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Beyond killing: Can we find new ways to manage infection?

Vale PF, McNally L, Doeschl-Wilson A, King KC, Popat R, Domingo-Sananes MR, Allen JE, Soares MP, Kümmerli R - Evol Med Public Health (2016)

Bottom Line: An efficient strategy to stay ahead of rapidly adapting pathogens should include approaches that replace, complement or enhance the effect of both current and novel antimicrobial compounds.We discuss the therapeutic potential of these approaches and examine their possible consequences for pathogen evolution.To guarantee a longer half-life of these alternatives to directly killing pathogens, and to gain a full understanding of their population-level consequences, we encourage future work to incorporate evolutionary perspectives into the development of these treatments.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immunity, Infection and Evolution Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK pedro.vale@ed.ac.uk.

No MeSH data available.


Related in: MedlinePlus

Examples of anti-virulence approaches. (A) In a classical infection, bacteria adhere to host tissue using their flagella and pilli. They then secrete quorum-sensing molecules (red dots) to communicate with nearby cells in order to coordinate the secretion of harmful virulence factors (green pentagons), such as toxins and tissue-degrading enzymes. (B) A potent anti-virulence approach is to prevent bacterial adhesion by the administration of hydrophilic compounds (purple layer) [15]. (C) Interference with bacterial communication, called quorum-quenching has been proposed as another efficient way to control bacterial infections. Numerous drugs (yellow half-circles) have been shown to either quench the bacterial signals outside the cell or to directly stall signal production within cells [26], (D) Approaches have also been developed to target the damaging virulence factors (e.g. siderophores, toxins) directly by either suppressing their synthesis or by inhibiting their actions once secreted [12]
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eow012-F1: Examples of anti-virulence approaches. (A) In a classical infection, bacteria adhere to host tissue using their flagella and pilli. They then secrete quorum-sensing molecules (red dots) to communicate with nearby cells in order to coordinate the secretion of harmful virulence factors (green pentagons), such as toxins and tissue-degrading enzymes. (B) A potent anti-virulence approach is to prevent bacterial adhesion by the administration of hydrophilic compounds (purple layer) [15]. (C) Interference with bacterial communication, called quorum-quenching has been proposed as another efficient way to control bacterial infections. Numerous drugs (yellow half-circles) have been shown to either quench the bacterial signals outside the cell or to directly stall signal production within cells [26], (D) Approaches have also been developed to target the damaging virulence factors (e.g. siderophores, toxins) directly by either suppressing their synthesis or by inhibiting their actions once secreted [12]

Mentions: One promising alternative to classic antibiotics is to focus on strategies reducing pathogen virulence, which we define in the broadest sense as the degree of pathology and overall disease symptoms experienced during infection. Pathogen virulence can be targeted at least at three levels (Fig. 1) [12–14], by interfering with: (i) pathogen adhesion, which is important for host invasion and colonization; (ii) quorum sensing, a cell-to-cell signalling system used by bacteria to coordinate the secretion of virulence factors; and (iii) expression and activity of virulence factors, which are usually secreted proteins or secondary metabolites that act directly or indirectly to cause tissue dysfunction and/or damage [9, 12]. Approaches belonging to these categories are called anti-virulence therapies, as they deprive essential virulence factors from infections without directly killing the pathogens themselves.Figure 1.


Beyond killing: Can we find new ways to manage infection?

Vale PF, McNally L, Doeschl-Wilson A, King KC, Popat R, Domingo-Sananes MR, Allen JE, Soares MP, Kümmerli R - Evol Med Public Health (2016)

Examples of anti-virulence approaches. (A) In a classical infection, bacteria adhere to host tissue using their flagella and pilli. They then secrete quorum-sensing molecules (red dots) to communicate with nearby cells in order to coordinate the secretion of harmful virulence factors (green pentagons), such as toxins and tissue-degrading enzymes. (B) A potent anti-virulence approach is to prevent bacterial adhesion by the administration of hydrophilic compounds (purple layer) [15]. (C) Interference with bacterial communication, called quorum-quenching has been proposed as another efficient way to control bacterial infections. Numerous drugs (yellow half-circles) have been shown to either quench the bacterial signals outside the cell or to directly stall signal production within cells [26], (D) Approaches have also been developed to target the damaging virulence factors (e.g. siderophores, toxins) directly by either suppressing their synthesis or by inhibiting their actions once secreted [12]
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4834974&req=5

eow012-F1: Examples of anti-virulence approaches. (A) In a classical infection, bacteria adhere to host tissue using their flagella and pilli. They then secrete quorum-sensing molecules (red dots) to communicate with nearby cells in order to coordinate the secretion of harmful virulence factors (green pentagons), such as toxins and tissue-degrading enzymes. (B) A potent anti-virulence approach is to prevent bacterial adhesion by the administration of hydrophilic compounds (purple layer) [15]. (C) Interference with bacterial communication, called quorum-quenching has been proposed as another efficient way to control bacterial infections. Numerous drugs (yellow half-circles) have been shown to either quench the bacterial signals outside the cell or to directly stall signal production within cells [26], (D) Approaches have also been developed to target the damaging virulence factors (e.g. siderophores, toxins) directly by either suppressing their synthesis or by inhibiting their actions once secreted [12]
Mentions: One promising alternative to classic antibiotics is to focus on strategies reducing pathogen virulence, which we define in the broadest sense as the degree of pathology and overall disease symptoms experienced during infection. Pathogen virulence can be targeted at least at three levels (Fig. 1) [12–14], by interfering with: (i) pathogen adhesion, which is important for host invasion and colonization; (ii) quorum sensing, a cell-to-cell signalling system used by bacteria to coordinate the secretion of virulence factors; and (iii) expression and activity of virulence factors, which are usually secreted proteins or secondary metabolites that act directly or indirectly to cause tissue dysfunction and/or damage [9, 12]. Approaches belonging to these categories are called anti-virulence therapies, as they deprive essential virulence factors from infections without directly killing the pathogens themselves.Figure 1.

Bottom Line: An efficient strategy to stay ahead of rapidly adapting pathogens should include approaches that replace, complement or enhance the effect of both current and novel antimicrobial compounds.We discuss the therapeutic potential of these approaches and examine their possible consequences for pathogen evolution.To guarantee a longer half-life of these alternatives to directly killing pathogens, and to gain a full understanding of their population-level consequences, we encourage future work to incorporate evolutionary perspectives into the development of these treatments.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immunity, Infection and Evolution Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK pedro.vale@ed.ac.uk.

No MeSH data available.


Related in: MedlinePlus