Future microbiology最新文献

Aim: Transplant rejection and failure are the primary causes of shortened lifespan in transplant patients and are closely associated with the status of the human immune system. Gut microbiota have the capacity to modulate the human immune system. However, it remains unclear whether any gut microbiota can influence the risk of transplant failure.Materials & methods: A Mendelian randomization study was conducted to explore the causal relationship between gut microbiota and transplant failure. This study utilized three Genome-Wide Association Study results focusing on the gut microbiome, transplant failure and transplantation status. Single nucleotide polymorphisms that were strongly associated with gut microbiota abundance were selected as instrumental variables.Results: The abundance of Bifidobacteriaceae demonstrated a significant causal relationship with transplant failure (inverse variance weighted [IVW] p = 0.049, OR = 0.658, 95% CI: 0.433-0.998), but was not related to the risk of transplantation status (IVW p > 0.200). Notably, a higher intestinal abundance of Bifidobacteriaceae corresponded to a decreased risk of transplant failure. Bifidobacteriaceae instrumental variables were enriched in pathways related to synapses and membranes.Conclusion: The Bifidobacteriaceae may play a crucial role in the mechanism of transplant failure. These study results contribute to elucidating the mechanisms underlying transplant failure.

Aim: This work aimed to test peptides against the planktonic and biofilm form of Cryptococcus spp. and in vitro toxicity using three-dimensional (3D) cells characterized and evaluate in vivo toxicity in Galleria mellonella.Materials & methods: Susceptibility tests were conducted on the planktonic form and biofilm formation. The toxicity of the peptides was evaluated in lung and brain cells in monolayer (2D) and 3D mono- and co-culture, in addition to in vivo analysis with G. mellonella.Results: Susceptibility values ranged from 31.25 to over 250 µg/ml with a fungicidal profile. Regarding toxicity, the PepM2 peptide was not toxic in 3D culture (500 µg/ml). G. mellonella, showed a survival rate of more than 85% In assays with brain and lung cell lines, concentrations ranged from 4 × 10⁴ to 4 × 10³ cells/well for brain cells and 1 × 10³ cells/well for lung cells. Cocultures used 1 × 10⁵ brain and 1 × 10³ lung cells.Conclusion: This study shows that the peptides have great potential against cryptococcosis, and all spheroids were characterized as having a spheroidal and compact structure.

Aim: Tuberculous meningitis (TBM) is one of the most severe clinical forms of tuberculosis (TB). Since epidemiological studies can contribute to TB control, we conducted a review and meta-analysis of epidemiological publications of adults TBM cases in countries with high incidence of TB.Materials & methods: The search resulted in 11,855 articles, in which 21 ultimately were included in our review and 15 in our meta-analysis.Results: TBM mortality was 25% with death rates of 70% in Africa. The review showed different and non-concordant diagnostic techniques and treatment schemes.Conclusion: Adults living in the African region are at high risk of death from TBM, highlighting an urgent need of guidelines to support diagnosis and treatment, and ultimately, to reduce mortality.

Metagenomic next-generation sequencing (mNGS) in diagnosis of human brucellosis is comparatively unexplored. This report details five human brucellosis cases diagnosed using mNGS based on Illumina sequencing platform, comprising three females and two males, four with epidemiological exposure. In cases 1 and 2, plasma mNGS results showed one positive and one negative for Brucella melitensis, and subsequent blood cultures were both positive. Cases 3, 4 and 5 involved spinal brucellosis, some with paravertebral abscesses. mNGS from infectious tissue samples successfully detected Brucella, with read counts ranging between 30 and 1314, yet cultures were negative in cases 4 and 5. Following antibiotic and surgical treatments, all patients showed clinical improvement. This report shows mNGS testing enhances the detection sensitivity of brucellosis diagnosis.

Aim: To evaluate the antifungal activity of mangiferin against Candida spp. resistant to fluconazole.Materials & methods: The antifungal activity of mangiferin was assessed using broth microdilution and its interaction with azoles and amphotericin B was evaluated by checkerboard. The activity of mangiferin against Candida spp. biofilms was assessed using the MTT colorimetric assay and its possible mechanism of action was evaluated using flow cytometry.Results: Mangiferin showed activity against Candida albicans, Candida tropicalis and Candida parapsilosis resistant to fluconazole and showed synergism with azoles and amphotericin B. Mangiferin increased the activity of antifungals against Candida biofilms and caused depolarization of the mitochondrial membrane and externalization of phosphatidylserine, suggesting apoptosis.Conclusion: mangiferin combined with antifungals has potential against Candida spp.

Aim: To compare the microbial communities inside hemodialysis catheters from symptomatic and asymptomatic patients to determine their differences.Materials & methods: Catheters (n = 41) were removed from patients in the Saskatchewan Health Authority over an 18-month period. The catheter section inside the body was flushed and the contents were evaluated using culture-dependent and culture-independent analysis.Results: All catheters were colonized by bacteria, with considerable overlap between groups based on microbial communities and the individual species detected. More Gram-negative species were detected by sequencing, whereas predominantly Gram-positive strains were cultured. Antibiotic resistance and biofilm formation was widespread and not correlated with either catheter group.Conclusion: Common pathogens were detected in each set of catheters, therefore predicting infections based on the microbiology is difficult.

Infectious diseases lead to significant morbidity and mortality. Often, resolution of the acute stage of the disease leads to microbial persistence, resulting in chronic debilitating disease. Management of persistent infections frequently requires lifelong therapy with antimicrobial agents. These infections could be chronic viral infections like HIV, hepatitis B or chronic bacterial persistent infections like prosthetic joint infections caused by multi-drug resistant organisms. Bacteriophages have been designed specifically to target recalcitrant bacterial infections, such as prosthetic joint infections with varying success. In this review, we describe the historic evolution of scenarios and risks associated with innovative therapy using infectious agents to treat other persistent infections.

Conventional itraconazole (c-ITZ) can be used for a variety of fungal infections although variable absorption has been a significant limitation. Super-bioavailable itraconazole (SUBA-ITZ) is a novel formulation that overcomes absorption concerns by utilizing a polymer-matrix to disperse active drug and facilitate dissolution. The pH-driven matrix allows concurrent proton pump inhibitor administration without significant effects on drug concentrations. The enhanced bioavailability of SUBA-ITZ allows for lower dosing, while achieving similar serum concentrations as c-ITZ and SUBA-ITZ is now US FDA approved in the treatment of blastomycosis, histoplasmosis and aspergillosis. Common side effects of SUBA-ITZ include gastrointestinal disorders, peripheral edema and drug-induced hypertension. Given the significant differences in pharmacokinetics between the formulations, c-ITZ and SUBA-ITZ capsules are not considered interchangeable. It is important to note that drug errors may occur when transitioning a patient from one formulation to another.

Aim: Understanding molecular mechanisms of Helicobacter pylori (H. pylori)-induced inflammation is important for developing new therapeutic strategies for gastrointestinal diseases.Materials & methods: We designed an H. pylori-neutrophil infection model and explored the effects of H. pylori infection on neutrophils.Results: H. pylori infected neutrophils showed a low level of apoptosis. H. pylori stimulation activated the NACHT/LRR/PYD domain-containing protein 3 (NLRP3)-gasdermin-D (GSDMD) pathway for interleukin (IL)-1β secretion. However, IL-1β secretion was not completely dependent on GSDMD, as inhibition of autophagy significantly reduced IL-1β release, and autophagy-related molecules were significantly upregulated in H. pylori-infected neutrophils.Conclusion: Therefore, H. pylori infection inhibits neutrophils apoptosis and induces IL-1β secretion through autophagy. These findings may be utilized to formulate therapeutic strategies against H. pylori mediated chronic gastritis.