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Do Staphylococcus epidermidis Genetic Clusters Predict Isolation Sources?

ABSTRACT: Staphylococcus epidermidis is a ubiquitous colonizer of human skin and a common cause of medical device-associated infections. The extent to which the population genetic structure of S. epidermidis distinguishes commensal from pathogenic isolates is unclear. Previously, Bayesian clustering of 437 multilocus sequence types (STs) in the international database revealed a population structure of six genetic clusters (GCs) that may reflect the species' ecology. Here, we first verified the presence of six GCs, including two (GC3 and GC5) with significant admixture, in an updated database of 578 STs. Next, a single nucleotide polymorphism (SNP) assay was developed that accurately assigned 545 (94%) of 578 STs to GCs. Finally, the hypothesis that GCs could distinguish isolation sources was tested by SNP typing and GC assignment of 154 isolates from hospital patients with bacteremia and those with blood culture contaminants and from nonhospital carriage. GC5 was isolated almost exclusively from hospital sources. GC1 and GC6 were isolated from all sources but were overrepresented in isolates from nonhospital and infection sources, respectively. GC2, GC3, and GC4 were relatively rare in this collection. No association was detected between fdh-positive isolates (GC2 and GC4) and nonhospital sources. Using a machine learning algorithm, GCs predicted hospital and nonhospital sources with 80% accuracy and predicted infection and contaminant sources with 45% accuracy, which was comparable to the results seen with a combination of five genetic markers (icaA, IS256, sesD [bhp], mecA, and arginine catabolic mobile element [ACME]). Thus, analysis of population structure with subgenomic data shows the distinction of hospital and nonhospital sources and the near-inseparability of sources within a hospital.

SUBMITTER: Tolo I

PROVIDER: S-EPMC4922092 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Staphylococcus epidermidis has become an important nosocomial pathogen. Multidrug resistance makes S. epidermidis infections difficult to treat. The study aims to describe the genomic characteristics of methicillin-resistant S. epidermidis (MRSE) isolated from clinical sources, to comprehend the genetic basis of antibiotic resistance, virulence, and potential pathogenicity. Sixteen MRSE underwent whole-genome sequencing, and bioinformatics analyses were carried out to ascertain their resistome, virulome, mobilome, clonality, and phylogenomic relationships. In all, 75% of isolates displayed multidrug resistance and were associated with the carriage of multiple resistance genes including mecA, blaZ, tet(K), erm(A), erm(B), erm(C), dfrG, aac(6')-aph(2''), and cat(pC221) conferring resistance to β-lactams, tetracyclines, macrolide-lincosamide-streptogramin B, aminoglycosides, and phenicols, which were located on both plasmids and chromosomes. Their virulence profiles were evidenced by the presence of genes involved in adherence/biofilm formation (icaA, icaB, icaC, atl, ebh, and ebp), immune evasion (adsA, capC, and manA), and antiphagocytosis (rmlC, cdsA, and A). The community-acquired SCCmec type IV was the most common SCCmec type. The CoNS belonged to seven multilocus sequence types (MLSTs) and carried a diversity of mobile genetic elements such as phages, insertion sequences, and plasmids. The bacterial anti-phage defense systems clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR-Cas) immunity phage system and restriction-modification system (R-M system) and the arginine catabolic mobile element (ACME) involved in immune evasion and transport of virulence genes were also found. The insertion sequence, IS256, linked with virulence, was found in 56.3% of isolates. Generally, the isolates clustered according to STs, with some similarity but also considerable variability within isolates. Whole-genome sequencing and bioinformatics analysis provide insights into the likely pathogenicity and antibiotic resistance of S. epidermidis, necessitating surveillance of this emerging pathogen.

Project description:Staphylococcus epidermidis is a ubiquitous human commensal skin bacterium that is also one of the most prevalent nosocomial pathogens. The genetic factors underlying this remarkable lifestyle plasticity are incompletely understood, mainly due to the difficulties of genetic manipulation, precluding high-throughput functional profiling of this species. To probe the versatility of S. epidermidis to survive across a diversity of environmental conditions, we developed a large-scale CRISPR interference (CRISPRi) screen complemented by transcriptional profiling (RNA sequencing) across 24 diverse conditions and piloted a droplet-based CRISPRi approach to enhance throughput and sensitivity. We identified putative essential genes, importantly revealing amino acid metabolism as crucial to survival across diverse environments, and demonstrated the importance of trace metal uptake for survival under multiple stress conditions. We identified pathways significantly enriched and repressed across our range of stress and nutrient-limited conditions, demonstrating the considerable plasticity of S. epidermidis in responding to environmental stressors. Additionally, we postulate a mechanism by which nitrogen metabolism is linked to lifestyle versatility in response to hyperosmotic challenges, such as those encountered on human skin. Finally, we examined the survival of S. epidermidis under acid stress and hypothesize a role for cell wall modification as a vital component of the survival response under acidic conditions. Taken together, this study integrates large-scale CRISPRi and transcriptomics data across multiple environments to provide insights into a keystone member of the human skin microbiome. Our results additionally provide a valuable benchmarking analysis for CRISPRi screens and are a rich resource for other staphylococcal researchers. IMPORTANCE Staphylococcus epidermidis is a bacteria that broadly inhabits healthy human skin, yet it is also a common cause of skin infections and bloodstream infections associated with implanted medical devices. Because human skin has many different types of S. epidermidis, each containing different genes, our goal is to determine how these different genes allow S. epidermidis to switch from healthy growth in the skin to being an infectious pathogen. Understanding this switch is critical to developing new strategies to prevent and treat S. epidermidis infections.

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Do Staphylococcus epidermidis Genetic Clusters Predict Isolation Sources?

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