The translational challenge in Chagas disease drug development

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. There is an urgent need for safe, effective, and accessible new treatments since the currently approved drugs have serious limitations. Drug development for Chagas disease has historically been hampered by the complexity of the disease, critical knowledge gaps, and lack of coordinated R&D efforts. This review covers some of the translational challenges associated with the progression of new chemical entities from preclinical to clinical phases of development, and discusses how recent technological advances might allow the research community to answer key questions relevant to the disease and to overcome hurdles in R&D for Chagas disease.

Functions of bacterial Toxin-Antitoxin systems / 生物工程学报

TA (Toxin-Antitoxin) systems are widely spread in chromosomes and plasmids of bacteria and archaea. These systems consist of two co-expression genes, encoding stable toxin and sensitive antitoxin, respectively. The toxicity of toxins usually inhibits bacterial growth and antitoxins can neutralize the toxins. Interaction between them would regulate the growth state of bacteria precisely. According to the composition of TA and nature of antitoxin, six types of TA have been found. The role of these TA systems in bacteria has been a hot research topic in recent years. Now, the research status on functions of bacterial TA is reviewed.

Relationship and conversion between persisters and antimicrobial resistant bacteria / 中华微生物学和免疫学杂志

Persisters are a sub-population of bacteria that can survive lethal concentrations of antibiotics.They contribute to recurrent or intractable chronic infections.Persisters can emerge as a result of multiple mechanisms which lead to drug tolerance.Unlike antimicrobial resistance which usually acquires genetic mutation, phenotypes of persisters are non-inheritable.Despite the distinct difference between persistence and resistance, recent studies have demonstrated that not only persistence can be observed in resistant mutants, but also persisters themselves can be regarded as an intermediate state which promotes the emergence of resistance.This review focuses on mechanisms of drug tolerance in persisters, phenomena of persistence in antimicrobial resistant bacteria and possible mechanisms of the conversion of persisters to resistant bacteria.Moreover, future research directions are also prospected is this review.

Research of the effect of persisters in Candida albicans biofilm on antifungal therapy using a Caenorhabditis elegans infection model / 中华微生物学和免疫学杂志

Objective To illuminate the effect of persisters on antifungal therapy by infecting Caenorhabditis elegans as a live-animal model with Candida albicans isolates of different persister levels, treating them with amphotericin B and comparing the survival rate. Methods Glp-4 (bn2ts); sek-1 (km4) worms were synchronized and grown to sterile to L4-stage, put on different Candida albicans strains lawns separately for 2 h. Dispensed 15-20 worms per well of the 96-well plate, and added serial dilutions of amphotericin B for each strain group. Wells filled without any amphotericin B were used as negative controls intra-group. Incubated the plate at 25C for 5 days, counted the survival rate of each well. Results Compared with negative controls, survival rate of drug wells in each group increased. In the same drug concentration, the increase for high-persister group was significantly lower than that for low-persister group (P＜0.01). Conclusion Caenorhabditis elegans provides a model for the study of persisters and antifungal pharmacodynamics.The drug tolerance of persisters may be a critical component responsible for antifungal drug failure and relapsing infections.