minireview, we will focus on the variety of environmental cues that have been demonstrated to impact quorum signaling in the staphylococci. We will focus on the variety of environmental cues that have been demonstrated to impact quorum signaling in the staphylococci Many of these are cues that are found in the host during colonization or infection, such as the impact of serum proteins and reactive oxygen species on agr function. Some challenges to be overcome and future perspectives are included

Inhibit Inhibit Inhibit Inhibit Inhibit Inhibit or enhance
Impact of Environmental Cues on Quorum Sensing
Direct Action of Serum and ROS on agr Components
Impact of Miscellaneous Factors by Unknown Mechanisms
Quorum Sensing and Biofilm Interconnections
Challenges in the Field and Future Perspectives

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