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bioRxiv2024

Determination and characterization of papillomaviurs and parvovirus causing mass mortality of Chinese tongue sole (Cynoglossus semilaevis) in China

Chinese tongue sole (Cynoglossus semilaevis) is one of the representative species in flatfish aquaculture in China. In recent years, massive mortality of farmed Chinese tongue soles occurred in Tianjin, China. The causative pathogens were determined as Cynoglossus semilaevis papillomavirus (CsPaV) and parvovirus (CsPV) by electron microscopy, virus isolation, experimental challenge, histopathological analysis, genome sequencing, fluorescence In situ hybridization (FISH) and epidemiology investigation. Electron microscopy showed large numbers of spherical non-enveloped virus particles presenting in liver, kidney, spleen, gill and heart of the diseased fish. The viruses were isolated and propagated in flounder gill cells (FG) and induced a typical cytopathic effect (CPE). The cumulative mortality reached 100% at 8 dpi by intraperitoneal injection. The complete genome of CsPaV and CsPV was 5939 bp and 3663 bp in size respectively, and both viral genomes shared no nucleotide sequence similarity with other viruses. The CsPaV contained seven predicated protein coding regions (E1, E2, L2, L1a, L1b, sORF1 and sORF2) and CsPV contained three predicated protein coding regions (NS1, VP and ORF3). Phylogenetic analysis basing on L1 and NS1 protein sequences revealed that CsPaV and CsPV are novel members belonging to new genus in Papillomaviridae and Parvoviridae family. FISH results showed positive signals in spleen and kidney tissues from CsPaV and CsPV infected fish and the two viruses could co-infected one cell. Epidemiological investigation showed that the two viruses cocurrented in 82.9% sampled fish and they were proved to be the pathogenic agents of the emerging disease in farmed Chinese tongue soles in China. This study represents the first report of co-infection of papillomavirus and parvovirus in farmed fish and provides a basis for further studies on prevention and treatment of the emerging viral disease, and also represents clues to elucidate the the mechanisms of viruses co-infection and evolution of viruses. Author summaryChinese tongue sole is a valuable fish kept in marincultures. Outbreak of an emerging disease caused massive mortality and resulted in significant economic loss. The pathogenic agent remains unknown. In this study, we identified papillomavirus (CsPaV) and parvovirus (CsPV) from the diseased fish simultaneously, and they are proved to be novel members belonging to new genus in Papillomaviridae and Parvoviridae family. It was shown that the emerging disease was caused by co-infection with the two viruses. Viral co-infections are widespread in nature, however, studies and available data on viral co-infections in fish aquaculture are limited. Our findings represent new clues to elucidate the mechanisms of viruses co-infection and evolution of viruses, and moreover, the present study provide a solution for the control of emerging viral diseases in Chinese tongue sole.

microbiology↗

bioRxiv2024

Genotyping of Leptospira spp. in wild rats leads to first time detection of L. kirshneri serovar Mozdok in Serbia

This study aimed to investigate the prevalence and molecular characterization of Leptospira species in Belgrade, Serbia, an area where this disease is underexplored. Specifically, the study sought to employ molecular and multilocus sequence typing analyses to fill the gap in understanding the diversity and distribution of Leptospira species within the region. A comprehensive molecular analysis was conducted on kidney samples obtained from Norway rats (Rattus novegicus) in urban environments. The study utilized molecular diagnostic techniques including real-time PCR targeting the lipL32 gene and performing sequence-based typing schemes utilizing adk, icdA, lipL32, lipL41, rrs2 and secY genes. These methodologies were applied to ascertain the presence and characterize different Leptospira species and serotypes, respectively. The findings revealed the presence of two Leptospira species and three separate serotypes in the Belgrade area. Moreover, this study identified the presence of L. kirschneri serovar Mozdok in Serbia for the first time, a significant discovery previously undocumented in the region. This pioneering investigation sheds light on the molecular diversity and prevalence of Leptospira species in Serbia. The study underscores the importance of employing molecular typing methods to gain insights into the epidemiology and characterization of Leptospira species. These findings significantly contribute to both local and global perspectives on leptospirosis epidemiology, providing vital insights for the development of effective control strategies and interventions. Author summaryIn our recent study, we explored the presence and performed molecular typing of the Leptospira species, the bacteria responsible for leptospirosis, in wild rats in Serbia. This was the first time such a study was conducted in the region. Leptospirosis is a serious disease that affects both animals and humans, often transmitted through contact with water contaminated by infected animals. Our focus was on understanding which types of Leptospira were present in these animals. Excitingly, we discovered a particular strain of Leptospira, known as L. kirshneri serovar Mozdok, for the first time in Serbia. This finding is significant because it sheds light on the presence and spread of different Leptospira serovars in Serbia. It also raises awareness about the potential health risks associated with this serovar, which was previously unknown in the area. Our work fits into a broader context of disease surveillance and public health. By identifying the types of Leptospira present in a specific region, we can better understand the risks to public health and take steps to prevent and control the spread of leptospirosis. This discovery is not just important for scientists studying infectious diseases; it has real implications for public health officials, veterinarians, and anyone concerned with preventing and treating leptospirosis. Our findings highlight the need for ongoing monitoring of Leptospira in wildlife, to protect both animal and human health.

microbiology↗

bioRxiv2024

West Nile virus is transmitted within mosquito populations through infectious mosquito excreta

Understanding transmission routes of arboviruses is key to control their epidemiology and global health burden. Using West Nile virus and Culex mosquitoes, we tested whether arboviruses are transmitted through mosquito excreta. First, we determined the presence of infectious virions in excreta and quantified a high concentration of infectious units per excreta. Second, we showed that virion excretion starts early after oral infection and remains constant for a long period, regardless of mosquito infection level. These results highlight the infectiousness of excreta from infected mosquitoes. Third, we found that both larvae and pupae were susceptible to infection, although pupae were highly permissive. Forth, we established the proof-of-concept that immature mosqui-toes can be infected by infectious excreta, demonstrating a new excreta-mediated mode of transmission. Finally, by mathematically modelling excreta-mediated transmission in the field, we demonstrated its potential impact on arbovirus epidemiology. Our study uncovers a new route of transmission for arboviruses, unveiling mechanisms of viral maintenance in mosquito reservoirs and of vector species shift that contribute to zoonotic emergence.

zoology↗

bioRxiv2024

Presence of phage-plasmids in multiple serovars of Salmonella enterica

Evidence is accumulating in the literature that the horizontal spread of antimicrobial resistance (AMR) genes mediated by bacteriophages and bacteriophage-like plasmid (phage-plasmid) elements is much more common than previously envisioned. For instance, we recently identified and characterised a circular P1-like phage-plasmid harbouring a blaCTX-M-15 gene conferring extended-spectrum beta-lactamase (ESBL) resistance in Salmonella enterica serovar Typhi. As the prevalence and epidemiological relevance of such mechanisms has never been systematically assessed in Enterobacterales, in this study we carried out a follow-up retrospective analysis of UK Salmonella isolates previously sequenced as part of routine surveillance protocols between 2016 and 2021. Using a high-throughput bioinformatics pipeline we screened 47,784 isolates for the presence of the P1 lytic replication gene repL, identifying 226 positive isolates from 25 serovars and demonstrating that phage-plasmid elements are more frequent than previously thought. The affinity for phage-plasmids appears highly serovar-dependent, with several serovars being more likely hosts than others; most of the positive isolates (170/226) belonged to S. Typhimurium ST34 and ST19. The phage-plasmids ranged between 85.8-98.2kb in size, with an average length of 92.1kb; detailed analysis indicated a high amount of diversity in gene content and genomic architecture. 132 phage-plasmids had the p0111 plasmid replication type, and 94 the IncY type; phylogenetic analysis indicated that both horizontal and vertical gene transmission mechanisms are likely to be involved in phage-plasmid propagation. Finally, phage-plasmids were present in isolates that were resistant and non-resistant to antimicrobials. In addition to providing a first comprehensive view of the presence of phage-plasmids in Salmonella, our work highlights the need for a better surveillance and understanding of phage-plasmids as AMR carriers, especially through their characterisation with long-read sequencing. Data SummaryAll of the FASTQ files examined in this study have been uploaded to the Sequence Read Archive under BioProject PRJNA248792. Accessions of individual isolates which were found to contain phage plasmids are listed in Supplementary Table S1. Impact StatementBacteriophage-like plasmids are increasingly being recognised as important mobile elements in many species of bacteria, particularly due to their involvement in the transmission of antimicrobial resistance (AMR); however, few studies of their overall prevalence in clinical datasets have been undertaken to date. In this study we have performed the first large-scale surveillance of human disease-associated Salmonella genomes for the presence of P1-like phage-plasmids, showing that they are more common than previously thought. Furthermore, we highlight how valuable information about the evolution and transmission of phage-plasmids in Salmonella and other Enterobacterales can be revealed by linking phage-plasmid prevalence and genetic diversity to epidemiologically relevant metadata such as S. enterica serovar, outbreak clusters, time, and geography. Our work shows the ability to use sequencing data and scalable bioinformatics workflows for the detection and characterisation of these extrachromosomal elements, highlights the importance of screening for novel mechanisms of AMR transmission, and provides a foundation for further surveillance studies of phage-plasmid prevalence.

microbiology↗

bioRxiv2024

The Fossilised Birth-Death Model is Identifiable

Time-dependent birth-death sampling models have been used in numerous studies for inferring past evolutionary dynamics in different areas, e.g. speciation and extinction rates in macroevolutionary studies, or effective reproductive number in epidemiological studies. These models are branching processes where lineages can bifurcate, die, or be sampled with time-dependent birth, death, and sampling rates, generating phylogenetic trees. It has been shown that in some subclasses of such models, different sets of rates can result in the same distributions of reconstructed phylogenetic trees, and therefore the rates become unidentifiable from the trees regardless of their size. Here we show that widely used time-dependent fossilised birth-death (FBD) models are identifiable. This subclass of models makes more realistic assumptions about the fossilisation process and certain infectious disease transmission processes than the unidentifiable birth-death sampling models. Namely, FBD models assume that sampled lineages stay in the process rather than being immediately removed upon sampling. Identifiability of the time-dependent FBD model justifies using statistical methods that implement this model to infer the underlying temporal diversification or epidemiological dynamics from phylogenetic trees or directly from molecular or other comparative data. We further show that the time-dependent fossilised-birth-death model with an extra parameter, the removal after sampling probability, is unidentifiable. This implies that in scenarios where we do not know how sampling affects lineages we are unable to infer this extra parameter together with birth, death, and sampling rates solely from trees.

evolutionary biology↗

bioRxiv2024

Experimental assessment of marine microbial interactions: from predatory protists promoting bacterial survival to bacterial lysis of the protists

Bacteria in aquatic environments are a principal food source for predatory protists. Whereas interactions between bacteria and protists are recognized to play important roles in determining the pathogenesis and epidemiology of several human pathogens, few studies have systematically characterized the interactions between specific aquatic bacteria and protists beyond the prey-predator relation. We therefore surveyed the outcome of individual co-cultures between 18 different genome-sequenced marine bacteria with known virulence gene repertoires and three model protist species widely used for assessing bacteria-protist interactions. Strikingly, ten, five, and three bacterial isolates were capable of lysing the protists Acanthamoeba polyphaga, Tetrahymena pyriformis and Euglena gracilis, respectively. A majority of the bacteria were able to grow and/or maintain viable populations in the presence of viable protists. Some bacteria survived longer in the presence of viable protists but not heat-killed protists, and were observed in protist vacuoles. In this respect, thus, marine bacteria are similar to several protist-dependent human pathogens, including Legionella. Analyses of growth patterns in low-nutrient media showed that co-cultivation with A polyphaga allowed one bacterial strain to overcome nutritional stress and obtain active growth. Five isolates depended on viable amoebae to grow, notwithstanding nutrient media status. The remarkable capability of surviving encounters with, and even actively killing, bacterivorous protists, indicates that diverse (and possibly novel) bacterial defense strategies and virulence mechanisms to access nutrients are widespread among marine bacteria. The diversity of interactions uncovered here has important implications for understanding ecological and evolutionary consequences of population dynamics in bacteria and protists. IMPORTANCEThe microbiome constitutes the base of food webs in marine waters. Its composition partly reflects biotic interactions, where bacteria primarily are considered as prey of predatory protists. However, studies that focus on one or a few species have shown that some bacteria have abilities to escape grazing and may even be capable of lysing their protist predators. In this study, we substantially extend these findings by systematically investigating interactions among multiple taxa of both bacteria and protists. Our results show that marine bacteria display a wider and more complex range of interactions with their predators than generally recognized - from growth dependency to protist lysis. Given that such interactions play key roles in the pathogenesis and epidemiology of several human pathogens, our findings imply that bacterial virulence traits can contribute to defining the structure and ecology of the marine microbiome.

microbiology↗

bioRxiv2024

Combining single-gene-resistant and pyramided cultivars in agricultural landscape compromises the benefits of pyramiding in most, but not all, productions situations

ContextWhile resistant cultivars are valuable in safeguarding crops against diseases, they can be rapidly overcome by pathogens. Numerous strategies have been proposed to delay pathogen adaptation (evolutionary control), while still ensuring effective protection (epidemiological control). Resistance genes can be deployed in 1) single-gene-resistant cultivars sown in the same field (mixture strategy) or in different fields (mosaic strategy), 2) a pyramided cultivar (pyramiding strategy) or 3) hybrid strategies that combine the three previous strategies. In addition, the spatial scale at which resistant cultivars are deployed can affect the plant-pathogens interaction: small fields are thought to reduce pest density and disease transmission. ObjectivesWe aim to compare these strategies, focusing on the effects of the simultaneous deployment of single-gene-resistant and pyramided cultivars sharing resistance genes in an agricultural landscape. We also investigate the impact of field size. MethodsWe used the spatially-explicit stochastic model landsepi to compare the evolutionary and epidemiological control across spatial scales and deployment strategies for two major resistance genes. ResultsThe evolutionary control provided by the pyramiding strategy is at risk when single-gene-resistant cultivars are concurrently planted in the landscape (hybrid strategies). The probabilities of pathogen mutation and the corresponding fitness costs play a crucial role in determining the feasibility of planting pyramided cultivars alongside single-gene-resistant ones. Instead, field size did not affect strategies recommendation. ConclusionsPlanting pyramided cultivars alongside single-gene-resistant ones should be avoided. Socio-economic perspectives for the adoption of resistance management strategies are discussed.

evolutionary biology↗

bioRxiv2024

High density genomic surveillance and risk profiling of clinical Listeria monocytogenes subtypes in Germany, 2018-2021

AO_SCPLOWBSTRACTC_SCPLOWFoodborne infections represent a significant public health concern, particularly when outbreaks affect many individuals over prolonged time. Systematic collection of pathogen isolates from infected patients, whole genome sequencing and phylogenetic analyses allow recognition and termination of outbreaks after source identification and risk profiling of abundant lineages. We here present a multi-dimensional analysis of >1,800 genome sequences from clinical L. monocytogenes isolates collected in Germany between 2018-2021. These isolates covered 62% of all notified cases and belonged to 188 infection clusters. 42% of these clusters were active for >12 months, 60% generated cases cross-regionally, including 11 multinational clusters. 37% of the clusters were caused by sequence type (ST) ST6, ST8 and ST1 clones and for selected clusters, we provide further epidemiological and genetic information. Frequencies of materno-fetal and brain infections allowed risk profiling of the most abundant STs, differentiating ST1 as hyper- and ST8, ST14, ST29 as well as ST155 as hypovirulent from ST6 with average virulence potential. Hepatocyte infection experiments confirmed these virulence differences. Inactivating mutations were found in several virulence and house-keeping genes, particularly in hypovirulent STs. Our work supports prioritization of clusters for epidemiological investigations and reinforces the need to analyse the mechanisms underlying hyper- and hypovirulence.

microbiology↗

bioRxiv2024

Multisystemic inflammatory disease in Pheasantshell (Unionidae, Actinonaias pectorosa) associated with Yokenella regensburgei infection at sites experiencing seasonal mass mortality events

Freshwater mussels are integral components of riverine ecosystems, influencing water quality, nutrient cycling, and habitat characteristics. Enigmatic freshwater mussel declines, often characterized by sudden mass mortality events, pose significant challenges to conservation efforts. The Clinch River, a freshwater biodiversity hotspot, has experienced several enigmatic mass mortality events since 2016. Studies have reported bacteria associated with moribund Pheasantshell (Actinonaias pectorosa) during mortality events in the Clinch River, specifically Yokenella regensburgei. Despite reports of bacterial infection, little is known about their role as pathogens. Through a multiyear case-control study, combining in-situ experiments, field surveys, histology, bacterial isolation, and high-throughput sequencing, we assessed the role of bacteria in Pheasantshell (Actinonais pectorosa) mortality at two sites in the Clinch River. Between May 2021 and December 2023, we collected 29 wild moribund free-living A. pectorosa and 68 hatchery-reared A. pectorosa maintained in silos at the same sites and investigated differences in pathology and microbiology between groups. No silo mussels presented clinical signs of disease, or gross or microscopic lesions associated with pathological conditions leading to mortality. Our findings reveal a significant association between Yokenella regensburgei and severe multisystemic and multifocal infiltrative hemocytosis with necrosis, consistent with sepsis. Lesions associated with yokenellosis were of sufficient severity and physiological significance to explain mortality in infected hosts. Although our study does not explain the cause of these infections, it confirms that mussels at our study sites are ultimately dying from an infectious disease and that Y. regensburgei can be pathogenic in free-living mussels. Our results underscore the importance of considering bacterial diseases in wild mussel populations and emphasize the need for further research to elucidate the epidemiology and pathogenicity of Y. regensburgei. Overall, our study highlights the importance of integrated approaches combining pathology, microbiology, and epidemiology in freshwater mussel conservation efforts.

ecology↗

bioRxiv2024

Geographical distribution, disease association and diversity of Klebsiella pneumoniae KL and O antigens in India: roadmap for vaccine development

Klebsiella pneumoniae poses a significant healthcare challenge due to its multidrug resistance and diverse serotype landscape. This study aimed to explore the serotype diversity of 1072 K. pneumoniae and its association with geographical distribution, disease severity and antimicrobial/virulence patterns in India. Whole-genome sequencing was performed on the Illumina platform, and genomic analysis was carried out using the Kleborate tool. KL64 (n=264/1072, 26%), KL51 (249/1072, 24%), KL2 (n=88/1072, 8%), O1/O2v1 (n=471/1072, 44%), O1/O2v2 (n=353/1072, 33%), and OL101 (n=66/1072, 6%) were the most prevalent serotypes. The study identified 119 different sequence types (STs) with varying serotypes, with KL64 being the most predominant in ST231 (26%). O serotypes were strongly linked with STs, with O1/O2v1 predominantly associated with ST231 (44%). Simpsons diversity index and Fishers exact test revealed higher serotype diversity in the north and east regions, along with intriguing associations between specific serotypes and resistance profiles. No significant association between KL or O types and disease severity was observed. Furthermore, we found no specific association of virulence factors with KL types or O antigen types (P>0.05). Conventionally described hypervirulent clones (i.e., KL1 and KL2) in India lacked typical virulent markers (i.e., aerobactin), contrasting with other regional serotypes. The cumulative distribution of KL and O serotypes suggests that future vaccines may have to include either [~]20 KL types or 4 O types to cover >85% of the carbapenemase-producing Indian K. pneumoniae population. The findings underscore the need for a vaccine with broad coverage to address the diverse landscape of K. pneumoniae strains in different regions of India. Understanding regional serotype dynamics is pivotal for targeted surveillance, interventions, and tailored vaccine strategies to tackle the diverse landscape of K. pneumoniae infections across India. Data SummaryO_LIAll the sequenced data has been submitted to the European Nucleotide Archive (ENA) under the Bioproject numbers PRJEB29740 and PRJEB50614. Run Accessions and Biosample numbers are provided in Supplementary Table 1 with corresponding metadata for each sample used in the study. C_LIO_LIThe Microreact link for the genomic analysis is provided (https://microreact.org/project/oqKM84GBszEPW9Emt2FKnP-klebsiella-pneumoniae-indian-serotypes). C_LIO_LIThe pipelines used in the study are published in gitlab (https://gitlab.com/cgps/ghru/pipelines). C_LIO_LIThe tools details and the implementation of the pipelines are described in protocols.io (https://www.protocols.io/view/ghru-genomic-surveillance-of-antimicrobial-resista-bp2l6b11kgqe/v4). C_LIO_LIThe R scripts used with all the input files used for each script have been published in Fishare (https://doi.org/10.6084/m9.figshare.25414807.v1) C_LI Impact StatementKlebsiella pneumoniae produces polysaccharide capsules, which serve as both epidemiological markers and significant virulence factors. The increasing accessibility of whole genome sequencing has made it easier than ever to investigate this capsule diversity. This study is the first of its kind in India to comprehensively investigate the serotype diversity of K. pneumoniae strains and their association with disease severity, antimicrobial resistance/virulence patterns, and geographical distribution across various regions of the subcontinent. This multi-dimensional analysis not only provides valuable insights into the molecular epidemiology of K. pneumoniae in India but also offers crucial data for the development of targeted interventions, including vaccine formulations tailored to address the prevailing serotypes. These findings serve as a foundation for informed decision-making in the management and prevention of K. pneumoniae infections, ultimately contributing to improved public health outcomes in the region.

genomics↗

bioRxiv2024

Development and Validation of Genome-Informed and Multigene-based qPCR and LAMP Assays for Accurate Detection of Dickeya solani: A Critical Quarantine Pathogen Threatening Potato Industry

Dickeya solani, one of the most aggressive pectinolytic phytopathogens, causes blackleg disease in potatoes, resulting in significant economic losses and adversely impacting one of the worlds most important food crops. The diagnostics methods are critical in monitoring the latent infection for international trade of potato seed-tubers and in implementation of control strategies. Our study employed a whole-genome comparative approach, identifying unique target gene loci (LysR and TetR family of transcriptional regulators gene regions), design loop-mediated isothermal amplification (LAMP) and a multi-gene-based multiplex TaqMan qPCR assays for specific detection and differentiation of D. solani. Both methods underwent meticulous validation with extensive inclusivity and exclusivity panels, exhibiting 100% accuracy and no false positives or negatives. The LAMP method demonstrated the detection limit of 100 fg and 1 CFU per reaction using pure genomic DNA and crude bacterial cell lysate, respectively. The qPCR detection limit was 1 pg, 100 fg and 10 fg with Quadplex, triplex and singleplex, respectively. None of the assay showed any inhibitory effect after adding host DNA (in qPCR) or crude lysate (in LAMP). The assays proved robust and reproducible in detecting the target pathogen in infected samples, with the LAMP assay being field-deployable due to its simplicity and rapid results acquisition within approximately 8.92 minutes. The reproducibility was confirmed by performing the assay in two independent laboratories. These developed assays offer a robust, rapid, and reliable solution for routine testing, with applications in phytosanitary inspection and epidemiological studies. IMPORTANCEDickeya solani, one of the most aggressive soft rots causing-bacteria and a quarantine pathogen, poses a severe threat to food security by causing substantial economic losses to potato industry. Accurate and timely detection of this bacteria is vital for monitoring latent infections, particularly for international trade of potato seed tubers, and for implementing effective control strategies. In this research we have developed a LAMP and a multi-gene-based multiplex TaqMan qPCR assays for specific detection of D. solani. These assays, characterized by their precision, rapidity, and robustness, are crucial for distinguishing D. solani from related species. Offering unparalleled sensitivity and specificity, these assays are indispensable for phytosanitary inspection and epidemiological monitoring, providing a powerful tool for management of this threatening pathogen.

microbiology↗

bioRxiv2024

Correlated host movements can reshape spatio-temporal disease dynamics: modeling the contributions of space use to transmission risk using movement data

Despite decades of epidemiological theory making relatively simple assumptions about host movements, it is increasingly clear that non-random movements drastically affect disease transmission. To better predict transmission risk, theory needs to simultaneously account for how the environment affects host space use and how social dynamics affect correlation in space use. We develop new theory that decomposes the relative contributions of fine-scale space use and correlated movements to spatio-temporal transmission risk. Using analytical results, simulations, and empirical movement data, we show that even weak correlations can increase transmission risk by orders of magnitude compared to independent movement. Accounting for correlation is especially critical for pathogens with direct transmission or short environmental persistence. Our theory provides clear expectations for what has been observed empirically but largely ignored in disease models--movement correlation can reshape epidemiological landscapes, creating transmission hotspots whose magnitude and location are not necessarily predictable from spatial overlap alone.

ecology↗

bioRxiv2024

A scoping review of evidence of naturally occurring Japanese encephalitis infection in vertebrate animals other than humans, ardeid birds and pigs

Japanese encephalitis virus (JEV) is the leading cause of human encephalitis in Asia. JEV is a vector-borne disease, mainly transmitted by Culex mosquitoes, with Ardeidae birds as maintenance hosts and pigs as amplifying hosts. Other vertebrate animal hosts have been suggested to play a role in the epidemiology of JEV. This scoping review followed PRISMA guidelines to identify species in which evidence of naturally occurring JEV infection was detected in vertebrates other than ardeid birds, pigs and people. Following systematic searches, 4372 records were screened, and data were extracted from 62 eligible studies. Direct evidence (virus, viral antigen or viral RNA) of JEV infection was identified in a variety of mammals and birds (not always identified to the species level), including bats, passerine birds (family Turdidae), livestock (cattle [Bos taurus] and a goat [Capra hircus]), carnivores (two meerkats [Suricata suricatta]), and one horse (Equus caballus). Bat families included Pteropodidae, Vespertilionidae, Rhinolophidae, Miniopteridae, Hipposideridae. Indirect evidence suggestive of JEV infection (antibodies) was detected in several mammalian and avian orders, as well as reported in two reptile species. However, a major limitation of the evidence of JEV infection identified in this review was diagnostic test accuracy, particularly for serological testing. Studies generally did not report diagnostic sensitivity or specificity. Although we hypothesise that bats and passerine birds could play an underappreciated role in JEV epidemiology, development of diagnostic tests to differentiate JEV from other orthoflaviviruses will be critical for effective surveillance in these, as well as the companion and livestock species that could be used to evaluate JEV control measures in currently endemic regions.

ecology↗

bioRxiv2024

Polygenic hazard score models for the prediction of Alzheimer's free survival using the lasso for Cox's proportional hazards model

The prediction of the susceptibility of an individual to a certain disease is an important and timely research area. An established technique is to estimate the risk of an individual with the help of an integrated risk model, that is a polygenic risk score with added epidemiological covariates. However, integrated risk models do not capture any time dependence, and may provide a point estimate of the relative risk with respect to a reference population. The aim of this work is twofold. First, we explore and advocate the idea of predicting the time dependent hazard and survival (defined as disease free time) of an individual for the onset of a disease. This provides a practitioner with a much more differentiated view of the absolute survival as a function of time. Second, to compute the time dependent risk of an individual, we use published methodology to fit a Coxs proportional hazard model to data from a genetic SNP study of time to Alzheimers disease (AD) onset, using the lasso to incorporate further epidemiological variables such as sex, APOE (apolipoprotein E, a genetic risk factor for AD) status, ten leading principal components, and selected genomic loci. We apply the lasso for Coxs proportional hazards to a dataset of 6792 AD patients (composed of 4102 cases and 2690 controls) and 87 covariates. We demonstrate that fitting a lasso model for Coxs proportional hazards allows one to obtain more accurate survival curves than with state-of-the-art (likelihood-based) methods. Moreover, the methodology allows one to obtain personalized survival curves for a patient, thus giving a much more differentiated view of the expected progression of a disease than the view offered by integrated risk models. The runtime to compute personalized survival curves is under a minute for the entire dataset of AD patients, thus enabling it to handle datasets with 60, 000 to 100, 000 subjects in less than one hour.

bioinformatics↗

bioRxiv2024

A comparative analysis of Parkinson's disease and inflammatory bowel disease gut microbiomes highlights shared depletions in key butyrate-producing bacteria

Epidemiological studies reveal that a diagnosis of inflammatory bowel disease (IBD) is associated with an increased risk of developing Parkinsons disease (PD). The presence of gut dysbiosis has been documented in both PD and IBD patients, however it is currently unknown how alterations in the gut microbiome may contribute to the epidemiological link between both diseases. To identify shared and distinct features of the PD and IBD microbiome, we performed the first joint analysis of 54 PD, 26 IBD, and 16 healthy control gut metagenomes recruited from clinics at the University of Florida, and directly compared the gut microbiomes from PD and IBD persons. Larger, publicly available PD and IBD metagenomic datasets were also analyzed to validate and extend our findings. Depletions in short-chain fatty acid (SCFA) producing bacteria, including Roseburia intestinalis, Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium rectale, as well as depletions in SCFA synthesis pathways, were demonstrated across PD and IBD datasets. We posit that direct comparison of PD and IBD gut microbiomes will be important in identifying features within the IBD gut which may be associated with PD. The data revealed a consistent depletion in SCFA-producing bacteria across both PD and IBD, suggesting that loss of these microbes may influence the pathophysiology of both disease states.

neuroscience↗

bioRxiv2024

New insights into the echinocandin resistance in Candida spp. in the clinical setting

Despite a huge consumption of echinocandins, the emergence of resistance in Candida spp has remained overall limited. Here, we depicted the epidemiology of Candida spp in our center face to the echinocandins consumption. We postulate new hypotheses that may explain the shaping of candines resistance in the clinical setting. Epidemiology of Candida infections and echinocandin consumption were evaluated in our center over 12 years (2006-2018). Glucan synthase genes (fks1, fks2) were sequenced. The in vitro fitness was assessed for couple of isogenic strains, of which one was resistant. Finally, the modelling of Candida FKS proteins was realized. Despite a three-fold increase in echinocandin consumption, no significant emergence of resistance was observed. In Candida albicans, fks1 mutations affect the three-dimensional conformation of the glucan synthase, which may result in altered export of the glucan chain, which could explain the observed reduced fitness. In contrast, cross-complementation between FKS1 and FKS2 in Nakaseomyces glabratus might circumvent the negative impact on fitness. ConclusionsOur results support the fact that N. glabratus is more prone to the spread of echinocandin-resistant strains. The link between mutations in the glucan synthase and fitness of Candida strains might explain the difference in the species-specific emergence of echinocandins-resistant strains.

microbiology↗

bioRxiv2024

Basic reproduction number for pandemic Escherichia coli clones is comparable to typical pandemic viruses

Extra-intestinal pathogenic Escherichia coli (ExPEC) ubiquitously colonize the human gut and represent clinically the most significant bacterial species causing urinary tract infections and bacteremia in addition to contributing to meningitis in neonates. During the last two decades, new E. coli multi-drug resistant clones such as ST131, particularly its clades C1 and C2, have spread globally, as has their generally less resistant sister clade ST131-A. Phylodynamic coalescent modeling has indicated exponential growth in the populations corresponding to these clades during the early 2000s. However, it remains unknown how their transmission dynamics compare to viral epidemics and pandemics in terms of key epidemiological quantities such as the basic reproduction number (R0). Estimation of R0 for opportunistic pathogenic bacteria poses a difficult challenge compared to viruses causing acute infections, since data on E. coli infections accumulate with a much longer delay, even in the most advanced public health reporting systems. Here, we developed a compartmental model for asymptomatic gut colonization and onward transmission coupled with a stochastic epidemiological observation model for bacteremia and fitted the model to annual Norwegian national E. coli disease surveillance and bacterial population genomics data. Approximate Bayesian Computation leveraged by the ELFI software package was used to infer R0 for the pandemic ST131 clades. The resulting R0 estimates for ST131-A, ST131-C1 and ST131-C2 were 1.47 (1.31-1.60), 1.18 (1.12-1.20) and 1.13 (1.08-1.20), respectively, indicating that the ST131-A transmission potential can be even comparable to pandemic influenza viruses, such as H1N1. The significantly lower transmissibility of ST131-C1 and ST131-C2 suggests that their global dissemination has been aided by antibiotic selection pressure and that they may be more effectively transmitted through healthcare facilities instead of primarily community-driven transmission. In summary our results provide a fundamental advance in understanding the relative transmissibility of these opportunistic pathogens and that it can vary markedly even between very closely related E. coli.

microbiology↗

bioRxiv2024

Phylogenetic-based methods for fine-scale classification of PRRSV-2 ORF5 sequences: a comparison of their robustness and reproducibility

Disease management and epidemiological investigations of porcine reproductive and respiratory syndrome virus-type 2 (PRRSV-2) often rely on grouping together highly related sequences. In the USA, the last five years have seen a major paradigm shift within the swine industry when classifying PRRSV-2, beginning to move away from RFLP (restriction fragment length polymorphisms)-typing and adopting the use of phylogenetic lineage-based classification. However, lineages and sub-lineages are large and genetically diverse, and the rapid mutation rate of PRRSV coupled with the global prevalence of the disease has made it challenging to identify new and emerging variants. Thus, within the lineage system, a dynamic fine-scale classification scheme is needed to provide better resolution on the relatedness of PRRSV-2 viruses to inform disease management and monitoring efforts and facilitate research and communication surrounding circulating PRRSV viruses. Here, we compare potential fine-scale systems for classifying PRRSV-2 variants (i.e., genetic clusters of closely related ORF5 sequences at finer scales than sub-lineage) using a database of 28,730 sequences from 2010 to 2021, representing >55% of the U.S. pig population. In total, we compared 140 approaches that differed in their tree-building method, criteria, and thresholds for defining variants within phylogenetic trees using TreeCluster. Three approaches produced epidemiologically meaningful variants (i.e., [≥]5 sequences per cluster), and resulted in reproducible and robust outputs even when the input data or input phylogenies were changed. In the three best performing approaches, the average genetic distance amongst sequences belonging to the same variant was 2.1 - 2.5%, and the genetic divergence between variants was 2.5-2.7%. Machine learning classification algorithms were also trained to assign new sequences to an existing variant with >95% accuracy, which shows that newly generated sequences could be assigned without repeating the phylogenetic and clustering analyses. Finally, we identified 73 sequence-clusters (dated <1 year apart with close phylogenetic relatedness) associated with circulation events on single farms. The percent of farm sequence-clusters with an ID change was 6.5-8.7% for our best approaches. In contrast, [~]43% of farm sequence-clusters had variation in their RFLP-type, further demonstrating how our proposed fine-scale classification system addresses shortcomings of RFLP-typing. Through identifying robust and reproducible classification approaches for PRRSV-2, this work lays the foundation for a fine-scale system that would more reliably group related field viruses and provide better improved clarity for decision-making surrounding disease management.

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