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Review
. 2016 Oct:33:91-96.
doi: 10.1016/j.mib.2016.07.002. Epub 2016 Jul 25.

Targeting cell membrane adaptation as a novel antimicrobial strategy

Truc T Tran  1 , William R Miller  1 , Yousif Shamoo  2 , Cesar A Arias  3
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Review

Targeting cell membrane adaptation as a novel antimicrobial strategy

Truc T Tran et al. Curr Opin Microbiol. 2016 Oct.

Abstract

Emergence of antibiotic resistance is an example of the incredible plasticity of bacteria to survive in all environments. The search for new antibiotics active against traditional targets is more challenging due not only to the lack of novel natural products to fulfill the current clinical needs against multidrug-resistant (MDR) bacteria, but also for the possible 'collateral' effects on the human microbiota. Thus, non-traditional approaches to combat MDR bacteria have been proposed. Here, we discuss the possibility of targeting the membrane response to the antibiotic attack (cell membrane adaptation) as a viable strategy to increase the activity of current antimicrobials, enhance the activity of the innate immune system and prevent development of resistance during therapy using the three-component regulatory system LiaFSR of enterococci as a model.

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Figures

Figure 1
Figure 1. Bacterial cell membrane adaptation via two-component signal transduction systems
Protection of cell membrane is of paramount importance for bacterial survival. Several mechanism to protect the cell membrane against environmental stressors (including antibiotics) are available. The participation of signal transduction systems (two-component regulatory systems) is one of the most important strategies to mediate the cell membrane adaptive response.
Figure 2
Figure 2. A model of LiaR inhibitors
Inhibiting the LiaR response regulator (green) would prevent the activation of the cell membrane adaptive response triggered by antibiotics targeting the cell envelope.
See this image and copyright information in PMC

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