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Review
doi: 10.1038/ismej.2015.84. Epub 2015 May 29.

Can resistance against quorum-sensing interference be selected?

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Review

Can resistance against quorum-sensing interference be selected?

Rodolfo García-Contreras et al. ISME J.2016 Jan.

Abstract

Quorum-sensing (QS) interference is a novel therapy to fight bacterial infections that, unlike conventional antibiotic treatments, is focused on reducing the damage caused by pathogens (virulence) rather than focused on inhibiting their growth. Given this ideal, it was predicted that this approach will be impervious to or at least much less prone to resistance in bacterial populations. However, recently, resistance mechanisms against well-characterized quorum quenchers (QQs) have been found in the laboratory as well as in clinical strains, demonstrating that the rise of resistance against these kinds of compounds is possible. Nevertheless, it has been argued that even if resistance mechanisms against QS interference exist, this fact does not guarantee that resistance will spread. In the present work, we discuss recent insights derived from the latest experiments to address this question. In addition, we explain how environmental conditions like the stress produced by the host immune system may influence the selection of resistance and eventually lead to the selection of QS interference-resistant bacteria in a clinical setting.

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Figures

Figure 1
Figure 1
(a) Bacterial growth on a private good (for example, adenosine) with metabolism that is tightly dependent on QS in the presence of a QS inhibitor. Cooperator represents the variant that is resistant to the quorum-sensing inhibitor and able to quorum sense (R), whereas QS represents the variant sensitive to the QS inhibitor and unable to utilize QS (S). Sequential number of cells represents progressive times: (1) initial R and S population; (2) after growth, the R proportion is enriched as it is the only variant that can utilize the private good. (b) Bacterial grown on a private or a public good in confined environments in the presence of a QS inhibitor. Sequential number of cells represents progressive times: (1) initial R and S proportion isolates in different compartmentalized environments; (2) only R can grow, as S needs to exploit R for growing. (c) Bacterial growth on a public good (for example, bovine serum albumin) in the presence of a QS inhibitor. Sequential number of cells represents progressive times: (1) initial R and S population; (2) after growth, the S proportion is enriched as it exploits the public goods that is produced by the R cells. (d) Bacterial growth on a public good in the presence of stress (for example, oxidative stress from host cells) and in the presence of a QS inhibitor. Sequential numbers represent progressive times: (1) initial R and S proportion; (2) oxidative stress is applied to the bacterial population (note that the stress could be due other factors); (3) as S is much more sensitive to stress, R is selected.
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