المؤلفون: Sans de San Nicolàs, Lídia

المساهمون: University/Department: Universitat de Barcelona. Departament de Biologia Cel·lular, Fisiologia i Immunologia

مرشدي الرسالة: Santamaria Babí, Luis F.

المصدر: TDX (Tesis Doctorals en Xarxa)

مصطلحات موضوعية: Inflamació, Inflamación, Inflammation, Dermatitis atòpica, Dermatitis atópica, Atopic dermatitis, Àcars, Ácaros, Mites, Cèl·lules T, Células T, T cells, Staphylococcus aureus, Ciències Experimentals i Matemàtiques

الوقت: 616.5

الوصف: Programa de Doctorat en Biomedicina

الوصف (مترجم): [eng] Atopic dermatitis is the most common chronic immune-mediated inflammatory skin disease affecting up to 20% of children and 10% of adults. The complex pathophysiology of the disease comprises genetic susceptibility, epidermal barrier dysfunction, cutaneous dysbiosis with abundance of S. aureus, an abnormal cutaneous immune system activation with a core Th2 response and pruritus. Cutaneous Lymphocyte-associated Antigen (CLA)+ T cells represent the subset of memory T cells that belong to the cutaneous immune system. CLA+ T cells recirculate between blood and skin through the thoracic duct, specifically respond to skin-related antigens, and represent over 90% of T cells infiltrating the skin. Therefore, CLA+ T cells constitute peripheral cellular biomarkers and, because they can be found in general circulation, they are a source of translational information on the immunological mechanisms taking place in the skin during disease. We have studied atopic dermatitis in the context of the cutaneous immune response through the effector function of CLA+ T cells. For this, we have stablished a novel ex vivo model of adult non- treated moderate-to-severe atopic dermatitis based on circulating CLA+ T cells cocultured with a suspension of autologous epidermal cells obtained from lesional biopsies in the same patients. Then, we have studied the T-cell effector function in response to relevant disease triggers such as S. aureus microorganism and house dust mite (HDM) allergen, as well as the association between cytokine response to the stimuli and patient’s clinical data. First, the study of IL-13 response to S. aureus enterotoxin B (SEB) by CLA+ T cells defined two groups of patients, Th2 high and Th2 low, within a clinically homogeneous population. In the Th2 high group, in contrast to the Th2 low group, the IL-13 response positively correlated with severity, in terms of EASI score, and levels of CCL17, sIL-2R and S. aureus-specific IgE in plasma. Additionally, in this group the IL-13 response directly correlated with CCL26 and indirectly correlated with LCN2 mRNA expression in cutaneous lesions. Conversely, in the Th2 low group, the CLA+ T-cell response to SEB skewed towards Th17, Th22 and Th1. Next, the role of the neuroimmune cytokine IL-31 was examined in our model by studying the CLA+ T-cell response to HDM, and a bimodal (present or absent) IL-31 response in relation with the HDM-specific IgE levels in plasma was observed. Patients producing IL-31 by HDM-activated CLA+ T cells showed increased HDM-specific and total IgE levels and reported an increased inflammatory profile compared to patients with no IL-31 response. Interestingly, the IL-31 response directly correlated with patient’s pruritus intensity and plasma levels of CCL27 and periostin. Of note, patients with no IL-31 response reported raised presence of HDM- specific and total IgE levels compared to control subjects, suggesting that the degree of IgE sensitization to HDM in this group was not enough for inducing IL-31 response. In summary, this novel ex vivo model of adult non-treated moderate-to-severe atopic dermatitis has allowed to functionally identify Th2 high and Th2 low responders from a clinically homogeneous population based on the SEB-CLA+-IL-13 axis, as well as stratifying patients into IL-31 producers and non-producers in relation with the degree of IgE sensitization to HDM by analyzing the CLA+ T-cell response to HDM and its association with clinical features. Altogether, this translational work expands the understanding of the heterogeneous inflammatory response of the disease and may contribute to improving the effectiveness of targeted therapies.

وصف الملف: application/pdf

الوصول الحر: http://hdl.handle.net/10803/689454Test

المؤلفون: Vázquez Sánchez, Daniel A.

المساهمون: University/Department: Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental

مرشدي الرسالة: Domínguez Luzón, Ma. Ángeles (María Ángeles), Camara Mas, Jordi

المصدر: TDX (Tesis Doctorals en Xarxa)

مصطلحات موضوعية: Epidemiologia, Epidemiología, Epidemiology, Genòmica, Genómica, Genomics, Seqüència d'aminoàcids, Cadenas de aminoácidos, Amino acid sequence, Resistència als medicaments, Resistencia a los medicamentos, Drug resistance, Staphylococcus aureus, Ciències de la Salut

الوقت: 616.9

الوصف: Programa de Doctorat en Medicina i Recerca Translacional / Tesi realitzada a l'Institut de Investigació Biomèdica de Bellvitge (IDIBELL)

الوصف (مترجم): [spa] Uno de los problemas de salud de más relevancia a nivel global es el de las infecciones por bacterias resistentes a los antibióticos. La Organización Mundial de la Salud (OMS) junto al Centro para el Control y la Prevención de Enfermedades (CDC) consideran a los patógenos resistentes a los antibióticos como una de las amenazas inminentes para la salud humana. El listado de microorganismos llamado ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter bau-mannii, Pseudomonas aeruginosa y Enterobacter spp), recoge las especies patógenas de más relevancia por su potencial de presentar resistencia a múl-tiples antibióticos. En ese sentido, S. aureus destaca por la adquisición de mecanismos de resistencia a casi todos los antibióticos empleados para su tratamiento, como los β-lactámicos, los glicopéptidos y las oxazolidinonas. MRSA a su vez, es uno de los patógenos resistentes más relevante, con una amplia distribución y asociado a infecciones hospitalarias, comunitarias e incluso ganaderas. También destaca su gran plasticidad genética, que le permite adaptarse a condiciones ambientales diversas, su capacidad patogénica y la frecuente combinación de resistencias a otros grupos de antibióticos. La accesibilidad durante la última década a técnicas de secuenciación del genoma completo de los microorganismos y la disminución de su coste económico, han cambiado la perspectiva de los estudios epidemiológicos y de la tipificación molecular. Esta tecnología ofrece la posibilidad de analizar genomas completos con un nivel de discriminación de unos pocos nucleótidos y establecer relaciones genéticas con una precisión inalcanzable por técnicas moleculares clásicas. Con una única técnica, se puede obtener una gran cantidad de información para el estudio de genes relacionados con la resistencia antibiótica, la producción de toxinas, la adherencia bacteriana y estudios de elementos móviles y fijos. Por ello, esta tesis doctoral pretende analizar la epidemiología de las infecciones por MRSA y las características clínicas de la infección bacteriémica; la dinámica poblacional de los clones de MRSA y su evolución en el tiempo y, por último, la base molecular de la resistencia a los antibióticos en MRSA, mediante la incorporación de tecnologías de secuenciación del genoma completo.

وصف الملف: application/pdf

الوصول الحر: http://hdl.handle.net/10803/688553Test

المؤلفون: Allaire, Patrick¹ (AUTHOR), Elsayed, Noha S.¹ (AUTHOR), Berg, Richard L.² (AUTHOR), Rose, Warren³ (AUTHOR), Shukla, Sanjay K.^1,4 (AUTHOR) shukla.sanjay@marshfieldresearch.org

المصدر: PLoS ONE. 7/5/2024, Vol. 19 Issue 7, p1-20. 20p.

مصطلحات موضوعية: *STAPHYLOCOCCUS aureus infections, *IRON deficiency anemia, *PHENOTYPES, *STAPHYLOCOCCUS aureus, *MICROCOCCACEAE, *MEDICAL screening, *AGE of onset

مستخلص: Background: Phenome-Wide Association study (PheWAS) is a powerful tool designed to systematically screen clinical observations derived from medical records (phenotypes) for association with a variable of interest. Despite their usefulness, no systematic screening of phenotypes associated with Staphylococcusaureusinfections (SAIs) has been done leaving potential novel risk factors or complications undiscovered. Method and cohorts: We tailored the PheWAS approach into a two-stage screening procedure to identify novel phenotypes correlating with SAIs. The first stage screened for co-occurrence of SAIs with other phenotypes within medical records. In the second stage, significant findings were examined for the correlations between their age of onset with that of SAIs. The PheWAS was implemented using the medical records of 754,401 patients from the Marshfield Clinic Health System. Any novel associations discovered were subsequently validated using datasets from TriNetX and All of Us, encompassing 109,884,571 and 118,538 patients respectively. Results: Forty-one phenotypes met the significance criteria of a p-value < 3.64e-5 and odds ratios of > 5. Out of these, we classified 23 associations either as risk factors or as complications of SAIs. Three novel associations were discovered and classified either as a risk (long-term use of aspirin) or complications (iron deficiency anemia and anemia of chronic disease). All novel associations were replicated in the TriNetX cohort. In the All of Us cohort, anemia of chronic disease was replicated according to our significance criteria. Conclusions: The PheWAS of SAIs expands our understanding of SAIs interacting phenotypes. Additionally, the novel two-stage PheWAS approach developed in this study can be applied to examine other disease-disease interactions of interest. Due to the possibility of bias inherent in observational data, the findings of this study require further investigation. [ABSTRACT FROM AUTHOR]

المؤلفون: Yu, Jingyi¹ (AUTHOR), Han, Weihua¹ (AUTHOR), Xu, Yanlei¹ (AUTHOR), Shen, Li¹ (AUTHOR), Zhao, Huilin¹ (AUTHOR), Zhang, Jiao² (AUTHOR), Xiao, Yanghua³ (AUTHOR), Guo, Yinjuan¹ (AUTHOR), Yu, Fangyou¹ (AUTHOR) wzjxyfy@163.com

المصدر: BMC Microbiology. 7/3/2024, Vol. 24 Issue 1, p1-9. 9p.

مصطلحات موضوعية: *BIOFILMS, *METHICILLIN-resistant staphylococcus aureus, *COMMENSALISM, *NOSOCOMIAL infections, *STAPHYLOCOCCUS aureus, *COMMUNITY-acquired infections, *MUCOUS membranes

مصطلحات جغرافية: JIANGXI Sheng (China), HUBEI Sheng (China), GUANGDONG Sheng (China)

مستخلص: Background: Staphylococcus aureus, a commensal bacterium, colonizes the skin and mucous membranes of approximately 30% of the human population. Apart from conventional resistance mechanisms, one of the pathogenic features of S. aureus is its ability to survive in a biofilm state on both biotic and abiotic surfaces. Due to this characteristic, S. aureus is a major cause of human infections, with Methicillin-Resistant Staphylococcus aureus (MRSA) being a significant contributor to both community-acquired and hospital-acquired infections. Results: Analyzing non-repetitive clinical isolates of MRSA collected from seven provinces and cities in China between 2014 and 2020, it was observed that 53.2% of the MRSA isolates exhibited varying degrees of ability to produce biofilm. The biofilm positivity rate was notably high in MRSA isolates from Guangdong, Jiangxi, and Hubei. The predominant MRSA strains collected in this study were of sequence types ST59, ST5, and ST239, with the biofilm-producing capability mainly distributed among moderate and weak biofilm producers within these ST types. Notably, certain sequence types, such as ST88, exhibited a high prevalence of strong biofilm-producing strains. The study found that SCCmec IV was the predominant type among biofilm-positive MRSA, followed by SCCmec II. Comparing strains with weak and strong biofilm production capabilities, the positive rates of the sdrD and sdrE were higher in strong biofilm producers. The genetic determinants ebp, icaA, icaB, icaC, icaD, icaR, and sdrE were associated with strong biofilm production in MRSA. Additionally, biofilm-negative MRSA isolates showed higher sensitivity rates to cefalotin (94.8%), daptomycin (94.5%), mupirocin (86.5%), teicoplanin (94.5%), fusidic acid (81.0%), and dalbavancin (94.5%) compared to biofilm-positive MRSA isolates. The biofilm positivity rate was consistently above 50% in all collected specimen types. Conclusions: MRSA strains with biofilm production capability warrant increased vigilance. [ABSTRACT FROM AUTHOR]

المؤلفون: Chen, Kuan‐Jen^1,2 (AUTHOR) cgr999@gmail.com, Sun, Ming‐Hui^1,2 (AUTHOR), Wu, Wei‐Chi^1,2 (AUTHOR), Lai, Chi‐Chun^1,2,3 (AUTHOR)

المصدر: Clinical & Experimental Ophthalmology. Jul2024, Vol. 52 Issue 5, p591-595. 5p.

مصطلحات موضوعية: *STAPHYLOCOCCUS aureus, *HEPATORENAL syndrome, *ENDOPHTHALMITIS, *INFECTIOUS arthritis, *URINARY tract infections, *METHICILLIN-resistant staphylococcus aureus

مستخلص: This document summarizes a study on endogenous Staphylococcus aureus endophthalmitis (ESaE), a rare but serious complication that can lead to vision loss. The study focused on cases in Taiwan and examined the source of infection, risk factors, treatments, and visual outcomes. The most common predisposing factor for ESaE was diabetes mellitus, and septic arthritis was the most frequently identified source of infection. Poor initial visual acuity and retinal detachment were predictors for worse visual outcomes. All MRSA and MSSA strains were susceptible to vancomycin. The study did not find a statistically significant difference in visual acuity outcomes between the MRSA and MSSA groups. [Extracted from the article]

المؤلفون: Xiong, Yan Q^1,2,3 (AUTHOR) yxiong@ucla.edu, Li, Yi¹ (AUTHOR), Goncheva, Mariya I⁴ (AUTHOR), Elsayed, Ahmed M¹ (AUTHOR), Zhu, Fengli¹ (AUTHOR), Li, Liang¹ (AUTHOR), Abdelhady, Wessam¹ (AUTHOR), Flannagan, Ronald S⁴ (AUTHOR), Yeaman, Michael R^1,2,3,5 (AUTHOR), Bayer, Arnold S^1,2,3 (AUTHOR), Heinrichs, David E⁴ (AUTHOR)

المصدر: Journal of Infectious Diseases. 6/15/2024, Vol. 229 Issue 6, p1648-1657. 10p.

مصطلحات موضوعية: *METHICILLIN-resistant staphylococcus aureus, *BIOSYNTHESIS, *ENDOCARDITIS, *VANCOMYCIN, *STAPHYLOCOCCUS aureus

مستخلص: Background Staphylococcus aureus is the most common cause of life-threatening endovascular infections, including infective endocarditis (IE). These infections, especially when caused by methicillin-resistant strains (MRSA), feature limited therapeutic options and high morbidity and mortality rates. Methods Herein, we investigated the role of the purine biosynthesis repressor, PurR, in virulence factor expression and vancomycin (VAN) treatment outcomes in experimental IE due to MRSA. Results The PurR-mediated repression of purine biosynthesis was confirmed by enhanced purF expression and production of an intermediate purine metabolite in purR mutant strain. In addition, enhanced expression of the transcriptional regulators, sigB and sarA , and their key downstream virulence genes (eg, fnbA , and hla) was demonstrated in the purR mutant in vitro and within infected cardiac vegetations. Furthermore, purR deficiency enhanced fnbA / fnbB transcription, translating to increased fibronectin adhesion versus the wild type and purR- complemented strains. Notably, the purR mutant was refractory to significant reduction in target tissues MRSA burden following VAN treatment in the IE model. Conclusions These findings suggest that the purine biosynthetic pathway intersects the coordination of virulence factor expression and in vivo persistence during VAN treatment, and may represent an avenue for novel antimicrobial development targeting MRSA. [ABSTRACT FROM AUTHOR]

المؤلفون: Lin Kong^1,2, Rongyuan Zhang², Junyi Gong², Huan Wang¹, Lingyu Zhai¹, Dongfeng Dang³, Qian Liu⁴, Zheng Zhao² zhaozheng@cuhk.edu.cn, Ben Zhong Tang^2,5 tangbenz@cuhk.edu.cn

المصدر: Chemical Communications. 6/11/2024, Vol. 60 Issue 46, p5960-5963. 4p.

مصطلحات موضوعية: *METHICILLIN-resistant staphylococcus aureus, *STAPHYLOCOCCUS aureus infections, *GRAM-negative bacteria, *GRAM-positive bacteria

مستخلص: A cationic aggregation-induced emission photosensitizer (AIE-PS) MNNPyBB has been reported to have antibacterial effects against both Gram-positive and Gram-negative bacteria. The bacterial kill mechanism has been investigated and elucidated. In a methicillin-resistant Staphylococcus aureus subcutaneous infection model, wound closure has been achieved with normal re-epithelialization and preserved skin morphology [ABSTRACT FROM AUTHOR]

المؤلفون: Beshiru, Abeni^1,2 (AUTHOR), Igbinosa, Isoken H.^1,3 (AUTHOR), Akinnibosun, Olajide^1,4 (AUTHOR), Ogofure, Abraham G.¹ (AUTHOR), Dunkwu-Okafor, Afamefuna¹ (AUTHOR), Uwhuba, Kate E.² (AUTHOR), Igbinosa, Etinosa O.¹ (AUTHOR) Etinosa.Igbinosa@uniben.edu

المصدر: Scientific Reports. 6/9/2024, Vol. 14 Issue 1, p1-11. 11p.

مصطلحات موضوعية: *METHICILLIN-resistant staphylococcus aureus, *STAPHYLOCOCCAL diseases, *STAPHYLOCOCCUS aureus, *POLYMERASE chain reaction, *MULTIDRUG resistance

مصطلحات جغرافية: EDO State (Nigeria), NIGERIA

مستخلص: The study investigated the economic concerns associated with livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in livestock (cow), examining its connection to severe infections, antimicrobial resistance (AMR), and virulence factors. The research, conducted in Edo State, Nigeria, analyzed 400 samples (200 rectal and 200 nasal swabs) collected between March 2018 and February 2019. MRSA prevalence was identified using conventional culture-based methods and polymerase chain reaction (PCR) techniques, revealing 63.5% (n = 254) for Staphylococcus aureus and 55% (n = 220) for MRSA. Of the 76 mecA-positive MRSA isolates, 64.5% (n = 49) exhibited multidrug resistance (MDR) while the remaining were sensitive to specific antimicrobials. Key virulence genes, such as PVL (81.6%; n = 62) and tsst-1 (44.7%; n = 34), were prevalent, along with AMR genes like mecC, tetM, ermA, ermC, vanA, and vanC. Staphylococcal chromosomal cassette mec (SCCmec) typing identified different types, notably II, IVa, and IVb. Biofilm formation, a crucial virulence factor varied in strength, is associated with icaA and icaB genes (p < 0.01). The findings highlighted substantial AMR and biofilm-forming capacity within LA-MRSA isolates, emphasizing the importance of ongoing surveillance for informed treatment strategies, AMR policies, and control measures against MDR staphylococcal infections. [ABSTRACT FROM AUTHOR]

المؤلفون: Cullum, Emily^1,2 (AUTHOR), Perez-Betancourt, Yunys^1,3 (AUTHOR), Shi, Miaomiao^1,3 (AUTHOR), Gkika, Eirinaios¹ (AUTHOR), Schneewind, Olaf¹ (AUTHOR), Missiakas, Dominique^1,3 (AUTHOR) dmissiak@bsd.uchicago.edu, Golovkina, Tatyana^1,2,4,5 (AUTHOR) dmissiak@bsd.uchicago.edu

المصدر: PLoS Pathogens. 6/6/2024, Vol. 20 Issue 6, p1-18. 18p.

مصطلحات موضوعية: *STAPHYLOCOCCUS aureus, *T cells, *BACTERIAL colonies, *HISTOCOMPATIBILITY, *METHICILLIN-resistant staphylococcus aureus, *SOFT tissue infections, *B cells, *DISEASE relapse

مستخلص: Staphylococcus aureus is a human-adapted pathogen that replicates by asymptomatically colonizing its host. S. aureus is also the causative agent of purulent skin and soft tissue infections as well as bloodstream infections that result in the metastatic seeding of abscess lesions in all organ tissues. Prolonged colonization, infection, disease relapse, and recurrence point to the versatile capacity of S. aureus to bypass innate and adaptive immune defenses as well as the notion that some hosts fail to generate protective immune responses. Here, we find a genetic trait that provides protection against this pathogen. Mice lacking functional H2-O, the equivalent of human HLA-DO, inoculated with a mouse-adapted strain of S. aureus, efficiently decolonize the pathogen. Further, these decolonized animals resist subsequent bloodstream challenge with methicillin-resistant S. aureus. A genetic approach demonstrates that T-cell dependent B cell responses are required to control S. aureus colonization and infection in H2-O-deficient mice. Reduced bacterial burdens in these animals correlate with increased titers and enhanced phagocytic activity of S. aureus-specific antibodies. H2-O negatively regulates the loading of high affinity peptides on major histocompatibility class II (MHC-II) molecules. Thus, we hypothesize that immune responses against S. aureus are derepressed in mice lacking H2-O because more high affinity peptides are presented by MHC-II. We speculate that loss-of-function HLA-DO alleles may similarly control S. aureus replication in humans. Author summary: Humans develop antibodies upon exposure to Staphylococcus aureus but seroconversion does not necessarily protect against invasive diseases or their recurrence as documented by the complexity in treating such infections both in hospitals and communities. Colonization constitutes the highest risk factor for disease-causing infections. Yet, the number of infections is relatively low considering that all newborns are exposed to S. aureus at birth and the bacterium continues to colonize the nares of about a third of the adult population. Here we show that changes in the major histocompatibility class II (MHC-II) pathway that selects pathogen-specific antigens, result in enhanced protective immune responses against S. aureus in animals. We speculate that specific alleles of the genes involved in the MHC-II pathway may underlie a range of protective immune responses such that not all individuals exposed to S. aureus are at the same risk for infection. [ABSTRACT FROM AUTHOR]

المؤلفون: Traoré, Roukiatou^1,2 (AUTHOR), Ouédraogo, Ganamé Abasse¹ (AUTHOR) ganamabasse@gmail.com, Ouédraogo, Abdoul Salam³ (AUTHOR), Savadogo, Aly¹ (AUTHOR), Zongo, Cheikna¹ (AUTHOR), Godreuil, Sylvain² (AUTHOR)

المصدر: BMC Research Notes. 6/3/2024, Vol. 17 Issue 1, p1-7. 7p.

مصطلحات موضوعية: *STAPHYLOCOCCUS aureus, *DRUG resistance in bacteria, *MOLECULAR epidemiology, *METHICILLIN-resistant staphylococcus aureus, *AGAR, *TOXINS, *MACROLIDE antibiotics, *FLUIDS

مصطلحات جغرافية: BURKINA Faso

مستخلص: Staphylococcus aureus is a pathogen with high epidemic potential frequently involved in nosocomials and communities infections. The pathogenicity of Staphylococcus aureus is due to both its ability to resist antibiotics and to Produce toxins. This work aims at studying the resistance and Molecular Epidemiology of Staphylococcus aureus. Antibiotic susceptibility of the 70 strains isolates of Staphylococcus aureus was determined by agar diffusion while Multiplex PCR and MLST were used to search toxin-coding genes and MRSA typing, respectively. 14.28% of isolates were multidrug resistant. Staphylococcus aureus showed high susceptibility to aminoglycoside and Macrolides familly. lukS-PV/lukF-PV and sea genes were detected in 45% and 3% of Staphylococcus aureus respectively. Ten (10) sequence types including ST5710, ST2430, ST5289, ST5786, ST6942, ST6943, ST6944, ST6945, ST6946, ST6947 have been reported. The study showed a diversity of antibiotic resistance phenotypes and a great diversity of MRSA clones causing infections. [ABSTRACT FROM AUTHOR]