Daptomycin resistance mechanisms in clinically derived Staphylococcus aureus strains assessed by a combined transcriptomics and proteomics approach

Fischer, Adrien; Yang, Soo-Jin; Bayer, Arnold S.; Vaezzadeh, Ali R.; Herzig, Sébastien; Stenz, Ludwig; Girard, Myriam; Sakoulas, George; Scherl, Alexander; Yeaman, Michael R.; Proctor, Richard A.; Schrenzel, Jacques; François, Patrice

doi:10.1093/jac/dkr195

Cited by 91 publications

(92 citation statements)

References 97 publications

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“…98,[102][103][104][105][106] The dlt operon is involved in the incorporation of D-alanine into cell wall teichoic acids. The alanylation of these surface-exposed structures results in an increase in the net positive charge of the cell surface, which may affect daptomycin's ability to function in the same manner as PG lysylation.…”

Section: Cell Wall Permeabilitymentioning

confidence: 99%

The action mechanism of daptomycin

Taylor

Palmer

2016

Bioorganic & Medicinal Chemistry

208

167

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Daptomycin is a lipopeptide antibiotic produced by the soil bacterium Streptomyces roseosporus that is clinically used to treat severe infections with Grampositive bacteria. In this review, we discuss the mode of action of this important antibiotic. Although daptomycin is structurally related to amphomycin and similar lipopeptides that inhibit peptidoglycan biosynthesis, experimental studies have not produced clear evidence that daptomycin shares their action mechanism. Instead, the best characterized effect of daptomycin is the permeabilization and depolarization of the bacterial cell membrane. This activity, which can account for daptomycin's bactericidal effect, correlates with the level of phosphatidylglycerol (PG) in the membrane. Accordingly, reduced synthesis of PG or its increased conversion to lysyl-PG promotes bacterial resistance to daptomycin. While other resistance mechanisms suggest that daptomycin may indeed directly interfere with cell wall synthesis or cell division, such effects still await direct experimental confirmation. Daptomycin's complex structure and biosynthesis have hampered the analysis of its structure activity relationships. Novel methods of total synthesis, including a recent one that is carried out entirely on a solid phase, will enable a more thorough and systematic exploration of the sequence space.

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Section: Cell Wall Permeabilitymentioning

confidence: 99%

The action mechanism of daptomycin

Taylor

Palmer

2016

Bioorganic & Medicinal Chemistry

208

167

View full text Add to dashboard Cite

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“…Its in vivo activity against enterococci is still debatable (Canton et al, 2010). Daptomycin resistance developed under www.intechopen.com therapy in bacteria other than enterococci and was multifactorial and is still not understood completely (Fischer et al, 2011).…”

Section: Daptomycin Resistancementioning

confidence: 99%

Current Trends of Emergence and Spread of Vancomycin-Resistant Enterococci

Werner¹

2012

Antibiotic Resistant Bacteria - A Continuous Challenge in the New Millennium

182

228

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“…S. aureus nonsusceptibility to daptomycin is multifactorial, the pathway of which appears to be isolate specific, involving alterations to both the cell membrane and the cell wall via adaptations in metabolic function and stress response regulatory pathways (93). Recently, whole-genome sequencing was performed on a collection of clinical daptomycin-susceptible S. aureus strains and their isogenic daptomycin-NS daughter strains, isolated from nine patients who had failed daptomycin therapy (94).…”

Section: Daptomycin Nonsusceptibility In Staphylococcus Aureusmentioning

confidence: 99%

A Current Perspective on Daptomycin for the Clinical Microbiologist

2013

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SUMMARY Daptomycin is a lipopeptide antimicrobial with in vitro bactericidal activity against Gram-positive bacteria that was first approved for clinical use in 2004 in the United States. Since this time, significant data have emerged regarding the use of daptomycin for the treatment of serious infections, such as bacteremia and endocarditis, caused by Gram-positive pathogens. However, there are also increasing reports of daptomycin nonsusceptibility, in Staphylococcus aureus and, in particular, Enterococcus faecium and Enterococcus faecalis . Such nonsusceptibility is largely in the context of prolonged treatment courses and infections with high bacterial burdens, but it may occur in the absence of prior daptomycin exposure. Nonsusceptibility in both S. aureus and Enterococcus is mediated by adaptations to cell wall homeostasis and membrane phospholipid metabolism. This review summarizes the data on daptomycin, including daptomycin's unique mode of action and spectrum of activity and mechanisms for nonsusceptibility in key pathogens, including S. aureus , E. faecium , and E. faecalis . The challenges faced by the clinical laboratory in obtaining accurate susceptibility results and reporting daptomycin MICs are also discussed.

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Daptomycin resistance mechanisms in clinically derived Staphylococcus aureus strains assessed by a combined transcriptomics and proteomics approach

Abstract: Compatible with previous in vitro observations, in vivo-acquired DAP(R) in S. aureus is a complex, multistep phenomenon involving: (i) strain-dependent phenotypes; (ii) transcriptome adaptation; and (iii) modification of the lipid and protein contents of cellular envelopes.

Cited by 91 publications

References 97 publications

The action mechanism of daptomycin

The action mechanism of daptomycin

Current Trends of Emergence and Spread of Vancomycin-Resistant Enterococci

A Current Perspective on Daptomycin for the Clinical Microbiologist

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