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1.
Artículo en Inglés | MEDLINE | ID: mdl-39360533

RESUMEN

INTRODUCTION: The concurrent presence of helminthiasis and bacterial diseases imposes a dual burden, worsening the challenges associated with each condition independently. This cohabitation intensifies the economic impact, creating a compounding effect on public health and economic well-being. METHOD: Phytochemical analysis of Cassia alata Extract (CAE) using infrared spectroscopy has revealed the presence of various functional groups. In addition, GC mass analysis has confirmed the presence of 26 active compounds. An assessment of the anthelmintic activity of CAE against mature earthworms has demonstrated comparable efficacy to the conventional anthelmintic, albendazole. The optimal dosage of 500 mg/ml has induced a rapid onset of paralysis (2.7 ± 0.5 min) and death (20.1 ± 1.7 min), outperforming albendazole (20 mg/mL) in terms of faster paralysis and death times (21.8 ± 1.1 and 30.14 ± 3.2 min, respectively). Structural modifications induced by CAE have been observed through light microscopy and Scanning Electron Microscopy (SEM). Control worms have exhibited normal body architecture, while CAE-treated worms have displayed size reduction, uniform body wall shrinkage, and increased cuticular thickness. Similar alterations have been observed in albendazole-treated worms. RESULTS: The antibacterial activity of CAE has been evaluated through a broth dilution assay, which has revealed a dose-response effect. At 6.25 mg/ml, CAE has exhibited 100% inhibitory action against both Gram-positive and Gram-negative bacteria. Significant differences in bacterial viability have been noted at lower concentrations, with no significant variation at 0.3906 mg/ml of CAE. CONCLUSION: The findings have highlighted the multifaceted bioactivity of CAE, showcasing its potential as an anthelmintic agent and antimicrobial agent against a spectrum of bacterial strains. The observed structural alterations in treated worms have provided insights into the potential mechanisms underlying the anthelmintic effects.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39365412

RESUMEN

In 2019, Pantoea piersonii was initially isolated from the interior surfaces of the International Space Station. This microorganism is a species within the genus Pantoea in the family Erwiniaceae, belonging to the order Enterobacterales. Recent literature has documented four cases of its isolation. Despite initial predictions suggesting the non-pathogenicity of P. piersonii strains, evidence from observed cases indicates potential pathogenicity. According to documented evidence in the literature, this microorganism is capable of causing severe and life-threatening conditions, including sepsis. Traditional tests, as well as automated systems, may fail to provide complete differentiation due to these similarities. While MALDI-TOF MS is a valuable tool for identification in clinical diagnostic microbiology, sequencing may be necessary for precise identification. To determine the antibiotic susceptibility profile, various methods can be utilized, including minimum inhibitory concentration determination, disk diffusion testing (Kirby-Bauer test), genotypic resistance assays (PCR and sequencing), and automated systems. The literature reports a limited number of cases associating P. piersonii with human infection. This study contributes to this body of knowledge by reporting a novel case in which P. piersonii was isolated from a tissue sample for the first time. In this case report, the patient achieved recovery following the administration of appropriate antibiotic treatment based on the diagnosis. It underscores the need for precise identification and understanding of its pathogenicity.

3.
Front Immunol ; 15: 1457174, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39359730

RESUMEN

Background: Humoral bactericidal activity was first recognized nearly a century ago. However, the extent of inter-individual heterogeneity and the mechanisms underlying such heterogeneity beyond antibody or complement systems have not been well studied. Methods: The plasma bactericidal activity of five healthy volunteers were tested against 30 strains of Gram-negative uropathogens, Klebsiella pneumoniae and Escherichia coli, associated with bloodstream infections. IgG and IgM titers specific to K. pneumoniae strains KP13883 and KPB1 were measured by ELISA, and complement inhibitor was used to measure the contribution of complement-induced killing. Furthermore, MALDI-TOF mass spectrometry was conducted to determine the metabolomic components of plasma with bactericidal properties in 25 healthy individuals using Bayesian inference of Pearson correlation between peak intensity and colony counts of surviving bacteria. Results: Plasma bactericidal activity varied widely between individuals against various bacterial strains. While individual plasma with higher IgM titers specific to K. pneumoniae strain KP13883 showed more efficient killing of the strain, both IgM and IgG titers for K. pneumoniae strain KPB1 did not correlate well with the killing activity. Complement inhibition assays elucidated that the complement-mediated killing was not responsible for the inter-individual heterogeneity in either isolate. Subsequently, using MALDI-TOF mass spectrometry on plasmas of 25 healthy individuals, we identified several small molecules including gangliosides, pediocins, or saponins as candidates that showed negative correlation between peak intensities and colony forming units of the test bacteria. Conclusion: This is the first study to demonstrate the inter-individual heterogeneity of constitutive innate humoral bactericidal function quantitatively and that the heterogeneity can be independent of antibody or the complement system.


Asunto(s)
Anticuerpos Antibacterianos , Proteínas del Sistema Complemento , Inmunidad Humoral , Inmunoglobulina G , Inmunoglobulina M , Klebsiella pneumoniae , Humanos , Proteínas del Sistema Complemento/inmunología , Inmunoglobulina M/inmunología , Inmunoglobulina M/sangre , Klebsiella pneumoniae/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/sangre , Actividad Bactericida de la Sangre/inmunología , Adulto , Masculino , Femenino , Escherichia coli/inmunología , Persona de Mediana Edad , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
4.
Cureus ; 16(9): e68464, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39360101

RESUMEN

Stenotrophomonas maltophilia (S. maltophilia) is a rare, multi-drug-resistant opportunistic bacteria that typically causes serious infections in immunocompromised and hospitalized patients, often leading to fatal pneumonia or bacteremia. We present the case of a healthy 15-year-old immunocompetent female who developed severe oral ulcers due to S. maltophilia following a recent COVID-19 infection. To our knowledge, this is the first reported case of S. maltophilia manifesting in this manner after COVID-19. Scrapes from the oral lesions were collected and cultured, confirming the infection.The CBC and immunoglobulin reports revealed mildly elevated IgA and platelet levels, with no evidence of immunodeficiency.The patient was treated with trimethoprim/sulfamethoxazole (TMP-SMX) based on culture sensitivity, and she responded well to treatment. She was referred to an infectious disease specialist for further monitoring. COVID-19 has recently been implicated in many unusual presentations, associations, and syndromes. One of the most supported theories about COVID-19 is its association with a transient immunodeficient state or a generalized state of immune system dysregulation that can compromise both innate and adaptive immunity. This case supports that theory, as no other apparent etiology for such an otherwise opportunistic infection was identified. The recognition of such atypical infections in previously healthy individuals, particularly post COVID-19, highlights the importance of sharpening clinical vigilance and considering opportunistic pathogens in differential diagnoses. Further research is warranted to explore the potential link between COVID-19 and the susceptibility to rare opportunistic infections, which may guide future clinical practices.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39389125

RESUMEN

BACKGROUND: Acute exacerbations of chronic rhinosinusitis (AECRS) are commonly triggered by rhinovirus (RV) infections with secondary bacterial infections. Risk factors for AECRS are not well understood. OBJECTIVE: To determine if carriers of the minor allele rs6967330 (AA/AG) in the Cadherin related family member 3 (CDHR3) gene have an increased risk for RV infections in AECRS in vivo and identify CDHR3 genotype-dependent host responses to RV infection in differentiated nasal airway liquid interface (ALI) cultures ex vivo. METHODS: We performed a prospective year-long study of adult subjects with chronic rhinosinusitis (CRS) by rs6967330 genotype (AA/AG, n=16; GG, n=38). We contacted subjects every 2 weeks, and if they reported AECRS clinical data were collected. ALI cultures of adults with CRS (AG/AA,n=19; GG,n=19) were challenged with RV-A and RV-C. We measured viral copy numbers at 4- and 48-hours post-infection and RNA transcriptomes and cytokines at 48 hours post infection. RESULTS: Subjects with the minor allele had significantly higher rates of RV and bacterial infections than those with the major allele. ALI minor allele cultures had higher viral copy numbers of RV-A and RV-C after 48 hours compared to the major allele. Differentially expressed genes (DEG) and pathways identified an upregulation of IL-10 and IL4/13 pathways and a significant downregulation of toll like receptor (TLR) pathways in the minor allele cultures after RV-A and RV-C infection. Unsupervised hierarchical analysis of all DEGs suggest that allergic rhinitis had an additive effect on this response. CONCLUSIONS: The rs6967330 minor allele is associated with increased RV-A and RV-C replication, downregulation of TLR-mediated responses and increased T2-type and cytokine and chemokine responses during RV infection.

6.
Int J Biol Macromol ; : 136461, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39393743

RESUMEN

Novel strategy is urgently needed to overcome the bacterial infection all over the world due to unreasonable use of biotics. In recent years, nanozymes have attracted great interests of researchers for their high catalytic efficiency and biocompatibility. In this study, a novel multiple enzyme-mimic polypeptide-based carbon nanoparticle was synthesized by N-carboxyanhydride mediated ring opening polymerization (ROP) and Fe coordination for actualizing ROS regulation and photo-thermal therapy. The multiple enzyme-mimic activities of the nanozyme, such as peroxidase, oxidase, catalase, and glutathione peroxidase, were detailly explored in ROS regulation for potential utilization in bacterial inhibition. The photo-thermal effect of the nanozyme was investigated under 808 nm NIR irradiation. Enhanced inhibition rate of the as prepared nanozyme was observed against Gram-negative Escherichia coli (99.03 %) and Gram positive Staphylococcus aureus (99.78 %) planktonic bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) was chosen as the drug resistant bacteria model to evaluate the efficiency in bacterial biofilm disruption. Improved healing efficacy of 99.05 % against MRSA wound infection and excellent biosafety were observed in mice model experiments for the as prepared nanozyme. In conclusion, the as synthesized nanozyme with ROS regulation, enhanced bacteria inhibition, and excellent biocompatibility could be potentially applied in clinic against bacterial infection.

7.
BMC Infect Dis ; 24(1): 1109, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39370524

RESUMEN

PURPOSE: Acute necrotizing encephalopathy (ANE), a rare and severe brain disorder, is typically linked to prior infections. ANE predominantly affects children, with most reported cases attributed to viral infections. However, instances of bacterial-induced ANE are infrequent. Here, we present a case of adult-onset ANE associated with bacterial infection. CASE DESCRIPTIONS: The patient exhibited a hyperinflammatory state following a urinary tract bacterial infection, with neurological function rapidly declining into a coma as the illness progressed. Gram culture of blood suggested Escherichia coli infection. A magnetic resonance imaging (MRI) scan of the brain showed symmetrical hyperintense lesions involving bilateral thalami and pons in T2-weighted and fluid-attenuated inversion recovery images. These lesions also presented with diffuse cerebral edema and diffusion restriction and subacute hemorrhage. Based on clinical symptoms and typical brain MRI, ANE was diagnosed, and the patient underwent immunotherapy. CONCLUSIONS: This case underscores the occurrence of ANE triggered by bacterial infection, expanding our understanding of the pathogens associated with this condition. It suggests that ANE may be an immune-mediated disorder rather than solely an infectious disease.


Asunto(s)
Infecciones por Escherichia coli , Leucoencefalitis Hemorrágica Aguda , Imagen por Resonancia Magnética , Humanos , Leucoencefalitis Hemorrágica Aguda/diagnóstico , Leucoencefalitis Hemorrágica Aguda/patología , Leucoencefalitis Hemorrágica Aguda/microbiología , Infecciones por Escherichia coli/complicaciones , Infecciones por Escherichia coli/microbiología , Masculino , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Infecciones Urinarias/microbiología , Infecciones Urinarias/complicaciones , Escherichia coli/aislamiento & purificación , Femenino
8.
Vet Res Commun ; 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39373785

RESUMEN

Mandarin fish (Siniperca chuatsi) is a prominent freshwater species with significant economic value in China, while disease poses a major hindrance to the advancement of mandarin fish aquaculture. To date, the understanding of the prevention and management of bacterial disease in mandarin fish remains incomplete. Therefore, there is a need for more comprehensive insights into the preventive and curative strategies to address these bacterial infections. In this review, we summarize the information pertaining to the predominant bacterial pathogens such as Aeromonas spp., Flavobacterium columnare, Edwardsiella tarda, Streptococcus uberis and Vibrio cholerae in the mandarin fish aquaculture, and point out the current strategies for diagnosis and combating these bacterial pathogens, as well as deliberate on the prospective alternative treatments such as vaccines, herbal remedies, and phage therapy for the prevention and control of these bacterial diseases. Furthermore, we also highlights the importance to implement an integrated bacterial disease management (IBDM) approach for the prevention and control of these pathogenic bacteria in aquaculture.

9.
BMC Infect Dis ; 24(1): 1106, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39367344

RESUMEN

BACKGROUND: Scabies disproportionately affects people in resource-poor areas. Clinical diagnosis risks misdiagnosis due to resemblance to other skin diseases, but laboratory confirmation improves accuracy. Scabies allow for secondary bacterial infections. Associated bacteria exacerbate scabies and antibiotic resistance. Ethiopian scabies diagnosis relies solely on clinical exams without confirming parasites or investigating secondary bacterial infections. This study aims to identify parasites via scraping, isolate secondary bacteria, and evaluate their antibiotic susceptibility profiles. METHODS: A hospital based cross-sectional study was conducted from September 2022 to July 2023 among scabies suspected patients who visited the dermatology clinic at Borumeda General Hospital in Northeast Ethiopia. A systematic random sampling technique was used to select 422 study participants. Socio-demographic, hygiene, and clinical characteristics data were collected via face-to-face interviews and observation. Skin scrapings for parasitological investigations and swab samples for microbiological investigations were collected and transported for analysis and drug susceptibility testing. Descriptive statistics and logistic regression analysis were employed to assess risk factors. RESULT: Among 422 skin scraping samples, 156 (37.0%) cases of scabies were microscopically confirmed. Bed-sharing and having contact history were independent predictors of microscopically confirmed scabies. The prevalence of secondary bacterial infections among scabies-confirmed patients was 35.9% (56/156). The most prevalent bacterial species were Staphylococcus aureus, coagulase-negative staphylococci, and Streptococcus pyogenes. Tetracycline for Gram-positive bacteria and ampicillin for Gram-negative bacteria showed the highest rate of resistance. In both Gram-positive and Gram-negative strains, multidrug resistance was also observed. CONCLUSION: This study found that over one-third of skin scrapings tested positive for scabies. Additionally, more than one-third of scabies cases were complicated by secondary bacterial infections. Improved scabies diagnosis and consideration of secondary bacterial infections are important for better controlling this neglected tropical disease.


Asunto(s)
Escabiosis , Escabiosis/epidemiología , Humanos , Etiopía/epidemiología , Masculino , Femenino , Estudios Transversales , Adulto , Prevalencia , Adolescente , Adulto Joven , Persona de Mediana Edad , Niño , Hospitales Generales , Coinfección/epidemiología , Coinfección/microbiología , Coinfección/parasitología , Preescolar , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Factores de Riesgo , Anciano
10.
Rev Esp Quimioter ; 2024 Oct 16.
Artículo en Español | MEDLINE | ID: mdl-39405171

RESUMEN

OBJECTIVE: To analyze the diagnostic accuracy of the new MeMed® test to predict bacterial infection in adult patients seen in emergency departments (ED) with clinical suspicion of infection, as well as to compare its performance with other commonly used biomarkers (protein C reactive-PCR-, procalcitonin -PCT-). METHODS: A prospective, observational and analytical study was carried out on adult patients who were treated in an ED with the clinical diagnosis of an infectious process. Follow-up was carried out for 30 days. The diagnosis of bacterial infection (BI) was considered as the dependent variable. The predictive ability was analyzed with the area under the curve (AUC) of the receiver operating characteristic (COR) and the values of sensitivity (Se), specificity (Es), positive predictive value (PPV) and negative predictive value (NPV) of the PCR, PCT, leukocyte count and the LIAISON® MeMed® test. RESULTS: The study included 258 patients, 54 (15.6%) of whom died within 30 days of visiting the ED. The mean age was 68.28 (SD 19.53) years, 57.4% (148) were men. At 30 days, the group with the IB diagnosis had 137 patients, the viral infection group 68 cases and 17 in the indeterminate group. The AUC-COR achieved by MeMed® in the group that analyzes all patients was 0.920 (95% CI: 0.877-0.962) and the PCT was 0.811 (95% CI: 0.754-0.867). With a cut-off point (PC) > 65 points of the MeMed® test, achieves a Se: 79.2% and Es: 91.2% and with PC > 90 points a Se: 57% and Es: 95.9%. Applying the Youden index, the PC > 50 points achieves Se:84.1% and Es:88.2%. CONCLUSIONS: In adult patients treated with clinical suspicion of infection in the ED, the LIAISON MeMed® test has a great ability to diagnose its bacterial origin and achieves better performance than PCT, PCR and leukocyte count.

11.
Mol Imaging Biol ; 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39407054

RESUMEN

PURPOSE: Bacterial infection causes significant mortality and morbidity worldwide despite the availability of antibiotics. Differentiation between responders and non-responders early on during antibiotic treatment will be informative to patients and healthcare providers. Our objective was to investigate whether PET imaging with 18F-Fluorodeoxysorbitol (18F-FDS) or 18F-FDG can be used to differentiate responders from non-responders to antibiotic treatment. PROCEDURES: NTUH-K2044 was used for infection in Albino C57 female mice. Each mouse was inoculated intratracheally with NTUH-K2044 to induce lung infection (n = 8). For treatment studies, two bacterial doses for animal inoculation and two treatment starting times were compared to optimize treatment profiles. 18F-FDS or 8F-FDG /PET imaging was performed to monitor treatment progression. RESULTS: Our results demonstrated that the treatment profiles for mice infected with 25 CFU hvKp and antibiotic treatment starting at 24 p.i. were not ideal due to no evidence of lung infection and lack of treatment efficacy. The optimal scheme is to use 250 CUF for infection and start antibiotic treatment at 24 h p.i. to monitor antimicrobial efficacy. 75% of the mice were classified as responders to antibiotic treatment. 25% of the mice were classified as non-responders. 18F-FDG was used to compare with 18F-FDS, but all mice showed increased lung uptake of 18F-FDG during 3-day treatments. CONCLUSIONS: 18F-FDS is a promising PET tracer to image bacterial infection. It can be used to monitor response to treatment, and differentiate responders from non-responders to antibiotic treatment, but 18F-FDG cannot, probably due to the presence of high degree of inflammation before and after treatment.

12.
Cureus ; 16(9): e69194, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39398664

RESUMEN

Actinomycosis is a rare chronic infectious disease, most commonly affecting the cervicofacial, pulmonary, or genitourinary areas. It is caused by the Actinomyces spp. bacteria, which are facultative anaerobes and gram-positive, nonsporing rods. The disease is characterized by the formation of cold abscesses or fistulas, as well as granulomatous tissue, reactive fibrosis, and necrosis, which can resemble local malignancy. Cutaneous actinomycosis in the trunk or extremities is extremely rare and is usually related to previous surgical procedures or trauma. However, we report one such rare case of cutaneous actinomycosis of the forearm without previous precipitating factors, which was successfully treated with prolonged antibiotherapy.

13.
J Lipid Res ; : 100668, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39395788

RESUMEN

The recent advances in mass spectrometry (MS) technologies have enabled comprehensive lipid profiling in biological samples. However, the robustness and efficiency of MS-based lipidomics is compromised by the complexity of biological samples. High-field asymmetric waveform ion mobility spectrometry (FAIMS) is a technology that can continuously transmit one type of ion, independent of mass-to-charge ratio. Here we present the development and application of LC-FAIMS-MS/MS based platform for untargeted lipidomics. We used 3 optimally balanced compensation voltages, i.e., 29 V, 34 V and 39 V, to analyse all subclasses of glycerophospholipids. The reproducibility of the method was evaluated using reference standards. The reproducibility of retention times ranged from 0.9 to 1.5 % RSD; whereas RSD values of 5-10 % were observed for peak areas. More importantly, the coupling of a FAIMS device can significantly improve the robustness and efficiency. We exploited this NPLC-FAIMS-HRMS to analyze the serum lipid profiles in mice infected intranasally with Acinetobacter baumannii. The temporal profiles of serum lipids after A. baumannii inoculation were obtained for 4 h, 8 h and 24 h. We found that nearly all ether PC and ether PE lipids were significantly decreased 8 h after inoculation. The resultant volcano plot illustrated the distribution of 28 increased and 28 decreased lipid species in mouse sera 24 h after inoculation. We also found that a single ether PE composition can comprise multiple isomeric structures, and the relative abundance of each isomer could be quantified using the newly developed NPLC-FAIMS-PRM method.

14.
Cureus ; 16(9): e69460, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39411639

RESUMEN

Cutibacterium acnes, previously known as Propionibacterium acnes, is a gram-positive rod in the pilosebaceous glands and commonly implicated in acne vulgaris. Its role in prosthetic joint infections, particularly in shoulder surgeries, has recently gained attention due to its prevalence around the shoulder girdle. This review collates evidence on the pathogenic role of C. acnes in shoulder surgeries, discussing preventive measures, risk factors, clinical presentation, investigation, and treatment strategies. C. acnes infections are complex, often presenting with non-specific symptoms and delayed diagnoses. Risk factors include male sex, presence of hair, shoulder steroid injections, and previous shoulder surgeries. Investigations such as inflammatory markers, synovial fluid analysis, diagnostic arthroscopy, tissue cultures, and advanced molecular techniques like next-generation sequencing and multiplex polymerase chain reaction are explored for their effectiveness in detecting C. acnes. Treatment strategies range from prolonged antibiotics and antibiotic spacers to single-stage and two-stage revision surgeries. Studies indicate that single-stage revision may provide better outcomes compared to two-stage revision. Effective management of C. acnes infections requires careful assessment, relevant investigations, and tailored treatment approaches. This review emphasizes the need for further research to address intraoperative contamination and to develop more efficient diagnostic and treatment methods.

15.
Phage (New Rochelle) ; 5(3): 130-142, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39372361

RESUMEN

Poultry production faces challenges from bacterial infections, aggravated by antibiotic resistance, affecting bird welfare and the industry's economy. Bacteriophages show promise as a solution, but their use in poultry systems is still limited. This study uses scientometric analysis to investigate the incidence of bacterial infections in poultry systems and bacteriophage application trends. The Web of Science database was used, and the articles were refined by searching for keywords that included the most rep orted bacteria in the different phases of poultry farming and the application of phages. The articles were analyzed using the CiteSpace and Excel software, allowing the evaluation of publication trends, influential countries, and correlations with antimicrobial resistance and the use of bacteriophages. Results highlight Escherichia coli prevalence in poultry systems and reveal a correlation between the number of publications and poultry productivity, with the United States and China leading both aspects. Findings offer insights into bacterial control gaps in poultry systems, underscoring the need for further research and practical strategies.

17.
Autophagy ; : 1-17, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39291751

RESUMEN

The KEAP1-NFE2L2 axis is essential for the cellular response against metabolic and oxidative stress. KEAP1 is an adaptor protein of CUL3 (cullin 3) ubiquitin ligase that controls the cellular levels of NFE2L2, a critical transcription factor of several cytoprotective genes. Oxidative stress, defective autophagy and pathogenic infections activate NFE2L2 signaling through phosphorylation of the autophagy receptor protein SQSTM1, which competes with NFE2L2 for binding to KEAP1. Here we show that phosphoribosyl-linked serine ubiquitination of SQSTM1 catalyzed by SidE effectors of Legionella pneumophila controls NFE2L2 signaling and cell metabolism upon Legionella infection. Serine ubiquitination of SQSTM1 sterically blocks its binding to KEAP1, resulting in NFE2L2 ubiquitination and degradation. This reduces NFE2L2-dependent antioxidant synthesis in the early phase of infection. Levels of serine ubiquitinated SQSTM1 diminish in the later stage of infection allowing the expression of NFE2L2-target genes; causing a differential regulation of the host metabolome and proteome in a NFE2L2-dependent manner.Abbreviation: ARE: antioxidant response element; Dup: deubiquitinase specific for phosphoribosyl-linked serine ubiquitination; ER: endoplasmic reticulum; h.p.i: hours post infection; HIF1A/HIF-1α: hypoxia inducible factor 1 subunit alpha; KEAP1: kelch like ECH associated protein 1; KIR: KEAP1-interacting region; LIR: LC3-interacting region; NES: nuclear export signal; NFKB/NF-κB: nuclear factor kappa B; NLS: nuclear localization signal; NFE2L2/Nrf2: NFE2 like bZIP transcription factor 2; PB1 domain: Phox1 and Bem1 domain; PR-Ub: phosphoribosyl-linked serine ubiquitination; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; tBHQ: tertiary butylhydroquinone; TUBE2: tandem ubiquitiin binding entity 2; UBA domain: ubiquitin-associated domain.

18.
Artículo en Inglés | MEDLINE | ID: mdl-39332598

RESUMEN

BACKGROUND: There has been an unprecedented increase of immunocompromised (IC) patients in clinical practice due to various reasons. Bacterial infections are a major cause of morbidity and mortality in this population. Emerging antibacterial resistance poses a significant challenge for prophylaxis and treatment. OBJECTIVES: We aim to provide an update on antibacterial prophylaxis and management, particularly in high-risk IC patients, including those with acute leukaemia and haematopoietic stem cell transplantation. SOURCES: We reviewed original articles, systematic reviews, metanalyses and guidelines using PubMed, Scopus and Web of Science. CONTENT: We discussed the pros and cons of fluoroquinolone (FQ) prophylaxis in neutropenic patients in the context of personalized medicine. We also attempted to give an outline of empirical treatment of presumed bacterial infections and targeted therapy options for documented bacterial infections considering the recent surge of multiresistant bacteria in haematological cancer patients and local epidemiology. The shortcomings of the current strategies and future needs are discussed in detail. IMPLICATIONS: Antibacterial prophylaxis with FQs may still have a role in preventing bacterial infections in carefully selected high-risk haematology patients. Empirical treatment algorithms still need to be adjusted according to host and local factors. Use of rapid diagnostic methods may lessen the need of broad spectrum empirical antibiotic usage. However, these tests may not be easily available due to budget constraints in countries with limited resources but high rate of the bacterial resistance. Although new antimicrobials provide opportunities for effective and less toxic treatment of highly resistant bacterial infections, large-scale data from IC patients are very limited. Using data-driven approaches with AI tools may guide the selection of appropriate patients who would benefit most from such prophylactic and treatment regimens.

19.
Cureus ; 16(8): e67909, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39347175

RESUMEN

Leptospirosis is a bacterial infection caused by the pathogen Leptospira. The disease is primarily transmitted through contact with animals (mainly rats) or through exposure to contaminated water or soil. Underdeveloped countries and places with poor housing and sanitation are at higher risk. Leptospirosis often presents with nonspecific symptoms, making it difficult to diagnose. This can delay the initiation of appropriate treatment. In the case presented, the patient had a history of cough, high fever, and a rash over various parts of the body. This combination of respiratory symptoms, systemic fever, and dermatological manifestations led to the suspicion of an infection. Initial blood examinations revealed a significantly increased white blood cell (WBC) count, indicating an infection. Further enzyme-linked immunosorbent assay (ELISA) testing was confirmed by active immunoglobulin M (IgM) antibodies specific to leptospira species, followed by a chest X-ray scan. The antibiotics doxycycline (for seven days) and ceftriaxone (two weeks) were used to treat the leptospirosis. The patient was also given antipyretics to bring down fever and antitussive agents to suppress the cough. Hydration and breathing exercises were also given high priority in healing from this illness. After treatment, the patient did very well, he sweated less before dawn, the rash started to go away, and finally, even coughing was controlled. Further blood tests have shown that now the WBC is in the normal range and the IgM antibody level has dropped. In other words, the infection has been eradicated. For detailed information, refer to the case study "A Moral Call," which argues that early treatment and intervention are critical in managing leptospirosis. Getting this severe infection with early antibiotic therapy and nursing care gives people a chance for complete recovery from their illness. There must be more studies into this disease's long-term effects and how to prevent it when the risk group is more significant.

20.
Gene ; 933: 148969, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39341518

RESUMEN

Commensal bacteria that breach endothelial barrier has been reported to induce low grade chronic inflammation producing disease symptoms in major peripheral tissues. In this study, we investigated the role of genetically modified cellular invasive form of commensal E. coli K12 (SK3842) in cognitive impairment. Low-grade systemic infection model was developed using recurring peripheral inoculation of live bacteria in Wistar rats. To examine memory parameters, Novel object recognition test and Radial arm maze test were performed. Differential protein expression profiling of rat hippocampus was carried out using LC-MS/MS and subsequently quantified using SWATH. HBA1/2, NEFH, PFN1 and ATP5d were chosen for validation using quantitative RT-PCR. Results showed drastic decline in Recognition memory of the SK3842 infected rats. Reference and Working Memory of the infected group were also significantly reduced in comparison to control group. Proteome analysis using LC-MS/MS coupled with SWATH revealed differential expression of key proteins that are crucial for the maintenance of various neurological functions. Moreover, expression of NEFH and PFN1transcripts were found to be in line with the proteomics data. Protein interaction network of these validated proteins generated by STRING database converged to RhoA protein. Thus, the present study establishes an association between peripheral infection of a hippocampal protein network dysregulation and overall memory decline.

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