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Review
. 2018 Apr 1;10(7):779-794.
doi: 10.4155/fmc-2017-0199. Epub 2018 Mar 23.

Strategies against methicillin-resistant Staphylococcus aureus persisters

Wooseong Kim  1 , Gabriel L Hendricks  1 , Katerina Tori  1 , Beth B Fuchs  1 , Eleftherios Mylonakis  1
Affiliations
Review

Strategies against methicillin-resistant Staphylococcus aureus persisters

Wooseong Kim et al. Future Med Chem. .

Abstract

Chronic Staphylococcus aureus infections are complicated by frequent relapses not only from the development of drug resistance to conventional antibiotics, but also through the formation of persister bacterial cells. Bacterial persisters are in a transient, metabolically inactive state, making conventional antibiotics that target essential cellular growth processes ineffective, resulting in high clinical failure rates of antibiotic chemotherapy. The development of new antibiotics against persistent S. aureus is an urgent issue. Over the last decade, new strategies to identify S. aureus persister-active compounds have been proposed. This review summarizes the proposed targets, antipersister compounds and innovative methods that may augment conventional antibiotics against S. aureus persisters. The reviewed antipersister strategies can be summarized as two broad categories; directly targeting growth-independent targets and potentiating existing, ineffective antibiotics by aiding uptake or accessibility.

Keywords: MRSA; antibiotics; drug discover; persisters.

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Conflict of interest statement

Financial & competing interests disclosure

This paper was partly supported by NIH grant P01 AI083214 to Mylonakis, Eleftherios. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Acyldepsipeptides kill MRSA persisters by deregulating the ClpP protease.
Structures of natural acyldepsipeptides and their synthetic analogs (A) and mode of action (B).
<b>Figure 2.</b>
Figure 2.. Membrane-active antimicrobials effective against MRSA persisters.
Structures of XF-13 and HT61 (A), and structuresand bioactivities of NH125 and its analogs (B). MBEC: Minimum biofilm eradication concentration; MIC: Minimum inhibitory concentration; HC50: The concentration at which 50% of erythrocytes are lysed.
<b>Figure 3.</b>
Figure 3.. Structures and antimicrobial activities of DNA-crosslinking antimicrobial-anticancer drugs.
ECK99: Effective concentration for killing over 99% of persister cells; MIC: Minimum inhibitory concentration.
<b>Figure 4.</b>
Figure 4.. Engineered existing antibiotics effectively kill bacterial persisters.
Structures and functional mechanisms of pentobra (A), antibody-antibiotic conjugate (B), and kanamycin-peptide conjugate (C).
See this image and copyright information in PMC

References

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    2. •• Provides an excellent review of the biological properties of persisters and mechanism of persister formation.

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