<i>Staphylococcus aureus</i> Biofilm-Associated Infections: Have We Found a Clinically Relevant Target?

<i>Staphylococcus aureus</i> is one of the most diverse bacterial pathogens. This is reflected in its ability to cause a wide array of infections and in genotypic and phenotypic differences between clinical isolates that extend beyond their antibiotic resistance status. Many <i>S....

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Bibliographic Details
Main Authors: Karen E. Beenken, Mark S. Smeltzer
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/13/4/852
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Summary:<i>Staphylococcus aureus</i> is one of the most diverse bacterial pathogens. This is reflected in its ability to cause a wide array of infections and in genotypic and phenotypic differences between clinical isolates that extend beyond their antibiotic resistance status. Many <i>S. aureus</i> infections, including those involving indwelling medical devices, are therapeutically defined by the formation of a biofilm. This is reflected in the number of reports focusing on <i>S. aureus</i> biofilm formation and biofilm-associated infections. These infections are characterized by a level of intrinsic resistance that compromises conventional antibiotic therapy irrespective of acquired resistance, suggesting that an inhibitor of biofilm formation would have tremendous clinical value. Many reports have described large-scale screens aimed at identifying compounds that limit <i>S. aureus</i> biofilm formation, but relatively few examined whether the limitation was sufficient to overcome this intrinsic resistance. Similarly, while many of these reports examined the impact of putative inhibitors on <i>S. aureus</i> phenotypes, very few took a focused approach to identify and optimize an effective inhibitor of specific biofilm-associated targets. Such approaches are dependent on validating a target, hopefully one that is not restricted by the diversity of <i>S. aureus</i> as a bacterial pathogen. Rigorous biological validation of such a target would allow investigators to virtually screen vast chemical libraries to identify potential inhibitors that warrant further investigation based on their predicted function. Here, we summarize reports describing <i>S. aureus</i> regulatory loci implicated in biofilm formation to assess whether they are viable targets for the development of an anti-biofilm therapeutic strategy with an emphasis on whether <i>sarA</i> has been sufficiently validated to warrant consideration in this important clinical context.
ISSN:2076-2607