Biology subjects

Tachedjian, G.

Publications and source records attributed to Tachedjian, G..

4 recordsLinked to original sources

bioRxiv2026

Characterisation of vaginal Lactobacillus isolates from South African women towards the development of a biotherapeutic to optimise the vaginal microbiome

HIV remains among the worlds most serious healthcare challenges, with adolescent girls and young women in sub-Saharan Africa at particularly high risk of infection. Bacterial vaginosis (BV) is a key risk factor for HIV acquisition, however current treatment strategies are limited. Optimal vaginal Lactobacillus spp. protect against BV and HIV, largely through immunoregulatory and antimicrobial activities mediated in part by lactic acid. Towards the development of a Lactobacillus-containing live biotherapeutic for African women, we sampled 181 vaginal Lactobacillus isolates from 25 BV-negative South African women. Fifty isolates were selected for evaluation of inflammatory responses using vaginal epithelial cells, D- and L-lactate and lactic acid production and culture acidification. Aside from a single Lactobacillus salivarius strain, L. crispatus isolates acidified the culture media the most and produced the most D- and L-lactic acid. Inflammatory cytokine responses to Lactobacillus strains were variable, with L. crispatus eliciting the lowest levels of cytokine production. When all properties were evaluated collectively, L. crispatus strains exhibited the most desirable biotherapeutic characteristics. Whole genome sequence analysis of ten L. crispatus isolates showed that the majority were more closely related to one another than to isolates from other geographical regions. This supports the need for live biotherapeutics to be tailored for the population of intended use. No antimicrobial resistance elements were detected, while putative bacteriocins and intact prophage sequences were identified in all isolates. L. crispatus isolates displayed characteristics essential for optimal live biotherapeutic performance, however additional analysis is required to determine the functionality of identified putative prophages. ImportanceHIV is a leading cause of morbidity and mortality in sub-Saharan Africa, where adolescent girls and young women are three times more likely to acquire HIV than their male counterparts. A key risk factor for HIV is bacterial vaginosis (BV), a condition characterised by the loss of beneficial Lactobacillus species and increased abundance of non-optimal, inflammatory bacteria. Although BV affects approximately 25% of women in sub-Saharan Africa, effective therapeutics are lacking. Live biotherapeutics containing optimal Lactobacillus spp. represent a promising strategy to improve BV treatment outcomes and reduce HIV infection risk. We isolated 181 vaginal Lactobacillus spp. from 25 BV-negative South African women and characterized 50 selected isolates. This led to the identification of live biotherapeutic candidates for African women with distinct genomes compared to isolates from other geographical regions. This study contributes to current knowledge of the characteristics that should be considered when screening novel isolates for this purpose.

microbiology↗

bioRxiv2025

APOBEC5: characterisation of a novel member of the AID/APOBEC protein family

The AID/APOBEC protein family is involved in diverse biological processes, most notably antiviral innate immunity, a function carried out by APOBEC3 (A3) in placental mammals. A3 is exclusive to this lineage, having emerged after the divergence from marsupials. This raises the question of how marsupials, which lack A3, defend against retroviruses. An uncharacterized A3 homologue, APOBEC5 (A5), is present in marsupial genomes and in some other vertebrate taxa. Here, we use in silico and in vitro approaches to investigate whether A5 serves as a functional antiviral counterpart to A3 in marsupials and whether marsupial genomes contain evidence of past A3-like activity against retroviral infections. We find that A5 was present in the last common ancestor of all jawed vertebrates but has been lost independently in multiple lineages. A5 exhibits unique structural and post-translational features not observed in APOBEC3 or other APOBEC proteins and has a broad subcellular and tissue distribution, suggesting a multifunctional role. Mutagenesis assays demonstrate that A5 functions as a DNA mutator and modestly restricts the infectivity of a model retrovirus, HIV-1, and that this activity is counteracted by the HIV-1 protein, Vif. Furthermore, analysis of the gray short-tailed opossum genome reveals distinct patterns of A3-like restriction in two groups of recently integrated retroviruses, providing direct evidence of an ongoing evolutionary conflict between marsupial APOBEC proteins and retroviruses. This study presents the first characterisation of A5 as a novel AID/APOBEC family member and reveals that marsupials possess an antiviral function homologous to placental A3, shedding light on the evolutionary dynamics of vertebrate antiviral immunity.

evolutionary biology↗

bioRxiv2024

KoRV-related retroviruses in diverse Australian and African rodent species

The koala retrovirus (KoRV) is a key contributor to the ongoing decline of Australias koala population. KoRV has only been found in koalas and its enigmatic origins, as well as that of its close relative, the gibbon ape leukemia virus (GALV), have been a source of enduring debate. Bats and rodents are each proposed as major reservoirs of interspecies transmission with ongoing efforts to identify additional animal hosts of KoRV-related retroviruses. In this study we identified nine rodent species as novel hosts of KoRV-related retroviruses. Included among these hosts are two African rodents, revealing the first appearance of this clade beyond the Australian and Southeast Asian region. One of these African rodents, Mastomys natalensis, carries an endogenous KoRV-related retrovirus that is fully intact and potentially still infectious. Our findings suggest that rodents are the major carriers of KoRV-related retroviruses, with a potential point of origin in Southeast Asia.

microbiology↗

bioRxiv2020

Bats Possess Unique Variants of the Antiviral Restriction Factor Tetherin

Bats are recognised as important reservoirs of viruses deadly to other mammals, including humans. These infections are typically non-pathogenic in bats raising questions about host response differences that might exist between bats and other mammals. Tetherin is a restriction factor which inhibits the release of a diverse range of viruses from host cells, including retroviruses, coronaviruses, filoviruses, and paramyxoviruses, some of which are deadly to humans and transmitted by bats. Here we characterise the tetherin genes from 27 species of bats, revealing that they have evolved under strong selective pressure, and that fruit bats and vesper bats express unique structural variants of the tetherin protein. Tetherin was widely and variably expressed across fruit bat tissue-types and upregulated in spleen tissue when stimulated with Toll-like receptor agonists. The expression of two computationally predicted splice isoforms of fruit bat tetherin was verified. We identified an additional third unique splice isoform which includes a C-terminal region that is not homologous to known mammalian tetherin variants but was functionally capable of restricting the release of filoviral virus-like particles. We also report that vesper bats possess and express at least five tetherin genes, including structural variants, a greater number than any other mammal reported to date. These findings support the hypothesis of differential antiviral gene evolution in bats relative to other mammals.

evolutionary biology↗