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The widespread use of topical antibiotics enriches for resistance in Staphylococcus aureus isolated from Atopic Dermatitis patients

ABSTRACT: The widespread use of topical antibiotics enriches for resistance in Staphylococcus aureus isolated from Atopic Dermatitis patients

PROVIDER: PRJEB25052 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR2309520_1.fastq.gz	Fastqsanger.gz
	ERR2309520_2.fastq.gz	Fastqsanger.gz
	ERR2309530_1.fastq.gz	Fastqsanger.gz
	ERR2309530_2.fastq.gz	Fastqsanger.gz
	ERR2309540_1.fastq.gz	Fastqsanger.gz

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The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from patients with atopic dermatitis.

Project description:BACKGROUND:Carriage rates of Staphylococcus aureus on affected skin in atopic dermatitis (AD) are approximately 70%. Increasing disease severity during flares and overall disease severity correlate with increased burden of S. aureus. Treatment in AD therefore often targets S. aureus with topical and systemic antimicrobials. OBJECTIVES:To determine whether antimicrobial sensitivities and genetic determinants of resistance differed in S. aureus isolates from the skin of children with AD and healthy child nasal carriers. METHODS:In this case-control study, we compared S. aureus isolates from children with AD (n = 50) attending a hospital dermatology department against nasal carriage isolates from children without skin disease (n = 49) attending a hospital emergency department for noninfective conditions. Using whole genome sequencing we generated a phylogenetic framework for the isolates based on variation in the core genome, then compared antimicrobial resistance phenotypes and genotypes between disease groups. RESULTS:Staphylococcus aureus from cases and controls had on average similar numbers of phenotypic resistances per isolate. Case isolates differed in their resistance patterns, with fusidic acid resistance (FusR ) being significantly more frequent in AD (P = 0·009). The genetic basis of FusR also differentiated the populations, with chromosomal mutations in fusA predominating in AD (P = 0·049). Analysis revealed that FusR evolved multiple times and via multiple mechanism in the population. Carriage of plasmid-derived qac genes, which have been associated with reduced susceptibility to antiseptics, was eight times more frequent in AD (P = 0·016). CONCLUSIONS:The results suggest that strong selective pressure drives the emergence and maintenance of specific resistances in AD.

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Effect of topical emollient on the development of atopic dermatitis and atopic march in a mice model

Project description:To investigate the effect of emollient on atopic march in a murine model of chronic atopic dermatitis (AD). Mice were divided into 3 groups and treated with topical calcipotriol and ovalbumin alone or with a linoleic acid-ceramide-containing emollient. After 28 days, clinical, histological, and transcriptomic analyses were performed in skin lesions, lung and serum. Calcipotriol combined with ovalbumin induced a typical AD model with concomitant increased expression of Th2 and basophil-related genes in the lung. Compared to AD group, emollient group: 1) Skin: clinical severity and inflammatory cell infiltration were significantly reduced and transcriptomic analysis revealed significant downregulation of AD-related genes (286 of 1450 differentially expressed genes (DEGs)) including those related to innate inflammation (S100a8/a9, Il1b, Defb3/6, Mmp12), chemokines (Cxcl1/3, Ccl3/4) and barrier (Krt2/6b/80, Serpinb12, Lce3e, Sprr2). DEGs down-regulated by emollient were enriched in mitochondrial OXPHOS-related pathways, while up-regulated DEGs were mainly enriched in axon guidance, tight junctions, as shown by KEGG analyses. 2) Serum: total IgE and TSLP levels were significantly decreased, and IL-4 levels showed a decreasing tendency. 3) Lung: 187 of 275 upregulated DEGs were significantly downregulated in lung tissue including genes involved in cytokine and cytokine receptor interaction (Cxcl2/Cxcr2, Ccl2/3, Csf3r, etc.) and basophil activation (Mcpt8, Cd200r3, Ms4a2). Thus, topical emollient not only reduces skin inflammation and maintain skin barrier homeostasis by inhibiting the mitochondrial respiratory chain, but also limits systemic inflammation by decreasing TSLP and IgE levels. Moreover, it reduces respiratory chemokine production and basophil infiltration and activation, providing a molecular basis for blocking the atopic march.

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A Phase 1b Randomized Single-Center Trial of Topical Cerdulatinib (DMVT-502) in Patients with Mild-to-Moderate Atopic Dermatitis

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Effect of topical emollient on the development of atopic dermatitis and atopic march in a mice model

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Gene expression data from atopic dermatitis induced NC/Nga mouse model skin

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TWEAK Upregulates atopic dermatitis related genes

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