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Antimicrobials

Persisters come under fire

Nature Reviews Microbiology volume 12, page 3 (2014)Cite this article

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The compound acyldepsipeptide (ADEP) from Streptomyces hawaiiensis kills growing cells by triggering the activation of ClpP, which leads to uncontrolled proteolysis of nascent peptides and eventual cell death. Conlon et al. reasoned that extended incubation with a more potent ADEP derivative, ADEP4, might activate ClpP in dormant persisters and lead to nonspecific degradation of mature proteins. Thus, the authors compared the proteomes of stationary phase Staphylococcus aureus populations with and without ADEP4 treatment and found that the addition of ADEP4 resulted in the degradation of more than 400 proteins. This result indicates that ClpP becomes a nonspecific protease in the presence of ADEP4 and causes uncontrolled proteolysis in non-replicating cells.

the combination of ADEP4 and rifampicin results in complete eradication of S. aureus biofilms in vitro and in a deep-seated chronic infection in a mouse model

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References

  1. Conlon, B. P. et al. Activated ClpP kills persisters and eradicates a chronic biofilm infection. Nature http://dx.doi.org/10.1038/nature12790 (2013)

  2. Kim, J.- H. et al. A genetic strategy to identify targets for the development of drugs that prevent bacterial persistence. Proc. Natl Acad. Sci. USA http://dx.doi.org/10.1073/pnas.1315860110 (2013)

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Authors
  1. Christina Tobin Kåhrström
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Balaban, N. Q. et al. A problem of persistence: still more questions than answers? Nature Rev. Microbiol. 11, 587–591 (2013)

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Kåhrström, C. Persisters come under fire. Nat Rev Microbiol 12, 3 (2014). https://doi.org/10.1038/nrmicro3181

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