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Dietrich, M.

Publications and source records attributed to Dietrich, M..

13 recordsLinked to original sources

Brown and Lesser noddies as epidemiological reservoirs and sentinels of avian influenza virus in the South-western Indian Ocean

Avian influenza virus (AIV) epidemiology is well-documented in temperate regions but remains poorly understood in isolated ecosystems like tropical oceanic islands. On these islands, seabirds nest in dense interspecific colonies where the role of different species as reservoirs and dispersers of AIV may vary greatly. Here, we examine the role of noddies (Anous spp.) as potential reservoirs for low pathogenic AIV and evaluate their potential as sentinel species for highly pathogenic AIV introduction on tropical oceanic islands. We analyzed blood samples from 11 seabird species across eight islands in the southwestern Indian Ocean (2015-2020). Noddies exhibited high, stable seroprevalence (30-45%), comparable to reservoir host species in temperate regions. The detection of two N7-positive noddies, sampled the same year on two distinct islands, provided direct molecular evidence that AIV actively circulates on these island colonies. While most other species showed low exposure, Bridled Terns (Onychoprion anaethetus) had exceptionally high seroprevalence (80%), though their reservoir status requires further investigation due to limited sampling. Given noddies consistent exposure and regional distribution, we recommend prioritizing islands with large noddy populations for AIV surveillance. Continued investigation of viral dynamics within and among islands is now called for to elucidate the ecological drivers of AIV maintenance and transmission.

ecology↗

How do urban-dwelling bats cope with urbanisation? Sex-dependent plasticity of stress, microbiome and pathogen shedding

Understanding wildlifes stress and infection response patterns is crucial, especially for species like bats that are ecologically important and potential zoonotic reservoirs. While highly sensitive to habitat destruction and land use change, bats have shown adaptability in human-modified landscapes. This study investigates the impact of urbanisation on the endemic Reunion free-tailed bat (Mormopterus francoismoutoui), which roosts in a variety of rapidly urbanised habitats. We analysed 412 urine samples from 11 roosts across Reunion Island, covering a gradient of urban and agricultural land use. We measured urinary cortisol, microbiome diversity and the shedding of Leptospira bacteria and paramyxovirus. After accounting for natural cortisol level variations due to circadian rhythm, age, sex, reproduction and capture-induced stress, we found that bats roosting in agricultural and urban areas were in better condition and had lower cortisol levels, suggesting adaptation to human-modified landscapes. Less-stressed bats had more diverse urinary microbiomes and reduced pathogen shedding, suggesting that landscape modifications may indirectly alter the natural epidemiology of bat-borne infectious agents. These patterns were particularly pronounced in females, supporting sex-dependent plasticity to urbanisation in bats. Our study highlights how rapid urbanisation may elicit plastic responses in bats, with potential cascading effects on zoonotic risk of transmission.

ecology↗

Urban bats change the menu: dietary plasticity across human-modified landscapes of a tropical island

In a rapidly urbanizing world, research on dietary habits of wildlife is essential to understand how plastic behaviors may guide evolutionary trajectories of endangered animal species. Bats are very sensitive to habitat destruction and land-use change, although some species have shown the capacity for adaptation to urban life. In this study, we tested to what extent urban insectivorous bats modify their feeding strategies in a recently human-modified tropical insular ecosystem. Using a DNA metabarcoding approach on fecal samples collected in seven roosts, we analyzed the dietary niche of free-tailed bats (Mormopterus francoismoutoui) endemic to Reunion Island. Our results revealed a wide dietary niche, including 174 arthropod species in 12 orders, among which lepidopterans were predominant. We identified several crop pests and disease vectors, highlighting the central role of this bat species for agroecology and epidemiology concerns. Our study also highlighted potential sex- and reproduction-related dietary strategies. Moreover, we found that agriculture areas, inferred from land cover surrounding bat roosts, were associated with higher relative abundance of Lepidoptera in the diet of bats. In contrast, bats roosting in urban areas increased their consumption of Blattodea. As Reunion free-tailed bats roost and thrive in human-modified landscapes, understanding the consequences of this dietary plasticity for bat health and fitness will be necessary for urban evolutionary research and conservation actions.

ecology↗

Pfs48/45 nanobodies block Plasmodium falciparum transmission

Malaria parasite fertilisation occurs within the Anopheles mosquito midgut. Interventions that inhibit parasite fertilisation prevent ongoing transmission and are important for malaria elimination efforts. Pfs48/45 and Pfs230 are two leading transmission-blocking vaccine candidates. Both proteins form a complex on the surface of sexual stage parasites and are essential for male fertility. Here we have identified nanobodies against Pfs48/45 that recognise gametocytes and have strong transmission-reducing activity. The crystal structure of our most potent nanobody in complex with Pfs48/45 reveals it binds a distinct epitope to TB31F, a leading transmission-blocking monoclonal antibody. In addition, we generated bispecific nanobodies that can target both Pfs48/45 and Pfs230 simultaneously and are fused to a human Fc domain. Our results show that these bispecific nanobodies recognise both Pfs48/45 and Pfs230 and reduce malaria parasite fertilisation in Anopheles stephensi. These results demonstrate the potential of nanobodies as a versatile antibody format that can reduce malaria transmission. Author SummaryMalaria is spread when an infected Anopheles mosquito bites a human. Within the female Anopheles mosquito, malaria parasite fertilisation occurs in the mosquito midgut. If you inhibit parasite fertilisation in the mosquito, you can prevent onward transmission of the malaria parasite from mosquito to humans. Transmission blocking vaccines work by stopping parasite fertilisation and development in the mosquito and are key for malaria elimination by preventing community spread. Pfs48/45 and Pfs230 are two leading transmission-blocking vaccine candidates, and both are critical for male fertility. Here we describe the generation of nanobodies that target Pfs48/45. We show that when nanobodies against Pfs48/45 were added to infected blood meals for Anopheles mosquitoes, the nanobodies significantly reduced parasite transmission. In addition, we generated bispecific nanobodies that target both Pfs48/45 and Pfs230 and these bispecific nanobodies also significantly reduced oocyst development. Our work demonstrates the potential of nanobodies as a versatile antibody format that can reduce malaria transmission.

microbiology↗

Cryo-EM structure of endogenous Plasmodium falciparum Pfs230 and Pfs48/45 fertilization complex

Plasmodium falciparum Pfs230 and Pfs48/45, part of a core fertilization complex, are leading malaria transmission-blocking vaccine candidates. However, how the two proteins interact is unknown. Here we report a 3.36 [A] resolution cryo-electron microscopy structure of the endogenous Pfs230-Pfs48/45 complex. We show that Pfs48/45 interacts with Pfs230 domains 13 and 14, domains that are not included in current Pfs230 vaccine immunogens. Using a transgenic parasite line with a domain 13 to 14 deletion, we show that these domains are essential for Pfs230 localization on the gamete surface. Furthermore, this line significantly reduced oocyst formation in the mosquito midgut, showing that the presence of Pfs230 domains 13 and 14 is critical for successful fertilization. Nanobodies against domains 13 and 14 inhibit Pfs230-Pfs48/45 complex formation, reduce transmission and structural analyses reveal their binding epitopes. Furthermore, domains 13 and 14 are targets of naturally acquired immunity and when delivered as mRNA-LNP immunizations induce potent immune responses and blocked transmission of malaria parasites. Our comprehensive structural insights on a core P. falciparum fertilization complex will guide the design of novel transmission-blocking vaccine candidates against malaria.

microbiology↗

Bat things come in threes: within-host dynamics of herpesvirus triple infection in bats

Understanding viral community ecology in bats is essential for elucidating shedding patterns and the drivers of co-infections. In this study, we explore the genetic diversity and within-host dynamics of herpesviruses (HSV) in Mormopterus francoismoutoui, a tropical insectivorous bat endemic to Reunion Island. Over three consecutive years, we collected saliva samples from seven roosts, including repeated samples from recaptured individuals. Illumina sequencing of HSV PCR-positive samples revealed a high diversity of strains (n = 20), belonging to alpha, beta and gamma-HSV subfamilies. Co-infection was frequent, with 44% of bats shedding strains from all three subfamilies. While most shedding patterns with different subfamilies appeared random, our results suggested a negative influence of gamma-HSV occurrence of the probability of co-shedding alpha-HSV. We also demonstrated a lower HSV diversity in juveniles as compared to adult bats, while pregnancy appeared to increase viral diversity--although this requires further confirmation. Longitudinal recaptures of bats revealed an accumulation of multiple HSV latent-infections over life, as the probability to be infected with a new subfamily increased with time interval between recaptures. Within-host strain dynamics were highly variable, with 79% of bats showing fluctuations in strain diversity over time--either gaining or losing strains--consistent with latency and reactivation mechanisms. These findings provide new insights into the ecological and evolutionary dynamics of herpesviruses in wild bat populations.

evolutionary biology↗

Role of individual and population heterogeneity in shaping dynamics of multi-pathogen excretion in an island endemic bat

Understanding processes driving pathogen transmission in bats is critical to prevent spillovers and emergence events. Although substantial research has addressed this topic, few studies have directly examined shedding dynamics (as opposed to serological studies) and co-infection patterns using fine-scale spatio-temporal datasets. Here, based on the monitoring of 5,714 Reunion free-tailed bats (Mormopterus francoismoutoui) in 17 roosts over 24 months, we studied the co-shedding dynamics of paramyxoviruses (PMV) and Leptospira bacteria (LEPTO) in urine, and herpesviruses (HSV) in saliva. We evidenced all year long shedding with high prevalence of all three infectious agents (37% - 87%), as well as an exceptionally high level of co-shedding (59%), with both positive and negative interactions between infectious agents. Shedding patterns displayed temporal synchrony among roosts, with a peak during summer months, but were not influenced by roost size. Repeated shedding in recaptured bats supports within-host persistence, though underlying mechanisms remain to be identified. Our results also showed rapid HSV infection of juveniles (< 6 months), and suggest longer protection of juveniles by maternal antibodies for PMV and LEPTO. Reproductive individuals (both during the pregnancy and mating) were associated to increased PMV and LEPTO shedding, which can result from tradeoffs between reproduction and infection in both sexes, and/or an age-related bias with the progressive infection of older juveniles during reproductive periods. This study highlights the significance of persistent shedding of multiple pathogens, including bacteria, and their intricate interactions within bat populations. Understanding how human-driven ecological changes may disrupt within-host processes and influence pathogen shedding in bats will help assessing the risk of pathogen spillover from bats to other species, including humans. Author summaryUnderstanding risks of bat-borne pathogen spillover is challenging because of the difficulty in studying shedding dynamics in wild bat populations. Here, we used an original island-endemic bat species to build up a fine-scale spatio-temporal shedding analysis of two viruses (paramyxoviruses and herpesviruses) and a bacterium (Leptospira) at both population- (roost) and individual- (through recaptured bats) levels. Shedding patterns are driven by the age of bats and associated to the reproductive periods in both females and males. Results also suggest that persistence, as well as interactions between infectious agents, are important within-host processes that contribute to the transmission of infections in bat populations. More research is essential to understand how human activities may influence these co-shedding patterns and the risk of cross- species transmission.

evolutionary biology↗

Linear ubiquitination at damaged lysosomes induces local NF-κB activation and controls cell survival

Lysosomes are the major cellular organelles responsible for nutrient recycling and degradation of cellular material. Maintenance of lysosomal integrity is essential for cellular homeostasis and lysosomal membrane permeabilization (LMP), induced by lysosomotrophic agents, sensitizes towards cell death. Damaged lysosomes are repaired or degraded via lysophagy, during which glycans, exposed on ruptured lysosomal membranes, are recognized by galectins leading to K48- and K63-linked poly-ubiquitination (poly-Ub) of lysosomal proteins followed by recruitment of the autophagic machinery and degradation. Linear (M1) poly-Ub, catalyzed by the E3 ligase linear ubiquitin chain assembly complex (LUBAC) and removed by the OTU domain-containing deubiquitinase with linear linkage specificity (OTULIN) exerts important functions in immune signaling and cell survival, but the role of M1 poly-Ub in lysosomal homeostasis remains largely unexplored. Here, we demonstrate that damaged lysosomes are decorated with M1 poly-Ub in a LUBAC-, OTULIN- and K63-dependent manner. LMP-induced M1 poly-Ub at damaged lysosomes contributes to lysosome degradation, recruits nuclear factor {kappa}-B (NF-{kappa}B) essential modulator (NEMO) and locally activates inhibitor of NF-B kinase (IKK) to trigger NF-{kappa}B activation in a K63 poly-Ub-dependent manner. Inhibition of lysosomal degradation enhances LMP- and OTULIN-dependent cell death, indicating pro-survival functions of LMP and potentially lysophagy. Finally, we demonstrate that M1 poly-Ub occurs at L-leucyl-leucine methyl ester (LLOMe)-damaged lysosomes in primary mouse neurons and induced pluripotent stem cell (iPSC)-derived primary human dopaminergic neurons. Together, our results reveal novel functions of M1 poly-Ub during lysosomal homeostasis, LMP and degradation of damaged lysosomes, with important implications for NF-{kappa}B signaling, inflammation and cell death.

cell biology↗

Stuck on a small tropical island: wide in-situ diversification of an urban-dwelling bat

Bats are often the only mammals naturally colonizing isolated islands and are thus an excellent model to study evolutionary processes of insular ecosystems. Here, we studied the Reunion free-tailed bat (Mormopterus francoismoutoui), an endemic species to Reunion Island that has adapted to urban settings. At regional scale, we investigated the evolutionary history of Mormopterus species, as well as on Reunion Island sex-specific and seasonal patterns of genetic structure. We used an extensive spatio-temporal sampling including 1,136 individuals from 18 roosts and three biological seasons (non-reproductive/winter, pregnancy/summer, and mating), with additional samples from Mormopterus species from neighbouring islands (M. jugularis of Madagascar and M. acetabulosus of Mauritius). Complementary information gathered from both microsatellite and mitochondrial markers revealed a high genetic diversity but no signal of spatial genetic structure and weak evidence of female philopatry. Regional analysis suggests a single colonization event for M. francoismoutoui, dated around 175,000 years ago, and followed by in-situ diversification and the evolution of divergent ancestral lineages, which today form a large metapopulation. Population expansion was relatively ancient (55,000 years ago) and thus not linked to human colonization of the island and the availability of new anthropic day-roost sites. Discordant structure between mitochondrial and microsatellite markers suggests the presence of yet-unknown mating sites, or the recent evolution of putative ecological adaptations. Our study illustrates how understanding mechanisms involved in speciation can be challenging and the importance of both mitochondrial and nuclear DNA in resolving the wide in-situ diversification of an urban-dwelling bat, endemic to a small island.

genetics↗

Migratory patterns of two major influenza virus host species on tropical islands

Animal migration is a major driver of infectious agent dispersal. Duck and seabirds migrations, for instance, play a key role in the spatial transmission dynamics and gene flows of avian influenza viruses (AIV), worldwide. On tropical islands, brown and lesser noddies (Anous stolidus and A. tenuirostris) may be important AIV hosts, but the lack of knowledge on their migratory behaviour limits our understanding of virus circulation in island networks. Here we show that high connectivity between islands generated by post-breeding behaviours could be a major driver in the spread and the maintenance of AIV among tropical islands. Tracking data highlight two types of behaviours during the non-breeding season: birds either staying in the vicinity of their breeding ground (on Bird Island, Seychelles), or moving to and roosting on other islands in the Indian Ocean. Differences in roosting places are detected between migrant birds, ranging from the Tanzanian coast to the Maldives archipelago and Tromelin Island. Epidemiological data further support that brown and lesser noddies are major hosts for AIV, although significant variation of seroprevalence between species suggest that other drivers are involved in virus infection and transmission dynamics.

ecology↗

Synchronicity of viral shedding in molossid bat maternity colonies

Infection dynamics in vertebrates are driven by biological and ecological processes. For bats, population structure and reproductive cycles have major effects on RNA virus transmission. On Reunion Island, previous studies have shown that parturition of pregnant females and aggregation of juvenile Reunion free-tailed bats (Mormopterus francoismoutoui) are associated to major increase in the prevalence of bats shedding viruses. The synchronicity of such shedding pulses, however, is yet to be assessed, between viruses but also maternity colonies. Based on 3422 fresh faeces collected every two to five weeks during four consecutive birthing seasons, we report the prevalence of bats shedding astroviruses (AstVs), coronaviruses (CoVs), and paramyxoviruses (PMVs) in two maternity colonies on Reunion Island. We found that the proportion of bats shedding viruses is highly influenced by sampling collection dates, and therefore by the seasonality of parturition. We highlight that virus shedding patterns are reproducible among years and colonies for CoVs and at a lesser extent for PMVs, but not for AstVs. We also report 1% of bats harbouring double infections, mostly CoVs and PMVs, but none shedding simultaneously AstVs, CoVs and PMVs.

ecology↗

Spectral organ fingerprints for intraoperative tissue classification with hyperspectral imaging

Visual discrimination of tissue during surgery can be challenging since different tissues appear similar to the human eye. Hyperspectral imaging (HSI) removes this limitation by associating each pixel with high-dimensional spectral information. While previous work has shown its general potential to discriminate tissue, clinical translation has been limited due to the methods current lack of robustness and generalizability. Specifically, it had been unknown whether variability in spectral reflectance is primarily explained by tissue type rather than the recorded individual or specific acquisition conditions. The contribution of this work is threefold: (1) Based on an annotated medical HSI data set (9,059 images from 46 pigs), we present a tissue atlas featuring spectral fingerprints of 20 different porcine organs and tissue types. (2) Using the principle of mixed model analysis, we show that the greatest source of variability related to HSI images is the organ under observation. (3) We show that HSI-based fully-automatic tissue differentiation of 20 organ classes with deep neural networks is possible with high accuracy (> 95 %). We conclude from our study that automatic tissue discrimination based on HSI data is feasible and could thus aid in intraoperative decision making and pave the way for context-aware computer-assisted surgery systems and autonomous robotics.

bioinformatics↗

Optimization of anastomotic technique and gastric conduit perfusion with hyperspectral imaging in an experimental model for minimally invasive esophagectomy

ObjectiveTo optimize anastomotic technique and gastric conduit perfusion with hyperspectral imaging (HSI) for total minimally invasive esophagectomy (MIE) with linear stapled anastomosis. Summary Background DataEsophagectomy is the mainstay of esophageal cancer treatment but anastomotic insufficiency related morbidity and mortality remain challenging for patient outcome. MethodsA live porcine model (n=50) for MIE was used with gastric conduit formation and linear stapled side-to-side esophagogastrostomy. Four main experimental groups differed in stapling length (3 vs. 6 cm) and anastomotic position on the conduit (cranial vs. caudal). Tissue oxygenation around the anastomotic site was evaluated using HSI and was validated with histopathology. ResultsThe tissue oxygenation ({Delta}StO2) after the anastomosis remained constant only for the short stapler in caudal position (-0.4{+/-} 4.4%, n.s.) while it dropped markedly in the other groups (short-cranial: -15.6{+/-} 11.5%, p=0.0002; long-cranial: -20.4{+/-} 7.6%, p=0.0126; long-caudal: -16.1{+/-} 9.4%, p<0.0001) Tissue samples from deoxygenated stomach as measured by HSI showed correspondent eosinophilic pre-necrotic changes in 35.7{+/-} 9.7% of the surface area. ConclusionsTissue oxygenation at the anastomotic site of the gastric conduit during MIE is influenced by stapling technique. Optimal oxygenation was achieved with a short stapler (3 cm) and sufficient distance of the anastomosis to the cranial end of the gastric conduit. HSI tissue deoxygenation corresponded to histopathologic necrotic tissue changes. These findings allow for optimization of gastric conduit perfusion and anastomotic technique in MIE. Level of EvidenceNot applicable. Translational animal science. Original article.

bioengineering↗