Dataset Information

Clonal Emergence of Invasive Multidrug-Resistant Staphylococcus epidermidis Deconvoluted via a Combination of Whole-Genome Sequencing and Microbiome Analyses.

ABSTRACT: Background:Pathobionts, bacteria that are typically human commensals but can cause disease, contribute significantly to antimicrobial resistance. Staphylococcus epidermidis is a prototypical pathobiont as it is a ubiquitous human commensal but also a leading cause of healthcare-associated bacteremia. We sought to determine the etiology of a recent increase in invasive S. epidermidis isolates resistant to linezolid. Methods:Whole-genome sequencing (WGS) was performed on 176 S. epidermidis bloodstream isolates collected at the MD Anderson Cancer Center in Houston, Texas, between 2013 and 2016. Molecular relationships were assessed via complementary phylogenomic approaches. Abundance of the linezolid resistance determinant cfr was determined in stool samples via reverse-transcription quantitative polymerase chain reaction. Results:Thirty-nine of the 176 strains were linezolid resistant (22%). Thirty-one of the 39 linezolid-resistant S. epidermidis infections were caused by a particular clone resistant to multiple antimicrobials that spread among leukemia patients and carried cfr on a 49-kb plasmid (herein called pMB151a). The 6 kb of pMB151a surrounding the cfr gene was nearly 100% identical to a cfr-containing plasmid isolated from livestock-associated staphylococci in China. Analysis of serial stool samples from leukemia patients revealed progressive staphylococcal domination of the intestinal microflora and an increase in cfr abundance following linezolid use. Conclusions:The combination of linezolid use plus transmission of a multidrug-resistant clone drove expansion of invasive, linezolid-resistant S. epidermidis. Our results lend support to the notion that a combination of antibiotic stewardship plus infection control measures may help to control the spread of a multidrug-resistant pathobiont.

SUBMITTER: Li X

PROVIDER: S-EPMC6051468 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Clonal Emergence of Invasive Multidrug-Resistant Staphylococcus epidermidis Deconvoluted via a Combination of Whole-Genome Sequencing and Microbiome Analyses.

Li Xiqi X Arias Cesar A CA Aitken Samuel L SL Galloway Peña Jessica J Panesso Diana D Chang Michael M Diaz Lorena L Rios Rafael R Numan Yazan Y Ghaoui Sammi S DebRoy Sruti S Bhatti Micah M MM Simmons Dawn E DE Raad Isaam I Hachem Ray R Folan Stephanie A SA Sahasarabhojane Pranoti P Kalia Awdhesh A Shelburne Samuel A SA

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20180701 3

<h4>Background</h4>Pathobionts, bacteria that are typically human commensals but can cause disease, contribute significantly to antimicrobial resistance. Staphylococcus epidermidis is a prototypical pathobiont as it is a ubiquitous human commensal but also a leading cause of healthcare-associated bacteremia. We sought to determine the etiology of a recent increase in invasive S. epidermidis isolates resistant to linezolid.<h4>Methods</h4>Whole-genome sequencing (WGS) was performed on 176 S. epid ...[more]

PMID: 29546356

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Project description:S. epidermidis is a substantial component of the human skin microbiota, but also one of the major causes of nosocomial infection in the context of implanted medical devices. We here aimed to advance the understanding of S. epidermidis genotypes and phenotypes conducive to infection establishment. Furthermore, we investigate the adaptation of individual clonal lines to the infection lifestyle based on the detailed analysis of individual S. epidermidis populations of 23 patients suffering from prosthetic joint infection. Analysis of invasive and colonizing S. epidermidis provided evidence that invasive S. epidermidis are characterized by infection-supporting phenotypes (e.g. increased biofilm formation, growth in nutrient poor media and antibiotic resistance), as well as specific genetic traits. The discriminating gene loci were almost exclusively assigned to the mobilome. Here, in addition to IS256 and SCCmec, chromosomally integrated phages was identified for the first time. These phenotypic and genotypic features were more likely present in isolates belonging to sequence type (ST) 2. By comparing seven patient-matched nasal and invasive S. epidermidis isolates belonging to identical genetic lineages, infection-associated phenotypic and genotypic changes were documented. Besides increased biofilm production, the invasive isolates were characterized by better growth in nutrient-poor media and reduced hemolysis. By examining several colonies grown in parallel from each infection, evidence for genetic within-host population heterogeneity was obtained. Importantly, subpopulations carrying IS insertions in agrC, mutations in the acetate kinase (AckA) and deletions in the SCCmec element emerged in several infections. In summary, these results shed light on the multifactorial processes of infection adaptation and demonstrate how S. epidermidis is able to flexibly repurpose and edit factors important for colonization to facilitate survival in hostile infection environments.

Project description:Multidrug resistance among various bacterial strains is leading to worldwide resistance to a wide range of antibiotics. Combination therapy involving current antibiotics and other biological or chemical molecules represents an attractive novel strategy. In this study, we investigated the synergistic antibacterial activity of a series of Trp-containing antimicrobial peptides (AMPs) with four classes of traditional chemical antibiotics that are inactive against multidrug-resistant Staphylococcus epidermidis (MRSE) in vitro and in vivo. Among the antibiotics that we studied, penicillin, ampicillin and erythromycin showed a distinct synergistic effect in combination with all of the Trp-containing AMPs, represented by a fractional inhibitory concentration index (FICI) of <0.5. The antibacterial activities were noticeably improved, with 32-to 64-fold reductions in the MIC values for ampicillin and 16- to 32-fold reductions in the MIC values for erythromycin and penicillin. Tetracycline showed synergistic activity with only I1WL5W but additive activity with L11W, L12W, and I4WL5W. Ceftazidime exhibited additive activity with the Trp-containing peptides. In addition, the antibiotics in combination with the peptide significantly inhibited biofilm formation by MRSE 1208. A mechanistic study demonstrated that the Trp-containing peptides, especially I1WL5W and I4WL5W, which contain two tryptophan residues, disrupted bacterial inner and outer membranes, which promoted antibiotic delivery into the cytoplasm and access to cytoplasmic targets; however, L11W and L12W may have increased intracellular antibiotic concentrations by decreasing blaZ, tet(m) and msrA expression. Importantly, strong synergistic activity against the MRSE 1208 strain was observed for the combination of I1WL5W and penicillin in a mouse infection model. Thus, the combination of AMPs and traditional antibiotics could be a promising option for the prevention of acute and chronic infections caused by MRSE.

Project description:Background: Staphylococcus epidermidis is a common skin commensal that has emerged as a pathogen in hospitals, mainly related to medical devices-associated infections. Noteworthy, infection rates by S. epidermidis have the tendency to rise steeply in next decades together with medical devices use and immunocompromized population growth. Staphylococcus epidermidis population structure includes two major clonal lineages (A/C and B) that present contrasting pathogenic potentials. To address this distinction and explore the basis of increased pathogenicity of A/C lineage, we performed a detailed comparative analysis using phylogenetic and integrated pangenome-wide-association study (panGWAS) approaches and compared the lineages's phenotypes in in vitro conditions mimicking carriage and infection. Results: Each S. epidermidis lineage had distinct phenotypic signatures in skin and infection conditions and differed in genomic content. Combination of phenotypic and genotypic data revealed that both lineages were well adapted to skin environmental cues. However, they appear to occupy different skin niches, perform distinct biological functions in the skin and use different mechanisms to complete the same function: lineage B strains showed evidence of specialization to survival in microaerobic and lipid rich environment, characteristic of hair follicle and sebaceous glands; lineage A/C strains showed evidence for adaption to diverse osmotic and pH conditions, potentially allowing them to occupy a broader and more superficial skin niche. In infection conditions, A/C strains had an advantage, having the potential to bind blood-associated host matrix proteins, form biofilms at blood pH, resist antibiotics and macrophage acidity and to produce proteases. These features were observed to be rare in the lineage B strains. PanGWAS analysis produced a catalog of putative S. epidermidis virulence factors and identified an epidemiological molecular marker for the more pathogenic lineage. Conclusion: The prevalence of A/C lineage in infection is probably related to a higher metabolic and genomic versatility that allows rapid adaptation during transition from a commensal to a pathogenic lifestyle. The putative virulence and phenotypic factors associated to A/C lineage constitute a reliable framework for future studies on S. epidermidis pathogenesis and the finding of an epidemiological marker for the more pathogenic lineage is an asset for the management of S. epidermidis infections.

Dataset Information

Clonal Emergence of Invasive Multidrug-Resistant Staphylococcus epidermidis Deconvoluted via a Combination of Whole-Genome Sequencing and Microbiome Analyses.

Publications

Clonal Emergence of Invasive Multidrug-Resistant Staphylococcus epidermidis Deconvoluted via a Combination of Whole-Genome Sequencing and Microbiome Analyses.

Similar Datasets

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