bioRxiv Science⌕ Search

Biology subjects

Winterford, C.

Publications and source records attributed to Winterford, C..

2 recordsLinked to original sources

Wolbachia wAlbB inhibit dengue and Zika infection in the mosquito Aedes aegypti with an Australian background

Biological control of mosquito vectors using the insect-specific bacteria Wolbachia is an emerging strategy for the management of human arboviral diseases. We recently described the development of a strain of Ae. aegypti infected with the Wolbachia strain wAlbB (referred to as the wAlbB2-F4 strain) through simple backcrossing of wild type Australian mosquitoes with a wAlbB infected Ae. aegypti strain from the USA. Field releases of male wAlbB2-F4 mosquitoes resulted in the successful suppression of a wild population of mosquitoes in the trial sites by exploiting the strains Wolbachia-induced cytoplasmic incompatibility. We now demonstrate that the strain is resistant to infection by dengue and Zika viruses and is genetically similar to endemic Queensland populations. There was a fourfold reduction in the proportion of wAlbB2-F4 mosquitoes that became infected following a blood meal containing dengue 2 virus (16.7%) compared to wild type mosquitoes (69.2%) and a 6-7 fold reduction in the proportion of wAlbB2-F4 mosquitoes producing virus in saliva following a blood meal containing an epidemic strain of Zika virus (8.7% in comparison to 58.3% in wild type mosquitoes). Restriction-site Associated DNA (RAD) sequencing revealed that wAlbB2-F4 mosquitoes have > 98% Australian ancestry, confirming the successful introduction of the wAlbB2 infection into the Australian genomic background through backcrossing. Genotypic and phenotypic analyses showed the wAlbB2-F4 strain retains the insecticide susceptibility phenotype and genotype of the Australian mosquitoes. We demonstrate that the Wolbachia wAlbB2-F4, in addition to being suitable for suppression programs, can be effective in population replacement programs given its high inhibition of virus infection in mosquitoes. The ease at which a target mosquito population can be transfected with wAlbB2, while retaining genotypes and phenotypes of the target population, shows the robustness of this strain as a biocontrol agent against the Ae. aegypti mosquito itself as well as the pathogens it transmits. IMPORTANCEEpidemics of arthopod-borne virus (arbovirus) diseases affect millions of people and are becoming more frequent and widespread. A successful strategy to control these diseases is by infecting mosquito populations with benign, insect-specific Wolbachia bacteria that render mosquitoes refractory to infection with pathogenic arboviruses. Here we show that a strain of the major mosquito vector Ae. aegypti that was infected with Wolbachia following a simple back-cross mating procedure is refractory to infection with dengue and Zika viruses. Importantly, the genetic background of the strain is equivalent to the target population, which is important for persistence of the strain and regulatory approval.

microbiology↗

Serum glycoprotein biomarker validation for esophageal adenocarcinoma and application to Barrett’s surveillance

BACKGROUND & AIMSEsophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barretts esophagus (BE) with a low annual rate of conversion. Current endoscopy surveillance for BE patients is probably not cost-effective. Previously, we discovered serum glycoprotein biomarker candidates which could discriminate BE patients from EAC. Here, we aimed to validate candidate serum glycoprotein biomarkers in independent cohorts, and to develop a biomarker panel for BE surveillance.\n\nMETHODSSerum glycoprotein biomarker candidates were measured in 301 serum samples collected from Australia (4 states) and USA (1 clinic) using lectin magnetic bead array (LeMBA) coupled multiple reaction monitoring mass spectrometry (MRM-MS). The area under receiver operating characteristic curve was calculated as a measure of discrimination, and multivariate recursive partitioning was used to formulate a multi-marker panel for BE surveillance.\n\nRESULTSDifferent glycoforms of complement C9 (C9), gelsolin (GSN), serum paraoxonase/arylesterase 1 (PON1) and serum paraoxonase/lactonase 3 (PON3) were validated as diagnostic glycoprotein biomarker candidates for EAC across both cohorts. A panel of 10 serum glycoproteins accurately discriminated BE patients not requiring intervention [BE+/-low grade dysplasia] from those requiring intervention [BE with high grade dysplasia (BE-HGD) or EAC]. Tissue expression of C9 was found to be induced in BE, dysplastic BE and EAC. In longitudinal samples from subjects that have progressed towards EAC, levels of serum C9 glycoforms were increased with disease progression.\n\nCONCLUSIONSFurther prospective clinical validation of the confirmed biomarker candidates in a large cohort is warranted. A first-line BE surveillance blood test may be developed based on these findings.\n\nAbbreviations

biochemistry↗