Amoeba-inspired magnetic microgel assembly assisted by engineered dextran-binding protein for vaccination against lifethreatening systemic infection

Vaccination is critical for population protection from pathogenic infections.However,its efficiency is frequently compromised by a failure of antigen retention and presentation.Herein,we designed a dextran-binding protein DexBP,which is composed of the carbohydrate-binding domains of Trichoderma reesei cellobiohydrolases Cel6A and Cel7A,together with the sequence of the fluorescent protein mCherry.DexBP was further prepared by engineered Escherichia coli cells and grafted to magnetic nanoparticles.The magnetic nanoparticles were integrated with a dextran/poly(vinyl alcohol)framework and a reactive oxygen species-responsive linker,obtaining magnetic polymeric microgels for carrying pathogen antigen.Similar to amoeba aggregation,the microgels self-assembled to form aggregates and further induced dendritic cell aggregation.This step-by-step assembly retained antigens at lymph nodes,promoted antigen presentation,stimulated humoral immunity,and protected the mice from lifethreatening systemic infections.This study developed a magnetic microgel-assembling platform for dynamically regulating immune response during protection of the body from dangerous infections.

Pathogen infection-responsive nanoplatform targeting macrophage endoplasmic reticulum for treating life-threatening systemic infection

Systemic infections caused by life-threatening pathogens represent one of the main factors leading to clinical death.In this study,we developed a pathogen infection-responsive and macrophage endoplasmic reticulum-targeting nanoplatform to alleviate systemic infections.The nanoplatform is composed of large-pore mesoporous silica nanoparticles(MSNs)grafted by an endoplasmic reticulum-targeting peptide,and a pathogen infection-responsive cap containing the reactive oxygen speciescleavable boronobenzyl acid linker and bovine serum albumin.The capped MSNs exhibited the capacity to high-efficiently load the antimicrobial peptide melittin,and to rapidly release the cargo triggered by H_(2)O_(2) or the pathogen-macrophage interaction system,but had no obvious toxicity to macrophages.During the interaction with pathogenic Candida albicans cells and macrophages,the melittin-loading nanoplatform MSNE+MEL+TPB strongly inhibited pathogen growth,survived macrophages,and suppressed endoplasmic reticulum stress together with pro-inflammatory cytokine secretion.In a systemic infection model,the nanoplatform efficiently prevented kidney dysfunction,alleviated inflammatory symptoms,and protected the mice from death.This study developed a macrophage organelle-targeting nanoplatform for treatment of life-threatening systemic infections.

Phylogeny,ecology and taxonomy of systemic pathogens and their relatives in Ajellomycetaceae(Onygenales):Blastomyces,Emergomyces,Emmonsia,Emmonsiellopsis

The family Ajellomycetaceae(Onygenales)includes mammal-associated pathogens within the genera Blastomyces,Emmonsia,Histoplasma and Paracoccidioides,as well as the recently described genera,Emergomyces that causes disease in immunocompromised hosts,and Emmonsiellopsis,known only from soil.To further assess the phylogenetic relationships among and between members of these genera and several previously undescribed species,we sequenced and analyzed the DNA-directed RNA polymerase II(rPB2),translation elongation factor 3-a(TEF3),b-tubulin(TUB2),28S large subunit rDNA(LSU)and the internal transcribed spacer regions(ITS)in 68 strains,in addition to morphological and physiological investigations.To better understand the thermal dimorphism among these fungi,the dynamic process of transformation from mycelial to yeast-like or adiaspore-like forms was also assessed over a range of temperatures(6–42C).Molecular data resolved the relationships and recognized five major well-supported lineages that correspond largely to the genus level.Emmonsia,typified by Emmonsia parva,is a synonym of Blastomyces that also accommodates Blastomyces helicus(formerly Emmonsia helica).Emmonsia crescens is phylogenetically distinct,and found closely related to a single strain from soil without known etiology.Blastomyces silverae,Emergomyces canadensis,Emergomyces europaeus and Emmonsia sola are newly described.Almost all of the taxa are associated with human and animal disease.Emmonsia crescens,B.dermatitidis and B.parvus are prevalently associated with pulmonary disease in humans or animals.Blastomyces helicus,B.percursus,Emergomyces africanus,Es.canadensis,Es.europaeus,Es.orientalis and Es.pasteurianus(formerly Emmonsia pasteuriana)are predominantly found in human hosts with immune disorders;no animal hosts are known for these species except B.helicus.

Efficacy and safety of itraconazole use in infants

Background:Itraconazole has been used to treat fungal infections,in particular invasive fungal infections in infants or neonates in many countries.Data sources:Literature search was conducted through Ovid EMBASE,PubMed,ISI Web of Science,CNKI and Google scholarship using the following key words:“pediatric”or“infant”or“neonate”and“fungal infection”in combination with“itraconazole”.Based on the literature and our clinical experience,we outline the administration of itraconazole in infants in order to develop evidence-based pharmacotherapy.Results:Of 45 articles on the use of itraconazole in infancy,13 are related to superficial fungal infections including tinea capitis,sporotrichosis,mucosal fungal infections and opportunistic infections.The other 32 articles are related to systemic fungal infections including candidiasis,aspergillosis,histoplasmosis,zygomycosis,trichosporonosis and opportunistic infections as caused by Myceliophthora thermophila.Conclusion:Itraconazole is safe and effective at a dose of 5 mg/kg per day in a short duration of therapy for superficial fungal infections and 10 mg/kg per day for systemic fungal infections in infants.With a good compliance,it is cost-effective in treating infantile fungal infections.The profiles of adverse events induced by itraconazole in infants are similar to those in adults and children.