Biology subjects

Vos, A.

Publications and source records attributed to Vos, A..

3 recordsLinked to original sources

bioRxiv2026

Menaquinone depletion resensitises bedaquiline-resistant tuberculosis

Tuberculosis remains a leading cause of global mortality, and rising bedaquiline resistance threatens the effectiveness of current drug-resistant treatment regimens. Bedaquiline resistance typically arises through mutations in Rv0678 that upregulate drug efflux and confer cross-resistance to multiple drug classes. Here, we identify and optimise a chemical series targeting MenG, a central enzyme in the menaquinone biosynthesis pathway, yielding potent bactericidal inhibitors with in vivo efficacy. Strikingly, MenG inhibition restored bedaquiline susceptibility in efflux-mediated resistant strains, an effect confirmed in vivo where combination therapy achieved a 99.8% reduction in bacterial burden compared with bedaquiline alone. Potentiation also extended to pretomanid and other key agents. Disruption of upstream menaquinone and shikimate pathway enzymes produced similar resensitisation, establishing these pathways as tractable targets for restoring drug susceptibility in Mycobacterium tuberculosis. These findings provide a novel strategy to overcome bedaquiline resistance and strengthen future regimens for efflux-mediated drug-resistant tuberculosis.

microbiology↗

bioRxiv2022

Oral rabies vaccination of dogs - experiences from a field trial in Namibia

Dog-mediated rabies is responsible for tens of thousands of human deaths annually, and in resource-constrained settings, vaccinating dogs to control the disease at source remains challenging. Currently, rabies elimination efforts rely on mass dog vaccination by the parenteral route. To increase the herd immunity, free-roaming and stray dogs need to be specifically addressed in the vaccination campaigns, with oral rabies vaccination (ORV) of dogs being a possible solution. Using a third-generation vaccine and a standardized egg-flavoured bait, bait uptake and vaccination was assessed under field conditions in Namibia. During this trial, both veterinary staff as well as dog owners expressed their appreciation to this approach of vaccination. Of 1,115 dogs offered a bait, 90% (n=1,006, 95%CI:91-94) consumed the bait and 72.9% (n=813, 95%CI:70.2-75.4) of dogs were assessed as being vaccinated, while for (11.7%, n=130, 95%CI:9.9-17.7) the status was recorded as "unkown" and 15.4% (n=172, 95%CI: 13.4-17.7) were considered as being not vaccinated. Smaller dogs and dogs offered a bait with multiple other dogs had significantly higher vaccination rates, while other factors, e.g. sex, confinement status and time had no influence. The favorable results of this first large-scale field trial further support the strategic integration of ORV into dog rabies control programmes. Given the acceptance of the egg-flavored bait under various settings worldwide, ORV of dogs could become a game-changer in countries, where control strategies using parenteral vaccination alone failed to reach sufficient vaccination coverage in the dog population.

microbiology↗

bioRxiv2019

Effects of mid-frontal brain stimulation on sustained attention

Sustained attention is defined as the ability to maintain attention over longer periods of time, which typically declines with time on task (i.e., the vigilance decrement). Previous studies have suggested an important role for the dorsomedial prefrontal cortex (mPFC) in sustained attention. In two experiments, we aimed to enhance sustained attention by applying transcranial electrical current stimulation over the mPFC during a sustained attention task. In the first experiment, we applied transcranial direct current stimulation (tDCS) in a between-subject design (n=97): participants received either anodal, cathodal, or sham stimulation. Contrary to our prediction, we found no effect of stimulation on the vigilance decrement. In the second experiment, participants received theta and alpha transcranial alternating current stimulation (tACS) in two separate sessions (n=47, within-subject design). Here, we found a frequency-dependent effect on the vigilance decrement, such that contrary to our expectation, participants performance over time became worse after theta compared to alpha stimulation. However, this result needs to be interpreted with caution given that this effect could be driven by differential side effects between the two stimulation frequencies. To conclude, across two studies, we were not able to reduce the vigilant decrement using tDCS or theta tACS.

neuroscience↗