Electrochemical Strategy for Eradicating Fluconazole-Tolerant Candida albicans Using Implantable Titanium.

A persistent problem in modern health care derives from the overwhelming presence of antibiotic-resistant microbes on biomaterials, more specifically, fungal growth on metal-based implants. This study seeks to investigate the antifungal properties of low-level electrochemical treatments delivered using titanium electrodes against Candida albicans. We show that C. albicans can be readily controlled with electrical currents/potentials, reducing the number of viable planktonic cells by 99.7% and biofilm cells by 96.0-99.99%. Additionally, this study explores the ability of the electrochemical treatments to potentiate fluconazole, a clinically used antifungal drug. We have found that electrochemical treatment substantially enhances fluconazole killing activity. While fluconazole alone exhibits a low efficiency against the stationary phase and biofilm cells of C. albicans, complete eradication corresponding to 7-log killing is achieved when the antifungal drug is provided subsequently to the electrochemical treatment. Further mechanistic analyses have revealed that the sequential treatment shows a complex multimodal action, including the disruption of cell wall integrity and permeability, impaired metabolic functions, and enhanced susceptibility to fluconazole, while altering the biofilm structure. Altogether, we have developed and optimized a new therapeutic strategy to sensitize and facilitate the eradication of fluconazole-tolerant microbes from implantable materials. This work is expected to help advance the use of electrochemical approaches in the treatment of infections caused by C. albicans in both nosocomial and clinical cases.

Blood meal-induced inhibition of vector-borne disease by transgenic microbiota.

Vector-borne diseases are a substantial portion of the global disease burden; one of the deadliest of these is malaria. Vector control strategies have been hindered by mosquito and pathogen resistances, and population alteration approaches using transgenic mosquitos still have many hurdles to overcome before they can be implemented in the field. Here we report a paratransgenic control strategy in which the microbiota of Anopheles stephensi was engineered to produce an antiplasmodial effector causing the mosquito to become refractory to Plasmodium berghei. The midgut symbiont Asaia was used to conditionally express the antiplasmodial protein scorpine only when a blood meal was present. These blood meal inducible Asaia strains significantly inhibit pathogen infection, and display improved fitness compared to strains that constitutively express the antiplasmodial effector. This strategy may allow the antiplasmodial bacterial strains to survive and be transmitted through mosquito populations, creating an easily implemented and enduring vector control strategy.

Draft Genome Sequence of Asaia sp. Strain SF2.1, an Important Member of the Microbiome of Anopheles Mosquitoes.

Asaia spp. are abundant members of the microbiota of Anopheles mosquitoes, the principle vectors of malaria. Here, we report the draft genome sequence of Asaia sp. strain SF2.1. This strain is under development as a platform to deliver antimalarial peptides and proteins to adult female Anopheles mosquitoes.