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1.
ACS Sustain Chem Eng ; 12(8): 3243-3255, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38425833

RESUMEN

Plastics' long degradation time and their role in adding millions of metric tons of plastic waste to our oceans annually present an acute environmental challenge. Handling end-of-life waste from wind turbine blades (WTBs) is equally pressing. Currently, WTB waste often finds its way into landfills, emphasizing the need for recycling and sustainable solutions. Mechanical recycling of composite WTB presents an avenue for the recovery of glass fibers (GF) for repurposing as fillers or reinforcements. The resulting composite materials exhibit improved properties compared to the pure PAN polymer. Through the employment of the dry-jet wet spinning technique, we have successfully manufactured PAN/GF coaxial-layered fibers with a 0.1 wt % GF content in the middle layer. These fibers demonstrate enhanced mechanical properties and a lightweight nature. Most notably, the composite fiber demonstrates a significant 24.4% increase in strength and a 17.7% increase in modulus. These fibers hold vast potential for various industrial applications, particularly in the production of structural components (e.g., electric vehicles), contributing to enhanced performance and energy efficiency.

2.
Reprod Dev Med ; 8(1): 61-65, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38404366

RESUMEN

The uterus is transiently receptive for embryo implantation. It remains to be understood why the uterus does not reject a semi-allogeneic embryo (to the biological mother) or an allogeneic embryo (to a surrogate) for implantation. To gain insights, we examined uterine early response genes approaching embryo attachment on day 3 post coitum (D3) at 22 hours when blue dye reaction, an indication of embryo attachment, had not manifested in mice. C57BL/6 pseudo-pregnant (control) and pregnant mouse uteri were collected on D3 at 22 hours for microarray analysis. The self-assembling-manifold (SAM) algorithm identified 21,858 unique probesets. Principal component analysis indicated a clear separation between the pseudo-pregnant and pregnant groups. There were 106 upregulated and five downregulated protein-coding genes in the pregnant uterus with fold change (fc) >1.5 and q value <5%. Gene ontology (GO) analysis of the 106 upregulated genes revealed 38 significant GO biological process (GOBP) terms (P <0.05), and 32 (84%) of them were associated with immune responses, with a dominant natural killer (NK) cell activation signature. Among the top eight upregulated protein-coding genes, Cyp26a1 inactivates retinoic acid (RA) while Lrat promotes vitamin A storage, both of which are expected to attenuate RA bioavailability; Atp6v0d2 and Gjb2 play roles in ion transport and transmembrane transport; Gzmb, Gzmc, and Il2rb are involved in immune responses; and Tdo2 is important for kynurenine pathway. Most of these genes or their related pathways have functions in immune regulations. RA signaling has been implicated in immune tolerance and immune homeostasis, and uterine NK cells have been implicated in immunotolerance at the maternal-fetal interface in the placenta. The mechanisms of immune responses approaching embryo attachment remain to be elucidated. The coordinated effects of the early response genes may hold the keys to the question of why the uterus does not reject an implanting embryo.

3.
Ann Plast Surg ; 92(4): 447-456, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38319959

RESUMEN

BACKGROUND: Some surgeons use body mass index criteria within the patient selection processes before vaginoplasty, thereby limiting access to select obese patients. We sought to better characterize the effect of obesity on postoperative outcomes across multiple vaginoplasty techniques. METHODS: A single-center retrospective review of all transfeminine patients undergoing primary vaginoplasty procedures from December 2018 to July 2022 was conducted. Patients were stratified into cohorts according to the World Health Organization Obesity Class criteria. Data regarding demographics, comorbidities, operative details, postoperative complications, and all-cause revision were collected. RESULTS: A total of 237 patients met the inclusion criteria. Average follow-up duration was 9.1 ± 4.7 months. Multivariate regression revealed that patients with class I and class II/III obesity were associated with higher odds of developing vaginal stenosis (class I: odds ratio [OR], 7.1 [ P = 0.003]; class II/III: OR, 3.4 [ P = 0.018]) and all-cause revision (class I: OR, 3.7 [ P = 0.021]; class II/III: OR, 4.8 [ P = 0.027]). Undergoing either robotic peritoneal or robotic intestinal vaginoplasty was associated with lower odds of delayed wound healing (peritoneal: OR, 0.2 [ P < 0.001]; intestinal: OR, 0.2 [ P = 0.011]). Lastly, adherence to dilation regimen was negatively associated with development of vaginal stenosis (OR, 0.04; P < 0.001). CONCLUSIONS: Patients with obesity may be at a higher risk of developing vaginal stenosis after vaginoplasty, which may ultimately necessitate operative revision. Although patients with obesity may remain surgical candidates, proper preoperative counseling and adherence to postoperative vaginal dilation regimens are critical to optimizing outcomes.


Asunto(s)
Transexualidad , Vagina , Humanos , Femenino , Vagina/cirugía , Constricción Patológica , Obesidad/complicaciones , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
4.
iScience ; 26(6): 106789, 2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37213232

RESUMEN

Delivery of pharmaceutical therapeutics to the inner ear to treat and prevent hearing loss is challenging. Systemic delivery is not effective as only a small fraction of the therapeutic agent reaches the inner ear. Invasive surgeries to inject through the round window membrane (RWM) or cochleostomy may cause damage to the inner ear. An alternative approach is to administer drugs into the middle ear using an intratympanic injection, with the drugs primarily passing through the RWM to the inner ear. However, the RWM is a barrier, only permeable to a small number of molecules. To study and enhance the RWM permeability, we developed an ex vivo porcine RWM model, similar in structure and thickness to the human RWM. The model is viable for days, and drug passage can be measured at multiple time points. This model provides a straightforward approach to developing effective and non-invasive delivery methods to the inner ear.

5.
Laryngoscope Investig Otolaryngol ; 8(2): 584-590, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37090864

RESUMEN

Objective: We aimed to determine the rate of complications associated with autologous costal cartilage graft harvest for pediatric laryngotracheal reconstruction (LTR). Secondarily, we sought to identify risk factors associated with the harvest of autologous costal cartilage, as well as evaluate management strategies. Data Sources: An electronic database search of Ovid MEDLINE, Ovid EMBASE, and PubMed was completed for articles pertaining to complications in autologous costal cartilage harvest for pediatric LTR. Review Methods: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The study characteristics, operative information, and patient demographics were collected. The data concerning postoperative complications, risk factors, and management strategies were collected and analyzed for patterns. Results: A total of 31 manuscripts representing 745 patients were included for analysis. The reported donor site complications included pneumothorax (n = 13, 1.74%), pleural tear (n = 5, 0.67%), infection (n = 8, 1.07%), and scar-related problems (n = 2, 0.26%). There were no reported cases of seroma, persistent pain, or chest wall deformity. Only five studies discussed the management of donor site complications, with intervention in 11 (39.28%) patients including chest tube drainage and steroid injection. Conclusion: There is significant variability in the literature regarding complication rates in autologous costal cartilage harvest for pediatric LTR. The incidence of major postoperative complications is low and supports the use of autologous costal cartilage as graft material for pediatric LTR. Level of Evidence: NA.

6.
Biol Reprod ; 108(3): 359-362, 2023 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-36611017

RESUMEN

Forkhead box protein A2 (FOXA2) is a pioneer transcription factor important for epithelial budding and morphogenesis in different organs. It has been used as a specific marker for uterine glandular epithelial cells (GE). FOXA2 has close interactions with estrogen receptor α (ERα). ERα binding to Foxa2 gene in the uterus indicates its regulation of Foxa2. The intimate interactions between ERα and FOXA2 and their essential roles in early pregnancy led us to investigate the expression of FOXA2 in the female reproductive tract of pre-implantation epiERα-/- (Esr1fl/flWnt7aCre/+) mice, in which ERα is conditionally deleted in the epithelium of reproductive tract. In the oviduct, FOXA2 is detected in the ciliated epithelial cells of ampulla but absent in the isthmus of day 3.5 post-coitum (D3.5) Esr1fl/fl control and epiERα-/- mice. In the uterus, FOXA2 expression in the GE appears to be comparable between Esr1fl/fl and epiERα-/- mice. However, FOXA2 is upregulated in the D0.5 and D3.5 but not PND25-28 epiERα-/- uterine luminal epithelial cells (LE). In the vagina, FOXA2 expression is low in the basal layer and increases toward the superficial layer of the D3.5 Esr1fl/fl vaginal epithelium, but FOXA2 is detected in the basal, intermediate, and superficial layers, with the strongest FOXA2 expression in the intermediate layers of the D3.5 epiERα-/- vaginal epithelium. This study demonstrates that loss of ERα in LE and vaginal basal layer upregulates FOXA2 expression in these epithelial cells during early pregnancy. The mechanisms for epithelial cell-type specific regulation of FOXA2 by ERα remain to be elucidated.


Asunto(s)
Receptor alfa de Estrógeno , Útero , Animales , Femenino , Ratones , Embarazo , Epitelio/metabolismo , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Factor Nuclear 3-beta del Hepatocito/genética , Factor Nuclear 3-beta del Hepatocito/metabolismo , Regulación hacia Arriba , Útero/metabolismo , Vagina/metabolismo
7.
Biol Reprod ; 108(2): 204-217, 2023 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-36308434

RESUMEN

Uterine fluid plays important roles in supporting early pregnancy events and its timely absorption is critical for embryo implantation. In mice, its volume is maximum on day 0.5 post-coitum (D0.5) and approaches minimum upon embryo attachment ~D4.0. Its secretion and absorption in ovariectomized rodents were shown to be promoted by estrogen and progesterone (P4), respectively. The temporal mechanisms in preimplantation uterine fluid absorption remain to be elucidated. We have established an approach using intraluminally injected Alexa Fluor™ 488 Hydrazide (AH) in preimplantation control (RhoAf/f) and P4-deficient RhoAf/fPgrCre/+ mice. In control mice, bulk entry (seen as smeared cellular staining) via uterine luminal epithelium (LE) decreases from D0.5 to D3.5. In P4-deficient RhoAf/fPgrCre/+ mice, bulk entry on D0.5 and D3.5 is impaired. Exogenous P4 treatment on D1.5 and D2.5 increases bulk entry in D3.5 P4-deficient RhoAf/fPgrCre/+ LE, while progesterone receptor (PR) antagonist RU486 treatment on D1.5 and D2.5 diminishes bulk entry in D3.5 control LE. The abundance of autofluorescent apical fine dots, presumptively endocytic vesicles to reflect endocytosis, in the LE cells is generally increased from D0.5 to D3.5 but its regulation by exogenous P4 or RU486 is not obvious under our experimental setting. In the glandular epithelium (GE), bulk entry is rarely observed and green cellular dots do not show any consistent differences among all the investigated conditions. This study demonstrates the dominant role of LE but not GE, the temporal mechanisms of bulk entry and endocytosis in the LE, and the inhibitory effects of P4-deficiency and RU486 on bulk entry in the LE in preimplantation uterine fluid absorption.


Asunto(s)
Implantación del Embrión , Mifepristona , Embarazo , Femenino , Animales , Ratones , Mifepristona/farmacología , Implantación del Embrión/fisiología , Progesterona/farmacología , Estrógenos/farmacología , Útero/fisiología , Roedores
8.
JAAD Case Rep ; 27: 64-66, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35818536
10.
PLoS One ; 16(11): e0259415, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34723972

RESUMEN

Recent avian influenza infection outbreaks have resulted in global biosecurity and economic concerns. Mallards are asymptomatic for the disease and can potentially spread AI along migratory bird flyways. In a previous study, trained mice correctly discriminated the health status of individual ducks on the basis of fecal odors when feces from post-infection periods were paired with feces from pre-infection periods. Chemical analyses indicated that avian influenza infection was associated with a marked increase of acetoin (3-hydroxy-2-butanone) in feces. In the current study, domesticated male ferrets (Mustela putorius furo) were trained to display a specific conditioned response (i.e. active scratch alert) in response to a marked increase of acetoin in a presentation of an acetoin:1-octen-3-ol solution. Ferrets rapidly generalized this learned response to the odor of irradiated feces from avian influenza infected mallards. These results suggest that a trained mammalian biosensor could be employed in an avian influenza surveillance program.


Asunto(s)
Hurones , Animales , Ratones , Odorantes
12.
BMC Med ; 19(1): 46, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33618741

RESUMEN

BACKGROUND: Following the initial identification of the 2019 coronavirus disease (covid-19), the subsequent months saw substantial increases in published biomedical research. Concerns have been raised in both scientific and lay press around the quality of some of this research. We assessed clinical research from major clinical journals, comparing methodological and reporting quality of covid-19 papers published in the first wave (here defined as December 2019 to May 2020 inclusive) of the viral pandemic with non-covid papers published at the same time. METHODS: We reviewed research publications (print and online) from The BMJ, Journal of the American Medical Association (JAMA), The Lancet, and New England Journal of Medicine, from first publication of a covid-19 research paper (February 2020) to May 2020 inclusive. Paired reviewers were randomly allocated to extract data on methodological quality (risk of bias) and reporting quality (adherence to reporting guidance) from each paper using validated assessment tools. A random 10% of papers were assessed by a third, independent rater. Overall methodological quality for each paper was rated high, low or unclear. Reporting quality was described as percentage of total items reported. RESULTS: From 168 research papers, 165 were eligible, including 54 (33%) papers with a covid-19 focus. For methodological quality, 18 (33%) covid-19 papers and 83 (73%) non-covid papers were rated as low risk of bias, OR 6.32 (95%CI 2.85 to 14.00). The difference in quality was maintained after adjusting for publication date, results, funding, study design, journal and raters (OR 6.09 (95%CI 2.09 to 17.72)). For reporting quality, adherence to reporting guidelines was poorer for covid-19 papers, mean percentage of total items reported 72% (95%CI:66 to 77) for covid-19 papers and 84% (95%CI:81 to 87) for non-covid. CONCLUSIONS: Across various measures, we have demonstrated that covid-19 research from the first wave of the pandemic was potentially of lower quality than contemporaneous non-covid research. While some differences may be an inevitable consequence of conducting research during a viral pandemic, poor reporting should not be accepted.


Asunto(s)
COVID-19/epidemiología , Publicaciones Periódicas como Asunto/normas , Calidad de la Atención de Salud/normas , Investigación Biomédica , Humanos , Proyectos de Investigación/normas , Informe de Investigación
13.
Sci Adv ; 4(8): eaar4644, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30167459

RESUMEN

The world is urbanizing quickly with nearly 4 billion people presently living in urban areas, about 1 billion of them in slums. Achieving sustainable development from rapid urbanization relies critically on creating cities without slums. We show that it is possible to diagnose systematically the central physical problem of slums-the lack of spatial accesses and related services-using a topological analysis of neighborhood maps and resolved by finding solutions to a sequence of constrained optimization problems. We set up the problem by showing that the built environment of any city can be decomposed into two types of networked spaces-accesses and places-and prove that these spaces display universal topological characteristics. We then show that while the neighborhoods of developed cities express the same common topology, urban slums fall into a different topological class. We demonstrate that it is always possible to find solutions that grow a street network in existing slums, providing universal accesses at minimal disruption and cost. We then show how elaborations of this procedure that include local preferences and reduce travel distances between places result from additional access construction. These methods are presently taking effect in neighborhoods in Cape Town (South Africa) and Mumbai (India), demonstrating their practical feasibility and emphasizing their role as a platform to enable communities and local governments to combine technical knowledge with local aspirations into contextually appropriate urban sustainable development solutions.

14.
Case Rep Infect Dis ; 2018: 3685439, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29977632

RESUMEN

Myiasis is the infestation by dipterous fly larvae in humans and animals. The larvae can infect living or necrotic tissue involving the skin, nasopharynx, genitourinary, and gastrointestinal tracts. The accidental ingestion of eggs causes infection of the intestinal tract. We report a case of intestinal myiasis caused by Sarcophaga spp. larvae in a two-year-old child from Limatambo province in the Cusco region of Peru. Live larvae were identified incidentally in this child's stool sample during the study screening for Strongyloides stercoralis. The child did not have any constitutional or abdominal symptoms. The morphological examination of the specimen under magnification revealed Sarcophaga spp. larvae. We performed a literature review of publications reporting intestinal myiasis caused by Sarcophaga spp. and discussed key aspects of this infestation.

15.
Biochimie ; 145: 137-144, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28838608

RESUMEN

We have developed a new cocaine-binding aptamer variant that has a significantly higher melt temperature when bound to a ligand than the currently used sequence. Retained in this new construct is the ligand-induced structure-switching binding mechanism that is important in biosensing applications of the cocaine-binding aptamer. Isothermal titration calorimetry methods show that the binding affinity of this new sequence is slightly tighter than the existing cocaine-binding aptamer. The improved thermal performance, a Tm increase of 4 °C for the cocaine-bound aptamer and 9 °C for the quinine-bound aptamer, was achieved by optimizing the DNA sequence in stem 2 of the aptamer to have the highest stability based on the nearest neighbor thermodynamic parameters and confirmed by UV and fluorescence spectroscopy. The sequences in stem 1 and stem 3 were unchanged in order to retain the structure switching and ligand binding functions. The more favorable thermal stability characteristics of the OR3 aptamer should make it a useful construct for sensing applications employing the cocaine-binding aptamer system.


Asunto(s)
Aptámeros de Nucleótidos/química , Cocaína/química , Conformación de Ácido Nucleico , Calorimetría/métodos , Cocaína/análisis
16.
Adv Ther (Weinh) ; 1(3)2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31544132

RESUMEN

In the last decade, the use of microRNA (miRNA) and extracellular vesicle (EV) therapies has emerged as an alternative approach to mitigate the negative effects of several disease pathologies ranging from cancer to tissue and organ regeneration; however, delivery approaches towards target tissues have not been optimized. To alleviate these challenges, including rapid diffusion upon injection and susceptibility to degradation, porcine-derived decellularized extracellular matrix (ECM) hydrogels are examined as a potential delivery platform for miRNA and EV therapeutics. The incorporation of EVs and miRNA antagonists, including anti-miR and antago-miR, in ECM hydrogels results in a prolonged release as compared to the biologic agents alone. In addition, individual in vitro assessments confirm the bioactivity of the therapeutics upon release from the ECM hydrogels. This work demonstrates the feasibility of encapsulating miRNA and EV therapeutics in ECM hydrogels to enhance delivery and potentially efficacy in later in vivo applications.

17.
ACS Sens ; 2(10): 1539-1545, 2017 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-28929744

RESUMEN

Understanding how aptamer structure and function are related is crucial in the design and development of aptamer-based biosensors. We have analyzed a series of cocaine-binding aptamers with different lengths of their stem 1 in order to understand the role that this stem plays in the ligand-induced structure-switching binding mechanism utilized in many of the sensor applications of this aptamer. In the cocaine-binding aptamer, the length of stem 1 controls whether the structure-switching binding mechanism for this aptamer occurs or not. We varied the length of stem 1 from being one to seven base pairs long and found that the structural transition from unfolded to folded in the unbound aptamer is when the aptamer elongates from 3 to 4 base pairs in stem 1. We then used this knowledge to achieve new binding selectivity of this aptamer for quinine over cocaine by using an aptamer with a stem 1 two base pairs long. This selectivity is achieved by means of the greater affinity quinine has for the aptamer compared with cocaine. Quinine provides enough free energy to both fold and bind the 2-base pair-long aptamer while cocaine does not. This tuning of binding selectivity of an aptamer by reducing its stability is likely a general mechanism that could be used to tune aptamer specificity for tighter binding ligands.


Asunto(s)
Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Cocaína/química , Conformación de Ácido Nucleico , Quinina/química , Aptámeros de Nucleótidos/metabolismo , Sitios de Unión , Cocaína/metabolismo , Humanos , Ligandos , Quinina/metabolismo , Termodinámica
18.
Microb Pathog ; 93: 204-12, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26945561

RESUMEN

The genus Edwardsiella consists of bacteria with an intrinsic resistance to cyclic cationic antimicrobial peptides (CAMPs). Edwardsiella ictaluri, a pathogen of the catfish (Ictalurus punctatus) and the causative agent of a systemic infection, is highly resistant to CAMPs. Previously, we determined that the oligo-polysaccharide (O-PS) of the lipopolysaccharide (LPS) does not play a role in the E. ictaluri CAMP resistance and an intact core-lipid A structure is necessary for CAMPs resistance. Here, we evaluated the influence of the outer-core in the CAMPs resistance and fish virulence. E. ictaluri wabG, a gene that encodes for the UDP-glucuronic acid transferase that links the lipid A-inner-core to the outer-core-oligopolysaccharides, was deleted. Deletion of ΔwabG caused a pleiotropic effect, influencing LPS synthesis, CAMPs resistance, growth, and biofilm formation. E. ictaluri ΔwabG was attenuated in zebrafish indicating the important role of LPS during fish pathogenesis. Also, we evaluated the inflammatory effects of wabG LPS in catfish ligated loop model, showing a decreased inflammatory effect at the gut level respects to the E. ictaluri wild type. We conclude that E. ictaluri CAMPs resistance is related to the molecules present in the LPS outer-core and that fish gut inflammation triggered by E. ictaluri is LPS dependent, reinforcing the hypothesis that fish gut recognizes LPS in an O-PS dependent fashion.


Asunto(s)
Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Proteínas de la Membrana Bacteriana Externa/metabolismo , Edwardsiella ictaluri/metabolismo , Edwardsiella ictaluri/patogenicidad , Infecciones por Enterobacteriaceae/veterinaria , Enfermedades de los Peces/microbiología , Lipopolisacáridos/metabolismo , Secuencia de Aminoácidos , Animales , Proteínas de la Membrana Bacteriana Externa/química , Proteínas de la Membrana Bacteriana Externa/genética , Edwardsiella ictaluri/efectos de los fármacos , Edwardsiella ictaluri/genética , Infecciones por Enterobacteriaceae/microbiología , Ictaluridae , Datos de Secuencia Molecular , Alineación de Secuencia , Virulencia , Pez Cebra
19.
Infect Immun ; 82(8): 3394-404, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24866806

RESUMEN

Bacterial lipopolysaccharides (LPS) are structural components of the outer membranes of Gram-negative bacteria and also are potent inducers of inflammation in mammals. Higher vertebrates are extremely sensitive to LPS, but lower vertebrates, like fish, are resistant to their systemic toxic effects. However, the effects of LPS on the fish intestinal mucosa remain unknown. Edwardsiella ictaluri is a primitive member of the Enterobacteriaceae family that causes enteric septicemia in channel catfish (Ictalurus punctatus). E. ictaluri infects and colonizes deep lymphoid tissues upon oral or immersion infection. Both gut and olfactory organs are the primary sites of invasion. At the systemic level, E. ictaluri pathogenesis is relatively well characterized, but our knowledge about E. ictaluri intestinal interaction is limited. Recently, we observed that E. ictaluri oligo-polysaccharide (O-PS) LPS mutants have differential effects on the intestinal epithelia of orally inoculated catfish. Here we evaluate the effects of E. ictaluri O-PS LPS mutants by using a novel catfish intestinal loop model and compare it to the rabbit ileal loop model inoculated with Salmonella enterica serovar Typhimurium LPS. We found evident differences in rabbit ileal loop and catfish ileal loop responses to E. ictaluri and S. Typhimurium LPS. We determined that catfish respond to E. ictaluri LPS but not to S. Typhimurium LPS. We also determined that E. ictaluri inhibits cytokine production and induces disruption of the intestinal fish epithelia in an O-PS-dependent fashion. The E. ictaluri wild type and ΔwibT LPS mutant caused intestinal tissue damage and inhibited proinflammatory cytokine synthesis, in contrast to E. ictaluri Δgne and Δugd LPS mutants. We concluded that the E. ictaluri O-PS subunits play a major role during pathogenesis, since they influence the recognition of the LPS by the intestinal mucosal immune system of the catfish. The LPS structure of E. ictaluri mutants is needed to understand the mechanism of interaction.


Asunto(s)
Edwardsiella ictaluri/inmunología , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/patología , Lipopolisacáridos/inmunología , Lipopolisacáridos/toxicidad , Animales , Bagres , Edwardsiella ictaluri/genética , Inflamación , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Lipopolisacáridos/biosíntesis , Lipopolisacáridos/genética , Mutación
20.
Microbiology (Reading) ; 159(Pt 7): 1471-1486, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23676433

RESUMEN

The genus Edwardsiella comprises a genetically distinct taxon related to other members of the family Enterobacteriaceae. It consists of bacteria differing strongly in their biochemical and physiological features, natural habitats, and pathogenic properties. Intrinsic resistance to cationic antimicrobial peptides (CAMPs) is a specific property of the genus Edwardsiella. In particular, Edwardsiella ictaluri, an important pathogen of the catfish (Ictalurus punctatus) aquaculture and the causative agent of a fatal systemic infection, is highly resistant to CAMPs. E. ictaluri mechanisms of resistance to CAMPs are unknown. We hypothesized that E. ictaluri lipopolysaccharide (LPS) plays a role in both virulence and resistance to CAMPs. The putative genes related to LPS oligo-polysaccharide (O-PS) synthesis were in-frame deleted. Individual deletions of wibT, gne and ugd eliminated synthesis of the O-PS, causing auto-agglutination, rough colonies, biofilm-like formation and motility defects. Deletion of ugd, the gene that encodes the UDP-glucose dehydrogenase enzyme responsible for synthesis of UDP-glucuronic acid, causes sensitivity to CAMPs, indicating that UDP-glucuronic acid and its derivatives are related to CAMP intrinsic resistance. E. ictaluri OP-S mutants showed different levels of attenuation, colonization of lymphoid tissues and immune protection in zebrafish (Danio rerio) and catfish. Orally inoculated catfish with O-PS mutant strains presented different degrees of gut inflammation and colonization of lymphoid tissues. Here we conclude that intrinsic resistance to CAMPs is mediated by Ugd enzyme, which has a pleiotropic effect in E. ictaluri influencing LPS synthesis, motility, agglutination, fish gut inflammation and virulence.


Asunto(s)
Péptidos Catiónicos Antimicrobianos/farmacología , Bagres/microbiología , Farmacorresistencia Bacteriana , Edwardsiella ictaluri/efectos de los fármacos , Edwardsiella ictaluri/patogenicidad , Infecciones por Enterobacteriaceae/veterinaria , Enfermedades de los Peces/microbiología , Uridina Difosfato Glucosa Deshidrogenasa/metabolismo , Animales , Acuicultura , Edwardsiella ictaluri/enzimología , Edwardsiella ictaluri/genética , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Enterobacteriaceae/microbiología , Enfermedades de los Peces/inmunología , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/microbiología , Inflamación/inmunología , Inflamación/microbiología , Uridina Difosfato Glucosa Deshidrogenasa/genética , Virulencia
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