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Staphylococcus aureus ST398 gene expression profiling during ex vivo colonization of porcine nasal epithelium

ABSTRACT: Staphylococcus aureus is a common human and animal opportunistic pathogen. In humans nasal carriage of S. aureus is a risk factor for various infections. Methicillin-resistant S. aureus ST398 is highly prevalent in pigs in Europe and North America. The mechanism of successful pig colonization by MRSA ST398 is poorly understood. Previously, we developed a nasal colonization model of porcine nasal mucosa explants to identify molecular traits involved in nasal MRSA colonization of pigs. Here, we report the analysis of the transcriptome of MRSA ST398 strain S0462 during colonization on the explant epithelium. Major regulated genes were encoding metabolic processes and regulation of these genes represents metabolic adaptation to nasal mucosa explants. Colonization was not accompanied by significant changes in transcripts of main virulence associated genes or known human colonization factors. Here, we document regulation of two genes which have potential influence on S. aureus colonization; cysteine extracellular proteinase (scpA) and von Willebrand factor-binding protein (vwbp, located on SaPIbov5). Colonization with isogenic-deletion strains (Δvwbp and ΔscpA) did not alter the nasal S. aureus colonization compared to wild type. Our results suggest that nasal colonization with MRSA ST398 is a complex event that is accompanied with changes in bacterial gene expression regulation and metabolic adaptation.

ORGANISM(S): Staphylococcus aureus

PROVIDER: GSE47910 | GEO | 2015/12/31

SECONDARY ACCESSION(S): PRJNA208301

REPOSITORIES: GEO

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Staphylococcus aureus ST398 gene expression profiling during ex vivo colonization of porcine nasal epithelium

Project description:Staphylococcus aureus is a common human and animal opportunistic pathogen. In humans nasal carriage of S. aureus is a risk factor for various infections. Methicillin-resistant S. aureus ST398 is highly prevalent in pigs in Europe and North America. The mechanism of successful pig colonization by MRSA ST398 is poorly understood. Previously, we developed a nasal colonization model of porcine nasal mucosa explants to identify molecular traits involved in nasal MRSA colonization of pigs. Here, we report the analysis of the transcriptome of MRSA ST398 strain S0462 during colonization on the explant epithelium. Major regulated genes were encoding metabolic processes and regulation of these genes represents metabolic adaptation to nasal mucosa explants. Colonization was not accompanied by significant changes in transcripts of main virulence associated genes or known human colonization factors. Here, we document regulation of two genes which have potential influence on S. aureus colonization; cysteine extracellular proteinase (scpA) and von Willebrand factor-binding protein (vwbp, located on SaPIbov5). Colonization with isogenic-deletion strains (Î?vwbp and Î?scpA) did not alter the nasal S. aureus colonization compared to wild type. Our results suggest that nasal colonization with MRSA ST398 is a complex event that is accompanied with changes in bacterial gene expression regulation and metabolic adaptation. Number of the samples: 5 (timepoint 0 min, 30 min, 60 min, 90 min and 180 min) in 4 replicates. 4 control samples

2015-12-31 | E-GEOD-47910 | biostudies-arrayexpress

Comparative genomics of Staphylococcus aureus and the application of a “pan-genome” for assigning RNA-Seq transcript reads from divergent strains and in vivo human nasal samples

Project description:in vitro comparison between two MRSA grown in rich (BHI) and poor media (SNM), compared with the nasal metatranscriptome reads of S. aureus. Global expression profile of two MRSA strains of S.aureus harvested in two different growth phases and compared with a metatranscriptome nose sample of a S. aureus carrier.

2015-01-05 | E-GEOD-56294 | biostudies-arrayexpress

Comparative genomics of Staphylococcus aureus and the application of a “pan-genome” for assigning RNA-Seq transcript reads from divergent strains and in vivo human nasal samples

Project description:in vitro comparison between two MRSA grown in rich (BHI) and poor media (SNM), compared with the nasal metatranscriptome reads of S. aureus.

2015-01-05 | GSE56294 | GEO

The differential gene expressions of rat mucosa colonized with single or multi-species of MRSA or PA were studied using RNA-sequencing of total transcriptome.

Project description:The differential gene expressions of rat mucosa colonized with single or multi-species of MRSA or PA were studied using RNA-sequencing of total transcriptome. In multi-species in-vitro biofilms PA partially inhibited SA growth. However, no significant inhibition of MRSA was detected during in-vivo colonization of multi-species in rat bullae. A total of 1797 genes were significantly (p < 0.05) differentially expressed in MRSA or PA or MRSA+PA colonized rat middle ear mucosa with respect to the control. The poly-microbial colonization of MRSA and PA induced the differential expression of a significant number of genes that are involved in immune response, inflammation, signaling, development, and defense; these were not expressed with single species colonization by either MRSA or PA. Genes involved in defense, immune response, inflammatory response, and developmental process were exclusively up-regulated, and genes that are involved in nervous system signaling, development and transmission, regulation of cell growth and development, anatomical and system development, and cell differentiation were down-regulated after multi-species inoculation.

2018-01-15 | GSE94722 | GEO

Characterization of Peripheral Blood Mononuclear Cells Gene Expression Profiles of Pediatric Staphylococcus aureus Persistent and Non-Carriers

Project description:Defects in innate immunity affect many different physiologic systems and several studies of patients with primary immunodeficiency disorders demonstrated the importance of innate immune system components in disease prevention or colonization of bacterial pathogens. To assess the role of the innate immune system on nasal colonization with Staphylococcus aureus, innate immune responses in pediatric S. aureus nasal persistent carriers (n=3) and non-carriers (n=3) were profiled by RNAseq. We stimulated previously frozen peripheral blood mononuclear cells (PBMCs) from these subjects with i) live S. aureus (a mixture of all carriage isolates), or ii) heat-killed S. aureus.PBMC gene expression profiles differed between persistent and non-S. aureus carriers following stimulation with either live or dead S. aureus. These observations suggest that individuals susceptible to persistent carriage with S. aureus may possess differences in their live/dead bacteria recognition pathway and that innate pathway signaling is different between persistent and non-carriers of S. aureus.

2020-12-07 | GSE153122 | GEO

Transcription profiling of S. aureus to investigate an outbreak of severe infections with community-acquired methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin following immunization - duplicate of E-BUGS-45

Project description:BACKGROUND: Infections with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are emerging worldwide. We investigated an outbreak of severe CA-MRSA infections in children following out-patient vaccination. METHODS AND FINDINGS: We carried out a field investigation after adverse events following immunization (AEFI) were reported. We reviewed the clinical data from all cases. S. aureus recovered from skin infections and from nasal and throat swabs were analyzed by pulse-field gel electrophoresis, multi locus sequence typing, PCR and microarray. In May 2006, nine children presented with AEFI, ranging from fatal toxic shock syndrome, necrotizing soft tissue infection, purulent abscesses, to fever with rash. All had received a vaccination injection in different health centres in one District of Ho Chi Minh City. Eight children had been vaccinated by the same health care worker (HCW). Deficiencies in vaccine quality, storage practices, or preparation and delivery were not found. Infection control practices were insufficient. CA-MRSA was cultured in four children and from nasal and throat swabs from the HCW. Strains from children and HCW were indistinguishable. All carried the Panton-Valentine leukocidine (PVL), the staphylococcal enterotoxin B gene, the gene complex for staphylococcal-cassette-chromosome mec type V, and were sequence type 59. Strain HCM3A is epidemiologically unrelated to a strain of ST59 prevalent in the USA, although they belong to the same lineage. CONCLUSIONS: We describe an outbreak of infections with CA-MRSA in children, transmitted by an asymptomatic colonized HCW during immunization injection. Consistent adherence to injection practice guidelines is needed to prevent CA-MRSA transmission in both in- and outpatient settings. Data is also available from http://bugs.sgul.ac.uk/E-BUGS-45

2009-01-16 | E-BUGS-45 | biostudies-arrayexpress

Gene expression in synthetic nasal medium

Project description:Staphylococcus aureus prefers the human anterior nares as its habitat, but nothing is known about the nutritional situation in this ecological niche. Analysis of nasal secretions showed a complex mixture of nutrients at low concentration. Based on these findings a synthetic nasal medium (SNM) was composed, mimicking nasal secretions. We used microarrays in order to investigate pathways and expression patterns important in a synthetic medium mimicking nasal secretions compared to standard laboratory complex medium Staphylococcus aureus USA300 was inoculated in complex medium (BM) or synthetic nasal medium (SNM) to an OD578nm of 0.005 and grown under aerobic conditions until OD578nm of 0.02. RNA was stabilized and extracted at this early growth phase and hybridization was made on Affymetrix microarrays. The aim was to identify genes which are important during growth under the limited conditions present during colonization of human nares

2013-04-10 | E-GEOD-43712 | biostudies-arrayexpress

Metabolic Adaptation of Staphylococcus aureus to Host Immunity

Project description:This project is intended to study the metabolic adaptation of Methicillin-Resistant Staphylococcus aureus (MRSA) to host immunity. Because of the nature of the samples RTI RCMRC worked with Dr. Anthony R. Richardson so that the samples would be extracted at the University of North Carolina at Chapel Hill under the condition that were optimized by RTI RCMRC for broad spectrum metabolomics analysis.

2017-09-10 | ST000453 | MetabolomicsWorkbench

Whole-genome comparison of meticillin-resistant Staphylococcus aureus CC22 SCCmecIV from people and their in-contact pets.

Project description:BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) infections remain important medical and veterinary challenges. The MRSA isolated from dogs and cats typically belong to dominant hospital-associated clones, in the UK mostly EMRSA-15 (CC22 SCCmecIV), suggesting original human-to-animal transmission. Nevertheless, little is known about host-specific genetic variation within the same S. aureus lineage. HYPOTHESIS/OBJECTIVES: To identify host-specific variation amongst MRSA CC22 SCCmecIV by comparing isolates from pets with those from in-contact humans using whole-genome microarray. METHODS: Six pairs of MRSA CC22 SCCmecIV from human carriers (owners and veterinary staff) and their respective infected in-contact pets were compared using a 62-strain whole-genome S. aureus microarray (SAM-62). The presence of putative host-specific genes was subsequently determined in a larger number of human (n = 47) and pet isolates (n = 93) by PCR screening. RESULTS: Variation in mobile genetic elements (MGEs) occurred frequently and appeared largE: The variation found amongst MGEs highlights that genetic adaptation in MRSA continues. However, host-specific MGEs were not detected, which supports the hypothesis that pets may not be natural hosts of MRSA CC22 and emphasizes that rigorous hygiene measures are critical to prevent contamination and infection of dogs and cats. The host specificity of individual heavy-metal resistance genes warrants further investigation into different selection pressures in humans and animals.

2013-11-02 | E-BUGS-138 | biostudies-arrayexpress

Role of the accessory gene regulator agr in community-associated MRSA pathogenesis

Project description:The success of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) as pathogens is due to a combination of antibiotic resistance with high virulence. However, evolution of the exceptional virulence potential of CA-MRSA is not understood. Our previous study indicated that differential gene expression contributes substantially to this process. Thus, we here investigated the role of the pivotal virulence gene regulatory system agr in the most prevalent CA-MRSA strain USA300. Using a mouse subcutaneous infection model, we show that agr is essential for the development of CA-MRSA skin infections, the most frequent manifestation of disease caused by CA-MRSA. Furthermore, genome-wide analysis of gene expression revealed significant differences in agr-dependent virulence gene regulation between CA-MRSA, HA-MRSA, and laboratory strains. Our findings demonstrate that agr functionality is critical for CA-MRSA disease and indicate that an adaptation of the agr regulon to optimize expression of a broad set of virulence determinants may have contributed to the evolution of exceptionally pronounced virulence of CA-MRSA strains. Keywords: wild type vs mutant Wild type vs mutant agr strains.

2011-03-29 | E-GEOD-18793 | biostudies-arrayexpress

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