The Complex Relationship between Virulence and Antibiotic Resistance.
TLDR
Uncovering key genetic interactions between virulence and resistance in biofilm bacteria is essential to identifying new druggable targets, ultimately providing a drug discovery and development pathway to improve treatment options for chronic and recurring infection.Abstract:
Antibiotic resistance, prompted by the overuse of antimicrobial agents, may arise from a variety of mechanisms, particularly horizontal gene transfer of virulence and antibiotic resistance genes, which is often facilitated by biofilm formation. The importance of phenotypic changes seen in a biofilm, which lead to genotypic alterations, cannot be overstated. Irrespective of if the biofilm is single microbe or polymicrobial, bacteria, protected within a biofilm from the external environment, communicate through signal transduction pathways (e.g., quorum sensing or two-component systems), leading to global changes in gene expression, enhancing virulence, and expediting the acquisition of antibiotic resistance. Thus, one must examine a genetic change in virulence and resistance not only in the context of the biofilm but also as inextricably linked pathologies. Observationally, it is clear that increased virulence and the advent of antibiotic resistance often arise almost simultaneously; however, their genetic connection has been relatively ignored. Although the complexities of genetic regulation in a multispecies community may obscure a causative relationship, uncovering key genetic interactions between virulence and resistance in biofilm bacteria is essential to identifying new druggable targets, ultimately providing a drug discovery and development pathway to improve treatment options for chronic and recurring infection.read more
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References
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TL;DR: Improvements in understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.
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Quorum Sensing in Bacteria
TL;DR: The evolution of quorum sensing systems in bacteria could, therefore, have been one of the early steps in the development of multicellularity.
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Julian Davies,Dorothy Davies +1 more
TL;DR: A review of antibiotic resistance development over the past half-century can be found in this article, with the oft-restated conclusion that it is time to act and to restore the therapeutic applications of antibiotics.
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TL;DR: The features of biofilm infections are summarized, the emerging mechanisms of resistance are reviewed, and potential therapies are discussed.
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Mechanisms of biofilm resistance to antimicrobial agents
Thien-Fah Mah,George A. O'Toole +1 more
TL;DR: Owing to the heterogeneous nature of the biofilm, it is likely that there are multiple resistance mechanisms at work within a single community.