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JCI Insight May 2018The underlying pathology of atopic dermatitis (AD) includes impaired skin barrier function, susceptibility to Staphylococcus aureus skin infection, immune dysregulation,...
The underlying pathology of atopic dermatitis (AD) includes impaired skin barrier function, susceptibility to Staphylococcus aureus skin infection, immune dysregulation, and cutaneous dysbiosis. Our recent investigation into the potential role of Gram-negative skin bacteria in AD revealed that isolates of one particular commensal, Roseomonas mucosa, collected from healthy volunteers (HVs) improved outcomes in mouse and cell culture models of AD. In contrast, isolates of R. mucosa from patients with AD worsened outcomes in these models. These preclinical results suggested that interventions targeting the microbiome could provide therapeutic benefit for patients with AD. As a first test of this hypothesis in humans, 10 adult and 5 pediatric patients were enrolled in an open-label phase I/II safety and activity trial (the Beginning Assessment of Cutaneous Treatment Efficacy for Roseomonas in Atopic Dermatitis trial; BACTERiAD I/II). Treatment with R. mucosa was associated with significant decreases in measures of disease severity, topical steroid requirement, and S. aureus burden. There were no adverse events or treatment complications. We additionally evaluated differentiating bacterial metabolites and topical exposures that may contribute to the skin dysbiosis associated with AD and/or influence future microbiome-based treatments. These early results support continued evaluation of R. mucosa therapy with a placebo-controlled trial.
Topics: Adolescent; Adult; Animals; Biological Therapy; Child; Dermatitis, Atopic; Dysbiosis; Female; Humans; Male; Methylobacteriaceae; Mice; Microbiota; Severity of Illness Index; Skin; Staphylococcus aureus; Steroids; Young Adult
PubMed: 29720571
DOI: 10.1172/jci.insight.120608 -
Frontiers in Immunology 2022The cutaneous microbiome is increasingly recognized as a contributor to skin diseases like atopic dermatitis (AD) and psoriasis. Although traditionally AD and psoriasis...
The cutaneous microbiome is increasingly recognized as a contributor to skin diseases like atopic dermatitis (AD) and psoriasis. Although traditionally AD and psoriasis have been viewed as having opposing immunologic findings, recent evidence suggests an overlap in ceramide-family lipid production in the protection against symptoms. We recently identified that specific environmental pollutants may drive dysbiosis through direct suppression of ceramide-family lipids produced by health-associated skin bacteria in atopic dermatitis (AD). We further demonstrated that one such bacteria, , generated significant clinical improvement in AD lasting beyond active treatment lipid-mediated modulation of tumor necrosis factor (TNF) signaling. To assess the potential preclinical benefit of in psoriasis we assessed for direct effects on surface TNF signaling in cell cultures and identified direct effects on the TNF axis. We also identified preclinical efficacy of treatment in the imiquimod mouse model of psoriasis. Finally, we expanded our previous environmental assessment for psoriasis to include more traditional markers of air quality and found a strong association between disease rates and ambient carbon monoxide (CO), nitrogen dioxide (NO), and particulate matter (PM). At the current stage this work is speculative but does support consideration of further preclinical models and/or clinical assessments to evaluate any potential for therapeutic benefit through microbial manipulation and/or environmental mitigation.
Topics: Animals; Mice; Dermatitis, Atopic; Environmental Pollutants; Psoriasis; Ceramides; Lipids
PubMed: 36605199
DOI: 10.3389/fimmu.2022.1094376 -
Frontiers in Cellular and Infection... 2018As therapies for atopic dermatitis (AD) based on live biotherapeutic products (LBP) are developed, the potential displacement of biotherapeutic strains, and species to...
As therapies for atopic dermatitis (AD) based on live biotherapeutic products (LBP) are developed, the potential displacement of biotherapeutic strains, and species to mucosal sites where they are not naturally found is of investigative interest. However, formal assessment of the toxicity potential of healthy skin commensal organisms has not been reported in the literature. Our previous research indicates that topical application of live to treat AD was associated with clinical benefit on the skin, but the effects of exposure via inhalation, eye inoculation, and ingestion were unknown. Herein we report our findings from mice inoculated with commensal strains of , coagulase negative (CNS), and . Bacterial isolates were collected under clinical trial NCT03018275, however these results do not represent an interventional clinical trial. Our tested R. mucosa isolates did not display significant infection or inflammation. However, neutropenic mice inoculated with CNS had infection without major inflammation in pulmonary models. In contrast, systemic infection generated hepatic and splenic pathology for and CNS, which was worsened by the presence of neutropenia. Our results suggest that LBP derived from bacteria without significant infectivity histories, such as , may represent safer options than known pathobionts like and spp. Overall, these results suggest that topically applied LBP from select skin commensals are likely to present safe therapeutic options and reinforce our prior clinical findings.
Topics: Animals; Bacterial Infections; Carrier State; Disease Models, Animal; Methylobacteriaceae; Mice; Probiotics; Pseudomonas aeruginosa; Staphylococcus; Symbiosis; Virulence
PubMed: 30719426
DOI: 10.3389/fcimb.2018.00451 -
Infection & Chemotherapy Sep 2015Roseomonas are a gram-negative bacteria species that have been isolated from environmental sources. Human Roseomonas infections typically occur in immunocompromised...
Roseomonas are a gram-negative bacteria species that have been isolated from environmental sources. Human Roseomonas infections typically occur in immunocompromised patients, most commonly as catheter-related bloodstream infections. However, Roseomonas infections are rarely reported in immunocompetent hosts. We report what we believe to be the first case in Korea of infectious spondylitis with bacteremia due to Roseomonas mucosa in an immunocompetent patient who had undergone vertebroplasty for compression fractures of his thoracic and lumbar spine.
PubMed: 26483995
DOI: 10.3947/ic.2015.47.3.194 -
Cureus Jun 2023species has been associated with infections in both immunocompetent and immunocompromised hosts, manifesting as peritonitis, bacteremia, catheter-related bacteremia,...
species has been associated with infections in both immunocompetent and immunocompromised hosts, manifesting as peritonitis, bacteremia, catheter-related bacteremia, endophthalmitis, spondylitis, and endocarditis. Here we present a man in his 60s who was brought to our institution for sudden onset of aphasia, right-sided paresthesia, and new onset tonic-clonic seizure episodes. At presentation, he was found to have severe lactic acidosis, acute kidney failure, bilateral hydronephrosis, elevated prostate-specific antigen (PSA), and an enlarged prostate. Blood cultures obtained on admission later grew species for which he was started on meropenem. A trans-esophageal echocardiogram (TEE) showed multiple very thin mobile densities on the ventricular side of the aortic valve; magnetic resonance imaging (MRI) of the brain revealed an 11 mm acute/subacute hemorrhage. The patient was discharged in stable condition on Ertapenem intravenous therapy for six weeks. can be a cause of endocarditis. The antimicrobial resistance profile of suggests that carbapenems, fluoroquinolones or aminoglycosides are the drugs of choice for Roseomonas infections and that infectious diseases involved in cases of infections should be instituted promptly for proper management.
PubMed: 37448416
DOI: 10.7759/cureus.40318 -
Clinical Microbiology and Infection :... Aug 2016Roseomonas spp. are increasingly involved in human infectious diseases. The environmental source for infection is generally admitted in published cases owing to the...
Roseomonas spp. are increasingly involved in human infectious diseases. The environmental source for infection is generally admitted in published cases owing to the origin of most Roseomonas species and to their affiliation to the family Acetobacteraceae in Rhodospirillales, which mainly groups environmental bacteria. For a better delineation of Roseomonas habitat and infectious reservoir, we related phenotype, phylotype (16S rRNA gene), genomotype (pulsed-field gel electrophoresis) and origin of 33 strains isolated from humans, hospital environment and natural environment. Genetic and metagenomic databases were also surveyed. The population structure of the genus showed clades associated with humans, whereas others grouped environmental strains only. Roseomonas mucosa is the main human-associated species and the study supported the idea that opportunistic infections due to this species are related to the patient skin microbiota rather than to the environment. In contrast, some strains belonging to other species isolated from patients with cystic fibrosis were related to environmental clades, suggesting an exogenous source for patient colonization. Accurate knowledge about the reservoirs of opportunistic pathogens that have long been considered of environmental origin is still needed and would be helpful to improve infection control and epidemiological survey of emerging human pathogens.
Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Environmental Microbiology; Genome, Bacterial; Gram-Negative Bacterial Infections; Humans; Metagenome; Metagenomics; Methylobacteriaceae; Microbial Sensitivity Tests; Microbiota; Opportunistic Infections; Phylogeny; RNA, Ribosomal, 16S; Skin
PubMed: 27269884
DOI: 10.1016/j.cmi.2016.05.024 -
Annals of Laboratory Medicine Jul 2016Roseomonas is a genus of pink-pigmented nonfermentative bacilli. These slow-growing, gram-negative cocobacilli form pink-colored colonies on sheep blood agar. They...
Roseomonas is a genus of pink-pigmented nonfermentative bacilli. These slow-growing, gram-negative cocobacilli form pink-colored colonies on sheep blood agar. They differ from other pink-pigmented nonfermenters, including Methylobacterium, in morphology, biochemical characteristics, and DNA sequence. Roseomonas strains are rarely isolated in clinical laboratories; therefore, we report two cases in order to improve our ability to identify these pathogens. We isolated two strains of Roseomonas mucosa from the venous blood cultures of two patients, an 84-yr-old woman with common bile duct obstruction and a 17-yr-old male with acute myeloid leukemia who had an indwelling central-venous catheter for chemotherapy. The isolated strains were confirmed as R. mucosa by 16S rRNA sequencing.
PubMed: 27139611
DOI: 10.3343/alm.2016.36.4.367 -
A Case of Successfully Treated Roseomonas mucosa-induced Peritonitis Diagnosed by Mass Spectrometry.Internal Medicine (Tokyo, Japan) Jan 2024Roseomonas mucosa is difficult to identify using routine analytical techniques. We herein report a case of peritoneal dialysis (PD)-related peritonitis caused by R....
Roseomonas mucosa is difficult to identify using routine analytical techniques. We herein report a case of peritoneal dialysis (PD)-related peritonitis caused by R. mucosa identified using matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry (MS). A 70-year-old woman was admitted to our hospital with PD-related peritonitis. Blood agar medium of dialysate culture derived colony pale pink in color, and the organism was identified as R. mucosa using MALDI-TOF MS. She was successfully treated with ciprofloxacin and meropenem without catheter removal. To our knowledge, this is the first case of R. mucosa peritonitis in which technique failure has been avoided.
PubMed: 38220190
DOI: 10.2169/internalmedicine.2998-23 -
American Journal of Clinical Dermatology Feb 2020The efficacy of antibiotics in rosacea treatment suggests a role for microorganisms in its pathophysiology. Growing concern over the adverse effects of antibiotic use...
BACKGROUND
The efficacy of antibiotics in rosacea treatment suggests a role for microorganisms in its pathophysiology. Growing concern over the adverse effects of antibiotic use presents a need for targeted antimicrobial treatment in rosacea.
OBJECTIVE
We performed a case-control study to investigate the skin microbiota in patients with rosacea compared to controls matched by age, sex, and race.
METHODS
Nineteen participants with rosacea, erythematotelangiectatic, papulopustular, or both, were matched to 19 rosacea-free controls. DNA was extracted from skin swabs of the nose and bilateral cheeks of participants. Sequencing of the V3V4 region of the bacterial 16S ribosomal RNA gene was performed using Illumina MiSeq and analyzed using QIIME/MetaStats 2.0 software.
RESULTS
Compared with controls, skin microbiota in erythematotelangiectatic rosacea was depleted in Roseomonas mucosa (p = 0.004). Papulopustular rosacea was enriched in Campylobacter ureolyticus (p = 0.001), Corynebacterium kroppenstedtii (p = 0.008), and the oral flora Prevotella intermedia (p = 0.001). The highest relative abundance of C. kroppenstedtii was observed in patients with both erythematotelangiectatic and papulopustular rosacea (19.2%), followed by papulopustular (5.06%) and erythematotelangiectatic (1.21%) rosacea. C. kroppenstedtii was also associated with more extensive disease, with the highest relative abundance in rosacea affecting both the cheeks and nose (2.82%), followed by rosacea sparing the nose (1.93%), and controls (0.19%).
CONCLUSIONS
The skin microbiota in individuals with rosacea displays changes from that of healthy skin, suggesting that further studies examining a potential role for the skin microbiota in the pathophysiology of rosacea may be warranted.
Topics: Adult; Aged; Bacteria; Case-Control Studies; Female; Humans; Male; Microbiota; Middle Aged; Rosacea; Skin; Young Adult
PubMed: 31502207
DOI: 10.1007/s40257-019-00471-5 -
PloS One 2023We recently used EPA databases to identify that isocyanates, most notably toluene diisocyanate (TDI), were the pollutant class with the strongest spatiotemporal and...
We recently used EPA databases to identify that isocyanates, most notably toluene diisocyanate (TDI), were the pollutant class with the strongest spatiotemporal and epidemiologic association with atopic dermatitis (AD). Our findings demonstrated that isocyanates like TDI disrupted lipid homeostasis and modeled benefit in commensal bacteria like Roseomonas mucosa through disrupting nitrogen fixation. However, TDI has also been established to activate transient receptor potential ankyrin 1 (TRPA1) in mice and thus could directly contribute to AD through induction of itch, rash, and psychological stress. Using cell culture and mouse models, we now demonstrate that TDI induced skin inflammation in mice as well as calcium influx in human neurons; each of these findings were dependent on TRPA1. Furthermore, TRPA1 blockade synergized with R. mucosa treatment in mice to improve TDI-independent models of AD. Finally, we show that the cellular effects of TRPA1 are related to shifting the balance of the tyrosine metabolites epinephrine and dopamine. This work provides added insight into the potential role, and therapeutic potential, or TRPA1 in the pathogenesis of AD.
Topics: Humans; Animals; Mice; Dermatitis, Atopic; Exanthema; Pruritus; Isocyanates; Toluene 2,4-Diisocyanate; Cytoskeletal Proteins; TRPA1 Cation Channel
PubMed: 36877675
DOI: 10.1371/journal.pone.0282569