Biology subjects

Sarr, A.

Publications and source records attributed to Sarr, A..

3 recordsLinked to original sources

bioRxiv2025

AlphaFold-Multimer Modelling of Linked nAChR Subunits Challenges Concatemer Design Assumptions

Nicotinic acetylcholine receptors (nAChRs) are well described in vertebrates, yet less studied in arthropods, and the subunit stoichiometry of heteromeric arthropod nAChRs remains unresolved. This study combined a computational and experimental approach to predict and validate the stoichiometries of two heteromeric nAChRs from the parasitic arthropod Lepeophtheirus salmonis. AlphaFold2- and AlphaFold-Multimer-based modelling, supported by multiple sequence alignment and functional expression in Xenopus laevis oocytes, identified the most likely stoichiometries for two compositions of subunits previously described, named Lsa-nAChR1 and Lsa-nAChR2. For receptor Lsa-nAChR1, the highest scoring stoichiometry was 1b122b2. Lsa-nAChR2 exhibited three possible stoichiometries, confirmed by both computational modelling and experiments. These are 3{beta}23{beta}1{beta}2, 3{beta}13{beta}1{beta}2, and 333{beta}1{beta}2. All stoichiometries are written from a counterclockwise, extracellular orientation. Strikingly, structural modelling also suggested that linker flexibility in concatemer constructs may allow a novel conformation with a different subunit between the linked subunits, referred to here as "wedging". These results indicate that the use of flexible linker sequences does not reliably enforce subunit position or assembly directionality, as shown here for nAChRs. These findings challenge the assumption that linked concatemers unambiguously dictate receptor stoichiometry. Thus, interpretations of concatemer-based studies, on nAChRs and other receptor systems, may warrant careful reevaluation.

bioinformatics↗

bioRxiv2021

Borrelia infection in rodent host has dramatic effects on the microbiome of ticks

BackgroundVector-borne diseases remain major causes of human morbidity and mortality. It is increasingly recognized that the community of microbes inhabiting arthropods can strongly affect their vector competence, but the role of the tick microbiome in Borrelia transmission - the cause of Lyme disease - remains unclear. ResultsHere, we use a large-scale experiment to clarify the reciprocal interactions between Borrelia afzelii and the microbiome of Ixodes ricinus, its primary vector. In contrast to other reports, we find that depletion of the bacterial microbiome in larval ticks has no effect on their subsequent acquisition of B. afzelii during blood feeding on infected mice. Rather, exposure to B. afzelii-infected hosts drives pervasive changes to the tick microbiome, decreasing overall bacterial abundance, shifting bacterial community composition, and increasing bacterial diversity. These effects appear to be independent of the acquisition of B. afzelii by ticks, suggesting they are mediated by physiological or immunological aspects of B. afzelii infection in the rodent host. ConclusionsManipulation of the microbiome of I. ricinus larvae had no effect on their ability to acquire B. afzelii. In contrast, B. afzelii infection in the mouse had dramatic effects on the composition of the gut microbiome in I. ricinus nymphs. Our study demonstrates that vector-borne infections in the vertebrate host shape the microbiome of the arthropod vector.

microbiology↗

bioRxiv2019

Maternal antibodies provide strain-specific protection against infection with the Lyme disease pathogen in a wild rodent

The vertebrate immune system can produce antibodies that protect the host against pathogens. Females can transmit antibodies to their offspring, which provide short-term protection against infection. The tick-borne bacterium Borrelia afzelii causes Lyme disease in Europe and consists of multiple strains that cycle between the tick vector (Ixodes ricinus) and vertebrate hosts such as the bank vole (Myodes glareolus). We used a controlled experiment to show that infected female bank voles transmit protective antibodies to their offspring that are specific for the strain of B. afzelii. To test the specificity of protection, the offspring were challenged with either the same strain to which the mothers had been exposed or a different strain. The maternal antibodies protected the offspring against the same strain, but not against the different strain. The offspring from the uninfected control mothers were equally susceptible to both strains. Our study shows that maternal antibodies provide strong but highly strain-specific protection against B. afzelii in an important rodent reservoir host. The transmission of maternal antibodies may have important consequences for the epidemiology of multiple-strain pathogens in nature.\n\nAuthor SummaryMany pathogens that cause infectious disease consist of multiple strains. In vertebrate hosts, the immune system can generate antibodies that are highly specific for different pathogen strains. Mothers can transmit these antibodies to their offspring and thereby protect them from infectious disease. To date, few studies have investigated whether this transgenerational transfer of protective antibodies is important for pathogens that cycle in wild animal populations. The tick-borne spirochete bacterium Borrelia afzelii causes Lyme disease in Europe and cycles between Ixodes ticks and wild rodent hosts, such as the bank vole (Myodes glareolus). The purpose of our study was to test whether female bank voles infected with B. afzelii transmit antibodies to their offspring that protect them from an infected tick bite. Our study found that infected mothers do transmit antibodies, but the offspring were only protected against the strain of B. afzelii to which their mothers had been exposed and not to a different strain (i.e. protection was highly strain-specific). The broader implications of our study is that the transfer of protective antibodies between generations in the vertebrate host population could be important for organizing the community of pathogen strains that circulate in nature.

immunology↗