Relationship between vancomycin tolerance and clinical outcomes in<i>Staphylococcus aureus</i>bacteraemia

Britt, Nicholas S.; Patel, Nimish; Shireman, Theresa I.; Atrouni, Wissam I. El; Horvat, Rebecca T.; Steed, Molly E.

doi:10.1093/jac/dkw453

Cited by 23 publications

(15 citation statements)

References 39 publications

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“…Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the major multidrug-resistant pathogens responsible for severe infections with high mortality rates ( Stefani et al, 2015 ; Yoon et al, 2016 ; Britt et al, 2017 ). The subset of daptomycin-resistant (DAP R ) S. aureus is of particular concern for the cumulative non-reversible metabolic changes demonstrated in resistant strains and for the difficulty in the treatment of severe infections ( Bayer et al, 2013 ; Reed et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Genomic and Long-Term Transcriptomic Imprints Related to the Daptomycin Mechanism of Action Occurring in Daptomycin- and Methicillin-Resistant Staphylococcus aureus Under Daptomycin Exposure

et al. 2020

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Daptomycin (DAP) is one of the last-resort treatments for heterogeneous vancomycinintermediate Staphylococcus aureus (hVISA) and vancomycin-intermediate S. aureus (VISA) infections. DAP resistance (DAP-R) is multifactorial and mainly related to cellenvelope modifications caused by single-nucleotide polymorphisms and/or modulation mechanisms of transcription emerging as result of a self-defense process in response to DAP exposure. Nevertheless, the role of these adaptations remains unclear. We aim to investigate the comparative genomics and late post-exponential growthphase transcriptomics of two DAP-resistant/DAP-susceptible (DAP R/S) methicillinresistant S. aureus (MRSA) clinical strain pairs to focalize the genomic and longterm transcriptomic fingerprinting and adaptations related to the DAP mechanism of action acquired in vivo under DAP pressure using Illumina whole-genome sequencing (WGS), RNA-seq, bioinformatics, and real-time qPCR validation. Comparative genomics revealed that membrane protein and transcriptional regulator coding genes emerged as shared functional coding-gene clusters harboring mutational events related to the DAP-R onset in a strain-dependent manner. Pairwise transcriptomic enrichment analysis highlighted common and strain pair-dependent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, whereas DAP R/S double-pair cross-filtering returned 53 differentially expressed genes (DEGs). A multifactorial long-term transcriptomic-network characterized DAP R MRSA includes alterations in (i) peptidoglycan biosynthesis, cell division, and cell-membrane (CM) organization genes, as well as a cidB/lytS autolysin genes; (ii) ldh2 involved in fermentative metabolism; (iii) CM-potential perturbation genes; and (iv) oxidative and heat/cold stress response-related genes. Moreover, a D-alanyl-D-alanine decrease in cell-wall muropeptide characterized DAP/glycopeptide

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Section: Introductionmentioning

confidence: 99%

Genomic and Long-Term Transcriptomic Imprints Related to the Daptomycin Mechanism of Action Occurring in Daptomycin- and Methicillin-Resistant Staphylococcus aureus Under Daptomycin Exposure

et al. 2020

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“…Vancomycin and ticlonin have been demonstrated. Vancomycin lacked bactericidal activity (defined as an MBC/MIC ratio of > or = 32) against two methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with bone and joint infection [21,22]. By contrast, MIC values of many strains were consistent with the tolerance in literature reported (MBC/MIC ratios ≥ 32) [23].…”

Section: Methodsmentioning

confidence: 91%

Neo-5,22E-Cholestadienol Derivatives from Buthus martensii Karsch and Targeted Bactericidal Action Mechanisms

Yin

Gao

et al. 2018

Molecules

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The discovery and search for new antimicrobial molecules from insects and animals that live in polluted environments is a very important step in the scientific search for solutions to the current problem of antibiotic resistance. Previously, we have reported that the secondary metabolite with the antibacterial action discovered in scorpion. The current study further isolated three new compounds from Buthus martensii karsch, while compounds 1 and 2 possessed 5,22E-cholestadienol derivatives whose structure demonstrated broad spectrum bactericide activities. To explore the antibacterial properties of these new compounds, the result shows that compound 2 inhibited bacterial growth of both S. aureus and P. aeruginosa in a bactericidal rather than a bacteriostatic manner (MBC/MIC ratio ≤ 2). Similarly, with compound 1, a ratio of MBC/MIC ≤ 2 indicates bactericidal activity inhibited bacterial growth of P. aeruginosa. Remarkably, this suggests that two compounds can be classified as bactericidal agents against broad spectrum bactericide activities for 5,22E-cholestadienol derivatives from Buthus martensii karsch. The structures of compounds 1–3 were established by comprehensive spectra analysis including two-dimensional nuclear magnetic resonance (2D-NMR) and high-resolution electrospray ionization-mass spectrometry (HRESI-MS) spectra. The antibacterial mechanism is the specific binding (various of bonding forces between molecules) using compound 1 or 2 as a ligand based on the different receptor proteins’—2XRL or 1Q23—active sites from bacterial ribosome unit A, and thus prevent the synthesis of bacterial proteins. This unique mechanism avoids the cross-resistance issues of other antibacterial drugs.

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“…Antimicrobial tolerance is associated with persistent MRSA endovascular infection and poor clinical outcome [3]. While changes in multiple genes can contribute to enhanced tolerance in staphylococci [10], the associated pathways typically converge on purine biosynthesis [11,12] and the stringent response [6].…”

Section: Discussionmentioning

confidence: 99%

“…Clinicians have long recognized the role of antibiotic resistance in treatment failures [2]. Over the past decade, it has become clear that antibiotic tolerance can also contribute to unfavorable clinical outcomes [3]. Antimicrobial tolerance occurs when a small fraction of a bacterial population ceases to focus on cell division and shifts to an alternate metabolic program favoring small molecule synthesis over growth [4,5].…”

Section: Introductionmentioning

confidence: 99%

Distinct Effectiveness of Oritavancin against Tolerance-Induced Staphylococcus aureus

2020

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Within a sufficiently large bacterial population, some members will naturally adopt an alternate, metabolically-active state that favors small molecule synthesis over cell division. These isogenic “tolerant” subpopulations have variable responses during antibiotic exposure and can remain viable in the presence of typically bactericidal concentrations. In this study, we determine the ability of typical and atypical antistaphylococcal therapies to reduce the viability of mupirocin-induced tolerant Staphylococcus aureus bacteria. Overall, tolerance-induced staphylococci exhibited a markedly decreased rate and extent of killing following antibiotic exposure. However, oritavancin remained effective at maintaining a similar extent of killing. Further studies to investigate the role of oritavancin against recurrent or relapse staphylococcal infection are warranted.

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Relationship between vancomycin tolerance and clinical outcomes inStaphylococcus aureusbacteraemia

Cited by 23 publications

References 39 publications

Genomic and Long-Term Transcriptomic Imprints Related to the Daptomycin Mechanism of Action Occurring in Daptomycin- and Methicillin-Resistant Staphylococcus aureus Under Daptomycin Exposure

Genomic and Long-Term Transcriptomic Imprints Related to the Daptomycin Mechanism of Action Occurring in Daptomycin- and Methicillin-Resistant Staphylococcus aureus Under Daptomycin Exposure

Neo-5,22E-Cholestadienol Derivatives from Buthus martensii Karsch and Targeted Bactericidal Action Mechanisms

Distinct Effectiveness of Oritavancin against Tolerance-Induced Staphylococcus aureus

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