Mammalian Host Research Articles

Metagenomic and phylogenetic analyses reveal gene-level selection constrained by bacterial phylogeny, surrounding oxalate metabolism in the gut microbiota.

The gut microbiota is critical for neutralizing dietary toxins. Oxalate is a toxin commonly produced by plants to deter herbivory and is widely consumed in the human diet. Excess levels of systemic or urinary oxalate increase risk of multiple urologic and cardiometabolic diseases. The current study employed multiple amplicon-based and shotgun metagenomic methodologies, alongside comparative phylogenetic analyses, to interrogate evolutionary radiation surrounding microbial oxalate degradation within the human gut microbiome. In conservative genome-based estimates, over 30% of gut microbial species harbored at least one oxalate-handling gene, with the specific pathways used dependent on bacterial phylum. Co-occurrence analyses revealed interactions between specialist genes that can metabolize oxalate or its by-products, but not multi-functional genes that can act in more than one oxalate-related pathway. Specialization was rare at the genome level. Amplicon-based metagenomic sequencing of the oxalate-degrading gene, formyl-CoA transferase (frc), coupled with molecular clock phylogenetic analyses are indicative of rapid evolutionary divergence, constrained by phylum. This was corroborated by paired analyses of non-synonymous to synonymous substitutions (dN/dS ratios), which pointed toward neutral to positive selection. Sequence similarity network analyses of frc sequences suggest extensive horizontal gene transferring has occurred with the frc gene, which may have facilitated rapid divergence. The frc gene was primarily allocated to the Pseudomonodota phylum, particularly the Bradyrhizobium genus, which is a species capable of utilizing oxalate as a sole carbon and energy source. Collectively evidence provides strong support that, for oxalate metabolism, evolutionary selection occurs at the gene level, through horizontal gene transfer, rather than at the species level.IMPORTANCEA critical function of the gut microbiota is to neutralize dietary toxins, such as oxalate, which is highly prevalent in plant-based foods and is not degraded by host enzymes. However, little is known about the co-evolutionary patterns of plant toxins and the mammalian gut microbiota, which are expected to exhibit features of an evolutionary arms race. In the current work, we present molecular evidence that microbial genes for oxalate degradation are highly prevalent in humans, potentially driven by extensive horizontal gene transfer events. Phylogenetic analyses reveal that oxalate-degrading genes are under a positive selection pressure and have historically undergone rapid diversification events, which has led to diverse ecological strategies for handling oxalate by gut bacteria. Collectively, data shed light on potential evolutionary relationships between the diet and the gut microbiota that occur relatively independently of the mammalian host.

Bacteriophage-driven DNA inversions shape bacterial functionality and long-term co-existence in Bacteroides fragilis

ABSTRACT Bacterial genomic DNA inversions, which govern molecular phase-variations, provide the bacteria with functional plasticity and phenotypic diversity. These targeted rearrangements enable bacteria to respond to environmental challenges, such as bacteriophage predation, evading immune detection or gut colonization. This study investigated the short- and long-term effects of the lytic phage Barc2635 on the functional plasticity of Bacteroides fragilis, a gut commensal. Germ-free mice were colonized with B. fragilis and exposed to Barc2635 to identify genomic alterations driving phenotypic changes. Phage exposure triggered dynamic and prolonged bacterial responses, including significant shifts in phase-variable regions (PVRs), particularly in promoter orientations of polysaccharide biosynthesis loci. These shifts coincided with increased entropy in PVR inversion ratios, reflecting heightened genomic variability. In contrast, B. fragilis in control mice exhibited stable genomic configurations after gut adaptation. The phase-variable Type 1 restriction-modification system, which affects broad gene expression patterns, showed variability in both groups. However, phage-exposed bacteria displayed more restrained variability, suggesting phage-derived selection pressures. Our findings reveal that B. fragilis employs DNA inversions to adapt rapidly to phage exposure and colonization, highlighting a potential mechanism by which genomic variability contributes to its response to phage. This study demonstrates gut bacterial genomic and phenotypic plasticity upon exposure to the mammalian host and to bacteriophages.

Schmallenberg virus non-structural proteins NSs and NSm are not essential for experimental infection of Culicoides sonorensis biting midges.

The teratogenic orthobunyavirus Schmallenberg virus (SBV) is transmitted between its mammalian hosts by Culicoides biting midges. The genome of circulating SBV, i.e., variants present in viremic ruminants or insect vectors, is very stable, while variants found in malformed ruminant fetuses display a high genetic variability. It was suggested that fetal infection provides an environment that favors viral mutations that enable immune escape in the unborn but at the cost of limiting the ability of the virus to spread further. To investigate infection and dissemination rates of different SBV variants in the insect vectors, we fed laboratory-reared Culicoides sonorensis with blood containing the prototype strain BH80/11-4 from a viremic cow or strain D281/12, which was isolated from the brain of a sheep fetus and harbors multiple mutations in all three genome segments. Furthermore, virus variants lacking NSs, NSm, or both non-structural proteins were included. Six days after feeding, virus replication was found in about 2% of the midges exposed to wild-type strain BH80/11-4. The absence of the non-structural proteins had no obvious effect on the oral susceptibility to virus infection, as after 6 days, 2.78% of the midges fed with the NSs-deletion mutant displayed viral loads higher than the respective day-0 group, 1.92% of the midges exposed to the NSm-deletion mutant, and 1.55% of midges exposed to the NSs/NSm-deletion mutant. In contrast, strain D281/12 did not replicate at all in the midges, supporting the assumption that SBV variants arising in infected fetuses are unable to enter the normal insect-mammalian host cycle.IMPORTANCEBiting midges are responsible for the transmission of Schmallenberg virus (SBV), a pathogen of veterinary importance that primarily infects ruminants. Although SBV has been extensively studied in the mammalian host, the virus-intrinsic factors allowing infection of and replication in biting midges are largely unknown. Therefore, we infected laboratory-reared Culicoides sonorensis midges with SBV variants by feeding them virus-containing blood. The SBV variants differed in their genome composition, as we used the prototype wild-type strain, a strain with multiple mutations that was isolated from the brain of a malformed fetus, and recombinants lacking either NSs or NSm or both of these non-structural proteins. While the non-structural proteins had no obvious effect, the variant from the malformed fetus did not replicate at all, indicating that virus variants with characteristic genomic mutations present in fetuses lose their ability to infect the insect vector and will be excluded from the natural transmission cycle.

Sarcoendoplasmic reticulum calcium ATPase is an essential and druggable lipid-dependent ion pump in Toxoplasma gondii

Toxoplasma gondii is a common intracellular pathogenic protist causing acute and chronic infections in many warm-blooded organisms. Calcium homeostasis is pivotal for its asexual reproduction in mammalian host cells, and sarcoendoplasmic reticulum calcium-ATPase (SERCA) is considered vital for maintaining ion homeostasis within the parasite. This work studied the physiological relevance, structure-function relationship, mechanism, and therapeutic value of SERCA in the acutely-infectious tachyzoite stage of T. gondii. A conditional depletion of SERCA, located in the endoplasmic reticulum, by auxin-inducible degradation is lethal for the parasite due to severe defects in its replication, gliding motility, and invasion. The observed phenotypes are caused by dysregulated calcium ion homeostasis and microneme secretion in the absence of TgSERCA. Furthermore, ectopic expression of TgSERCA restored the lytic cycle of a phosphatidylthreonine-null and phosphatidylserine-enriched mutant with perturbed calcium homeostasis, motility and invasion. These lipids are expressed in the parasite ER, co-localizing with TgSERCA. Last but not least, the structure-function modeling and ligand docking of TgSERCA with a library comprising >5000 chemicals identified two compounds (RB-15, NR-301) that inhibited the lytic cycle by affecting the tachyzoite locomotion, invasion, microneme discharge, and calcium levels. In conclusion, we demonstrate TgSERCA as an indispensable lipid-assisted calcium pump in T. gondii and report small molecules with therapeutic potential against toxoplasmosis.

First Report on the Molecular Detection and Characterization of Rickettsia felis in Laelapidae (Acari: Mesostigmata) Mites in Malaysia

Rickettsiae are Gram-negative and obligate intracellular bacteria that cause rickettsioses. These pathogens are typically transmitted by arthropod vectors, such as ticks, mesostigmatid mites, and fleas. Rickettsiae are responsible for many emerging infectious diseases worldwide and are the second most frequently reported cause of non-malarial febrile illnesses in Southeast Asia. However, in Malaysia, studies on the prevalence and distribution of rickettsiae have primarily focused on humans, with limited data on these bacteria in vectors and small mammal hosts. Thus, this study aims to investigate the presence of Rickettsia spp. in small mammals and their associated mesostigmatid mites collected from potential rickettsioses areas in Selangor. Animal trapping was conducted across three different ecological study sites comprising a recreational area, agricultural land, and coastal area. A total of 41 small mammals and 363 mesostigmatid mites were collected and identified. Ten percent of the total individual mites were processed for morphological examination, and the remaining mites were then pooled by hosts, with five individual mites per tube, for DNA extraction. The collected samples, comprising blood, animal tissue, and pooled mites, were subjected to DNA extraction and were screened for Rickettsia spp. via nested polymerase chain reaction (PCR), targeting the citrate synthase-encoding gene (gltA) and outer membrane protein B gene (ompB). Interestingly, two pools (3.33%) of Laelaps spp. recovered from Maxomys whiteheadi and Bandicota indica, collected from a recreational area, tested positive for Rickettsia spp. Sequence analysis and phylogenetic tree of the ompB gene revealed the presence of Rickettsia felis in both laelapid mite pools. To our knowledge, this study provides the first molecular detection of R. felis in Laelaps spp. in Malaysia.

Cytokines from parasites: manipulating host responses by molecular mimicry.

Helminth parasites have evolved sophisticated methods for manipulating the host immune response to ensure long-term survival in their chosen niche, for example, by secreting products that interfere with the host cytokine network. Studies on the secretions of Heligmosomoides polygyrus have identified a family of transforming growth factor-β (TGF-β) mimics (TGMs), which bear no primary amino acid sequence similarity to mammalian TGF-β, but functionally replicate or antagonise TGF-β effects in restricted cell types. The prototypic member, TGM1, induces in vitro differentiation of Foxp3+ T regulatory cells and attenuates airway allergic and intestinal inflammation in animal models. TGM1 is one of a family of ten TGM proteins expressed by H. polygyrus. It is a five-domain modular protein in which domains 1-2 bind TGFBR1, and domain 3 binds TGFBR2; domains 4-5 increase its potency by binding a co-receptor, CD44, highly expressed on immune cells. Domains 4-5 are more diverse in other TGMs, which bind co-receptors on cells such as fibroblasts. One variant, TGM6, lacks domains 1-2 and hence cannot transduce a signal but binds TGFBR2 through domain 3 and a co-receptor expressed on fibroblasts through domains 4-5 and blocks TGF-β signalling in fibroblasts and epithelial cells; T cells do not express the co-receptor and are not inhibited by TGM6. Hence, different family members have evolved to act as agonists or antagonists on various cell types. TGMs, which function by molecularly mimicking binding of the host cytokine to the host TGF-β receptors, are examples of highly evolved immunomodulators from parasites, including those that block interleukin (IL)-13 and IL-33 signalling, modulate macrophage and dendritic cell responses and modify host cell metabolism. The emerging panoply and potency of helminth evasion molecules illustrates the range of strategies in play to maintain long-term infections in the mammalian host.

Exploring Avian Influenza Viruses in Yakutia—The Largest Breeding Habitat of Wild Migratory Birds in Northeastern Siberia

Yakutia, the largest breeding ground for wild migratory birds in Northeastern Siberia, plays a big role in the global ecology of avian influenza viruses (AIVs). In this study, we present the results of virological surveillance conducted between 2018 and 2023, analyzing 1970 cloacal swab samples collected from 56 bird species. We identified 74 AIVs of H3N6, H3N8, H4N6, H5N3, H7N7, H10N3, and H11N9 subtypes in Anseriformes order. Phylogenetic analysis showed that the isolates belong to the Eurasian lineage and have genetic similarities with strains from East Asia, Europe, and North America. Cluster analysis has demonstrated the circulation of stable AIV genotypes for several years. We assume that Yakutia is an important territory for viral exchange on the migratory routes of migrating birds. In addition, several amino acid substitutions have been found to be associated with increased virulence and adaptation to mammalian hosts, highlighting the potential risk of interspecific transmission. These results provide a critical insight into the ecology of the AIV and highlight the importance of continued monitoring in this geographically significant region.

Global prevalence of Giardia infection in nonhuman mammalian hosts: A systematic review and meta-analysis of five million animals.

Members of the Giardia genus are zoonotic protozoan parasites that cause giardiasis, a diarrheal disease of public and veterinary health concern, in a wide range of mammal hosts, including humans. We conducted a systematic review and meta-analysis to provide evidence-based data on the worldwide prevalence of Giardia infection in nonhuman mammals that can be used as scientific foundation for further studies. We searched public databases using specific keywords to identify relevant publications from 1980 to 2023. We computed the pooled prevalence estimates utilizing a random-effects meta-analysis model. Animals were stratified according to their taxonomic hierarchy, as well as ecological and biological factors. We investigated the influence of predetermined variables on prevalence estimates and heterogeneity through subgroup and meta-regression analyses. We conducted phylogenetic analysis to examine the evolutionary relationships among different assemblages of G. duodenalis. The study included 861 studies (1,632 datasets) involving 4,917,663 animals from 327 species, 203 genera, 67 families, and 14 orders from 89 countries. The global pooled prevalence of Giardia infection in nonhuman mammals was estimated at 13.6% (95% CI: 13.4-13.8), with the highest rates observed in Rodentia (28.0%) and Artiodactyla (17.0%). Herbivorous (17.0%), semiaquatic (29.0%), and wild (19.0%) animals showed higher prevalence rates. A decreasing prevalence trend was observed over time (β = -0.1036477, 95% CI -0.1557359 to -0.0515595, p < 0.000). Among 16,479 G. duodenalis isolates, 15,999 mono-infections belonging to eight (A-H) assemblages were identified. Assemblage E was the predominant genotype (53.7%), followed by assemblages A (18.1%), B (14.1%), D (6.4%), C (5.6%), F (1.4%), G (0.6%), and H (0.1%). The highest G. duodenalis genetic diversity was found in cattle (n = 7,651, where six assemblages including A (13.6%), B (3.1%), C (0.2%), D (0.1%), E (81.7%), and mixed infections (1.2%) were identified. Domestic mammals are significant contributors to the environmental contamination with Giardia cysts, emphasizing the importance of implementing good management practices and appropriate control measures. The widespread presence of Giardia in wildlife suggests that free-living animals can potentially act as speeders of the infection to livestock and even humans through overlapping of sylvatic and domestic transmission cycles of the parasite.

Molecular and ecological determinants of mammalian adaptability in avian influenza virus.

The avian influenza virus (AIV) primarily affects birds and poses an increasing concern due to its growing adaptability to other hosts, heightening zoonotic risks. The adaptability is a key factor in AIV to infect multiple non-avian species, including humans, companion animals, aquatic mammals, carnivores, and other mammals. The virus is evolving through genetic mutations and reassortments, leading to the emergence of AIV strains with enhanced virulence and adaptability in mammals. This highlights the critical need to understand the genetic factors of AIV, including mutations in polymerase proteins, surface antigens, and other regulatory proteins, as well as the dynamics of AIV-host interactions and environmental factors such as temperature, humidity, water salinity, and pH that govern the cross-species adaptability of the virus. This review provides comprehensive insights into the molecular/genetic changes AIV undergoes to adapt in mammalian hosts including bovines, swine, equines, canines, and felines. The adaptive mutations in viral polymerase proteins, such as PB2-E627K, and receptor specificity shift facilitate the virus adaptability in mammals. Since AIVs interact with specific receptors on host cells, therefore the type and distribution of receptors are crucial in determining the host range of the virus and its adaptability by facilitating attachment and entry of the virus. This review examines sialic acid receptor distribution and binding patterns in various mammalian hosts, emphasizing how the presence and structure of specific receptors influence viral interaction, adaptation, and transmission. The review concludes that the differential distribution and expression of SA receptors are vital in the mammalian adaptability and tissue tropism of viral strains. Notably, during the adaptation to mammals, AIVs show a shift in preference from α-2,3 to α-2,6 receptors. This review further emphasizes the role of ecological determinants in the adaptation of viruses to mammalian hosts. Low temperatures, high humidity, and neutral to slightly acidic pH levels enhance virus stability, facilitating its persistence in the environment and spread among susceptible hosts. Overall, AIV remains a global health threat, necessitating coordinated efforts in research, surveillance, and public health strategies.

TblncRNA-23, a long non-coding RNA transcribed by RNA polymerase I, regulates developmental changes in Trypanosoma brucei

The protozoan parasite Trypanosoma brucei undergoes a complex life cycle, moving between its mammalian host and the blood-feeding tsetse fly vector. The two major surface proteins expressed by procyclic forms in the insect midgut, EP and GPEET procyclin, are transcribed from a polycistronic transcription unit by RNA polymerase I. Here we identify a long non-coding RNA, TblncRNA-23, that is encoded between the two procyclin genes. TblncRNA-23 localizes to the nucleolus and also associates with polysomes. Overexpression of TblncRNA-23 and its down regulation by RNAi or knockout (KO) identify EP and GPEET mRNAs as targets, among other mRNAs that changed abundance in the transition from early to late procyclic forms and from procylic to the metacylic forms, suggesting its role in regulating gene expression which accomapines or dictates of the parasite transitions within in its insect host. TblncRNA-23 interacts with its substrates via base-pairing using different domains. Purification of TblncRNA-23-associated proteins by RaPID identifies hundreds of proteins, including proteins translated from its target mRNAs, suggesting its association with translating ribosomes. Early and late procyclic forms differ in their social motility (SoMo) capabilities, which is essential for migration away from the insect midgut to enable parasite transmission. Overexpression of TblncRNA-23 results in hypermotility, whereas KO compromises this capacity, suggesting a regulatory role in SoMo. Moreover, silencing of the RNA abrogates the ability of the parasite to transform from procylic to the metacyclic forms affecting the parasite’s potential to cycle between its hosts.

Trypanosoma cruzi/Triatomine Interactions-A Review.

This review summarizes the interactions between Trypanosoma cruzi, the etiologic agent of Chagas disease, and its vectors, the triatomines, and highlights open questions. Four important facts should be emphasized at the outset: (1) The development of T. cruzi strains and their interactions with the mammalian host and the insect vector vary greatly. (2) Only about 10 of over 150 triatomine species have been studied for their interactions with the protozoan parasite. (3) The use of laboratory strains of triatomines makes generalizations difficult, as maintenance conditions influence the interactions. (4) The intestinal microbiota is involved in the interactions, but the mutualistic symbionts, Actinomycetales, have so far only been identified in four species of triatomines. The effects of the vector on T. cruzi are reflected in a different colonization ability of T. cruzi in different triatomine species. In addition, the conditions in the intestine lead to strong multiplication in the posterior midgut and rectum, with infectious metacyclic trypomastigotes developing almost exclusively in the latter. Starvation and feeding of the vector induce the development of certain stages of T. cruzi. The negative effects of T. cruzi on the triatomines depend on the T. cruzi strain and are particularly evident when the triatomines are stressed. The intestinal immunity of the triatomines responds to ingested blood-stage trypomastigotes of some T. cruzi strains and affects many intestinal bacteria, but not all and not the mutualistic symbionts. The specific interaction between T. cruzi and the bacteria is evident after the knockdown of antimicrobial peptides: the number of non-symbiotic bacteria increases and the number of T. cruzi decreases. In long-term infections, the suppression of intestinal immunity is indicated by the growth of specific microbiota.

Climatic variations and Yersinia pestis host-vector abundance: a case study in Ankazobe district to understand plague epidemiology in Madagascar

BackgroundPlague, a disease caused by the bacterium Yersinia pestis remains a major public health concern in Madagascar despite numerous multidisciplinary studies. The persistence of human plague infections is thought to be linked to fluctuations in mammalian host and flea populations, which are affected by climatic and environmental variations. This study explored local macro- and microclimatic variations along with mammal and flea population dynamics across different microhabitat types within plague endemic rural and forested habitats of Madagascar. Understanding these variables and their interdependent relationships may help us better understand the complexities of Y. pestis transmission in the Madagascan Highlands.MethodsSmall mammals and their fleas were captured in different microhabitats within plague focus in the Ankazobe District of Madagascar. Simultaneously, climatic data including temperature and humidity, were collected to assess the potential relationship between flea population dynamics and climatic variations. Specialized equipment was used to monitor microclimate conditions across various microhabitat types and compare them with macroclimate. Monitoring was performed inside and outside rodent burrows located inside and outside houses and in adjacent forested areas.ResultsA greater abundance of fleas was observed inside dwellings compared to other microhabitats, such as outside houses and forest, whereas small mammal species diversity was significantly higher in forest environments. We also revealed significant differences in microclimates across microhabitat types, with lower temperatures and higher humidity inside rodent burrows compared to outside burrows, outside houses and the forest. Inside houses, temperature variations were more stable although temperatures were higher and humidity lower inside rodent burrows compared to other microhabitats.ConclusionThis study highlights microclimate variation across different microhabitat types, which also differ from the macroclimate, and maps small mammal and flea abundance to these locations. These data suggest that it is important to further explore the relationship between microclimatic variations in the different microhabitats and the dynamics of flea and rodent populations as potential markers for plague persistence and transmission in these endemic foci.

Host Trait-Based Patterns of Parasite Species Co-occurrence in Component Communities: A Case Study With Fleas Parasitic on Small Mammals.

We applied a novel eigenvector ellipsoid method to investigate patterns of flea species co-occurrences on small mammalian hosts from six biogeographic realms. We asked whether the application of this method that links host trait-associated requirements of flea species (represented by eigenvector ellipsoids based on the traits of hosts exploited by them) with their among-host distribution would allow us to detect the same patterns as those identified by traditional methods for detecting non-randomness in species co-occurrences. We also asked whether (a) congeneric and heterogeneric species pairs differ in their pairwise pattern of co-occurrence and (b) the patterns of flea species co-occurrences in regional compound communities are associated with the regions' environmental characteristics. Although flea species seem to be randomly associated in the majority of communities, the values of average ellipsoid overlap suggested different degrees of species aggregation rather than segregation. Clear patterns of nestedness and modularity, in among-host flea distribution, were detected in a few communities only. Congeneric species pairs showed higher ellipsoid overlap and longer distances between their centroids than heterogeneric pairs. The relationship between the overlap of host-associated flea niches in a region and regional precipitation was either positive or negative, depending on the realm. The results of the application of the eigenvector ellipsoid method appeared to be more reliable than those produced by traditional methods, which overestimated the degree of species aggregation and underestimated differences in co-occurrence patterns between conspecific and heterogeneric species pairs.

Rickettsia rickettsii RoaM negatively regulates expression of a limited number of rickettsial genes.

RoaM was previously shown to repress the production of actin tails by unknown mechanisms. The roaM gene is negatively selected for in cell culture resulting in hyper-spreading mutants. This work reveals that rather than specifically regulating motility in Rickettsia rickettsii, a set of rickettsial genes is downregulated that includes the type IV secreted effector, rarP2, as well as two other secreted, putative effectors. Relatively few secreted effectors have been identified in Rickettsia. RoaM appears to be part of a larger biological program encompassing active spreading in mammalian cells and may be a critical component for R. rickettsii to transition from arthropod to mammalian host.

Divergent dimerization mechanisms and conserved DNA-binding function in PFam12 proteins of Borrelia burgdorferi

Lyme disease, caused by the spirochete Borrelia burgdorferi, is transmitted to mammalian hosts during the feeding process of infected Ixodes ticks. Our previous studies demonstrated that the paralogous gene family 12 (PFam12) consisting of five members (BBK01, BBG01, BBH37, BBJ08, and BB0844) are non-specific DNA-binding proteins. PFam12 proteins share 31–69% sequence identity, are located either on the surface or within the periplasm and are upregulated as the tick starts its blood meal. The crystal structure of BBK01 revealed that the protein forms a homodimer, which is potentially critical for DNA binding. In this study, we determined the crystal structure of another PFam12 member, BBH37, to gain a better insight into this unique paralogous family. Although BBK01 dimerization is mediated by its C-terminal region and is thought to be critical for DNA binding, BBH37 forms dimers through an alternative mechanism where a unique disulfide bond is involved. We found that BBH37 is still able to interact with DNA with micromolar affinity. Molecular dynamics simulations and site-directed mutagenesis was conducted to characterize these unique DNA binding proteins. This study highlights the structural diversity within the PFam12, demonstrating that despite significant differences in dimerization mechanisms, these proteins retain their DNA-binding capability.

Vitamin biosynthesis in the gut: interplay between mammalian host and its resident microbiota.

SUMMARYIn recent years, exhaustive efforts have been made to dissect the composition of gut-associated microbial communities and associated interactions with their human host, which are thought to play a crucial role in host development, physiology, and metabolic functions. Although such studies were initially focused on the description of the compositional shifts in the microbiota that occur between different health conditions, more recently, they have provided key insights into the functional and metabolic contributions of the gut microbiota to overall host physiology. In this context, an important metabolic activity of the human gut microbiota is believed to be represented by the synthesis of various vitamins that may elicit considerable benefits to human health. A growing body of scientific literature is now available relating to (predicted) bacterial vitamin biosynthetic abilities, with ever-growing information concerning the prevalence of these biosynthetic abilities among members of the human microbiota. This review is aimed at disentangling if and how cooperative trophic interactions of human microbiota members contribute to vitamin production, and if such, gut microbiota-mediated vitamin production varies according to different life stages. Moreover, it offers a brief exploration of how different diets may influence vitamin production by shaping the overall composition and metabolic activity of the human gut microbiota while also providing preliminary insights into potential correlations between human microbiota-associated vitamin production and the occurrence of human diseases and/or metabolic disorders.

Moonlighting enzymes of Borrelia burgdorferi.

Moonlighting enzymes are increasingly recognized in bacteria with dual functions depending on whether they are intracellular or expressed on the surface. Enzymes of the glycolytic pathway are among the most frequently associated with moonlighting functions and lack the signal sequences needed to deliver them to the cell surface. Once these enzymes are on the surface, they perform functions that are associated with pathogenesis and development of infection through interaction with host substrates. One such interaction is adhesion. Borrelia burgdorferi, the etiologic agent of Lyme disease, must encounter a wide number of different tissues and substrates from ticks to mammalian hosts to complete its life cycle and persist. The phosphomannose isomerase of this organism has a moonlighting function, interacting with collagen IV, a main component of the basal lamina. It is abundant in the skin, which is the site of the initial infection of B. burgdorferi.

Fasciola hepatica in donkeys from southern Texas, USA.

Fasciola hepatica in donkeys from southern Texas, USA.

Receptor-regulated smads (R-Smads) in the liver fluke Fasciola gigantica: Characterization, comparative sequence analysis, and life stage-specific expression.

Receptor-regulated smads (R-Smads) in the liver fluke Fasciola gigantica: Characterization, comparative sequence analysis, and life stage-specific expression.

A global-scale dataset of bat viral detection suggests that pregnancy reduces viral shedding.

Understanding viral infection dynamics in wildlife hosts can help forecast zoonotic pathogen spillover and human disease risk. Bats are important reservoirs of zoonotic viruses, and bat metapopulation dynamics, seasonal reproductive patterns and other life-history characteristics might explain temporal variation in the spillover of bat-associated viruses. Here, we analyse reproductive effects on viral dynamics in free-ranging bat hosts, leveraging a multi-year, global-scale viral detection dataset that spans eight viral families and 96 bat species from 14 countries. Bayesian models revealed that pregnancy had a negative effect on viral shedding across multiple data subsets, and this effect was robust to different model formulations. By contrast, lactation had a weaker influence that was inconsistent across models. These results are unusual for mammalian hosts, but given recent findings that bats may have high individual viral loads and population-level prevalence due to dampening of antiviral immunity, we propose that it would be evolutionarily advantageous for pregnancy to either not further reduce immunity or actually increase the immune response, reducing viral load, shedding and risk of fetal infection. This novel hypothesis would be valuable to test given its potential to help monitor, predict and manage viral spillover from bats.