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bioRxiv2020

Assessing the co-variability of DNA methylation across peripheral cells and tissues: implications for the interpretation of findings in epigenetic epidemiology

Summary/AbstractO_ST_ABSBackgroundC_ST_ABSMost epigenome-wide association studies (EWAS) quantify DNA methylation (DNAm) in peripheral tissues such as whole blood to identify positions in the genome where variation is statistically associated with a trait or exposure. As whole blood comprises a mix of cell types, it is unclear whether trait-associated variation is specific to an individual cellular population. MethodsWe collected three peripheral tissues (whole blood, buccal and nasal epithelial cells) from thirty individuals. Whole blood samples were subsequently processed using fluorescence-activated cell sorting (FACS) to purify five constituent cell-types (monocytes, granulocytes, CD4+ T cells, CD8+ T cells, and B cells). DNAm was profiled in all eight sample-types from each individual using the Illumina EPIC array. ResultsWe identified significant differences in both the level and variability of DNAm between different tissues and cell types, and DNAm data-derived estimates of age and smoking were found to differ dramatically across sample types from the same individual. We found that for the majority of loci variation in DNAm in individual blood cell types was only weakly predictive of variance in DNAm measured in whole blood, however, the proportion of variance explained was greater than that explained by either buccal or nasal tissues. Instead we observe that DNAm variation in whole blood is additively influenced by a combination of the major blood cell types. For a subset of sites variable DNAm detected in whole blood can be attributed to variation in a single blood cell type providing potential mechanistic insight. ConclusionsWe identified major differences in DNAm between blood cell types and peripheral tissues, with each sample type being characterized by a unique DNAm signature across multiple loci. Our results suggest that associations between whole blood DNAm and traits or exposures reflect differences in multiple cell types and provide important insights for the interpretation of EWAS performed in whole blood. Key MessagesO_LIWe identified major differences in DNA methylation between blood cell types and peripheral tissues, with each sample type being characterized by a unique DNA methylation signature across multiple loci. C_LIO_LIEstimates of DNAmAge and tobacco smoking from DNA methylation data can be highly variable across different sample types collected from the same individual at the same time. C_LIO_LIWhile individual blood cell types did predict more of the variation in whole blood compared to buccal epithelial and nasal epithelial cells, the percentage of variance explained was still small. C_LIO_LIInstead our data indicate that at the majority of sites, variation in multiple blood cell types additively combines to drive variation in DNA methylation in whole blood. C_LIO_LIThere are subset of sites where variable DNA methylation detected in whole blood can be attributed to variation in a single blood cell type. C_LI

genomics↗

bioRxiv2020

AGE IS ASSOCIATED WITH INCREASED EXPRESSION OF PATTERN RECOGNITION RECEPTOR GENES AND ACE2, THE RECEPTOR FOR SARS-COV-2: IMPLICATIONS FOR THE EPIDEMIOLOGY OF COVID-19 DISEASE

Older aged adults and those with pre-existing conditions are at highest risk for severe COVID-19 associated outcomes. Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts (GSE113957) we investigated whether age affects the expression of pattern recognition receptor (PRR) genes and ACE2, the receptor for SARS-CoV-2. Older age was associated with increased expression of PRR genes, ACE2 and four genes that encode proteins that have been shown to interact with SAR2-CoV-2 proteins. Assessment of PRR expression might provide a strategy for stratifying the risk of severe COVID-19 disease at both the individual and population levels.

molecular biology↗

bioRxiv2020

Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches

Whole Genome Sequence of four samples from COVID-19 outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, England). The constructed phylogenetic tree indicates probable multiple independent introduction events. The success of future containment measures concernig new introductions will be highly challenging for country due to the significant proportion of BH population living abroad.

genetics↗

bioRxiv2020

Genomic variations in SARS-CoV-2 genomes from Gujarat: Underlying role of variants in disease epidemiology

Humanity has seen numerous pandemics during its course of evolution. The list includes many such as measles, Ebola, SARS, MERS, etc. Latest edition to this pandemic list is COVID-19, caused by the novel coronavirus, SARS-CoV-2. As of 4th July 2020, COVID-19 has affected over 10 million people from 170+ countries, and 5,28,364 deaths. Genomic technologies have enabled us to understand the genomic constitution of the pathogens, their virulence, evolution, rate of mutations, etc. To date, more than 60,000 virus genomes have been deposited in the public depositories like GISAID and NCBI. While we are writing this, India is the 3rd most-affected country with COVID-19 with 0.6 million cases, and >18000 deaths. Gujarat is the fourth highest affected state with 5.44 percent death rate compared to national average of 2.8 percent. Here, 361 SARS-CoV-2 genomes from across Gujarat have been sequenced and analyzed in order to understand its phylogenetic distribution and variants against global and national sequences. Further, variants were analyzed from diseased and recovered patients from Gujarat and the World to understand its role in pathogenesis. From missense mutations, found from Gujarat SARS-CoV-2 genomes, C28854T, deleterious mutation in nucleocapsid (N) gene was found to be significantly associated with mortality in patients. The other significant deleterious variant found in diseased patients from Gujarat and the world is G25563T, which is located in Orf3a and has a potential role in viral pathogenesis. SARS-CoV-2 genomes from Gujarat are forming distinct cluster under GH clade of GISAID.

genomics↗

bioRxiv2020

Ecology and Epidemiology of Wheat Curl Mite and Mite-Transmissible Viruses in Colorado and Insights into the Wheat Virome

The wheat curl mite (WCM)-transmissible wheat streak disease complex is the most serious disease of wheat in the U.S. Great Plains. In the current study, we determined the genetic variability in WCM and mite-transmitted viruses in Colorado and identified sources of resistance in Colorado wheat germplasm to wheat streak disease complex. We identified two distinct genotypes of WCM, Type 1 and Type 2 based on the ribosomal ITS1 region. Both genotypes were found to co-exist throughout the wheat producing regions of Colorado. Analysis of the whole genome and partial coat protein sequences revealed rich diversity of wheat streak mosaic virus (WSMV) and High Plains wheat mosaic virus (HPWMoV) isolates collected from Colorado, whereas triticum mosaic virus (TriMV) showed low sequence variability. Analysis of WSMV isolates revealed two novel isolates and one that was 100% similar to a new variant of WSMV from Kansas. Interestingly, between 2-4 genotypes of all 8 RNA segments of HPWMoV were identified, which suggests new variants of emaraviruses and co-occurrence of multiple strains within host populations. Several novel viruses including mycoviruses were identified for the first time in Colorado. We found variation in WSMV resistance among wheat varieties; however a variety that harbored dual resistance to mite and WSMV had lower virus titer compared to varieties that contained single resistance gene. This suggests that pyramiding genes will ensure improved and durable resistance. Future research may be aimed at elucidating the dynamics, diversity, and distribution of the new WSMV and HPWMoV isolates and their responses to wheat genotypes.

pathology↗

bioRxiv2020

Deciphering the genetic and epidemiological landscape of mitochondrial DNA abundance

Somatically acquired whole chromosome loss in nucleated blood cells is an indicator of immune aging and genomic instability. However, little is known about aging, lifestyle and genetic factors influencing mitochondrial (MT) DNA abundance. In this study, MT DNA abundance was estimated from the weighted intensities of probes mapping to the MT genome in 295,150 participants from the UK Biobank. We found that abundance of MT DNA was significantly elevated in women compared to men, was negatively correlated with advanced age, more packyears, greater body-mass index, higher frailty index as well as elevated red and white blood cell count and, importantly, lower mortality. In addition, several biochemistry markers in blood related to cholesterol metabolism, ion homeostasis and kidney function were found to be significantly associated with MT DNA abundance. By performing a genome-wide association study, we identified 50 independent regions genome-wide significantly associated with MT DNA abundance which harbour multiple genes involved in the immune system, cancer as well as mitochondrial function. Using mixed effects models, we estimated the SNP-heritability of MT DNA abundance to be around 8%. To investigate the consequence of altered MT DNA abundance, we performed a phenome-wide association study and found that MT DNA abundance is involved in risk for leukaemia, hematologic diseases as well as hypertension. Thus, estimating MT DNA abundance from genotyping arrays has the potential to provide novel insights into age- and disease relevant processes, particularly those related to immunity and established mitochondrial functions.

genomics↗

bioRxiv2021

Molecular epidemiology of human respiratory syncytial virus with severe acute respiratory infection in Huzhou from 2016 to 2019

BackgroundHuman respiratory syncytial virus (HRSV) is one of the major cause of acute lower respiratory infection in infants, the elderly and people with low immunity worldwide. Based on antigenic and genetic variations, Human respiratory syncytial virus is divided into two subgroups (A and B). Each of the subgroups is further categorized into genotypes based on the phylogenetic analyses of the sequences of the second hypervariable region. MethodsNasopharyngeal swabs (NPSs) were collected from patients of the First Peoples Hospital in Huzhou from January 2016 to December 2019. Real-time RT-PCR (qPCR) was performed using double nucleic acid detection kit for respiratory syncytial virus (A\B) (Shenzhen shengkeyuan) with the ABI Q7 (Applied Biosystems). For genotyping, the primer set A-F/A-R was used to amplify the G protein of HRSV-A. Primer set B-F/B-R was used to amplify the G protein of HRSV-B. The phylogenetic analysis was constructed using the neighbor-joining algorithm with the Kimura two-parameter model and supported statistically by bootstrapping with 1000 replicates with MEGA software (version 7.0) with 1000 bootstrap replicates. ResultsA total of 973 nasopharyngeal swab samples were collected from January 2016 to December 2019, and 63 samples were positive for RSV nucleic acid, with the detection rate of 6.47%. Of the positive specimens, 28 were belonged to HRSV-A, and 35 were belonged to HRSV-B. Infection with RSV was found in all age groups tested, with the 0-1 year age group having the highest detection rate 15.2%. The detection rate was high from November to next March. Phylogenetic analysis clustered HRSV-A strains identified in Huzhou into ON1genotype. All 17 of the HRSV-B strains belonged to BA9 genotype. ConclusionsWe analyzed the HRSV strains circulation in Huzhou from January 2016 to December 2019 in Huzhou, China. This is the first molecular analysis on HRSV in Huzhou. We found Subgroup A and B of RSV were co-circulating and the 0-1 year age group having the highest infection rate.

molecular biology↗

bioRxiv2021

From partial to whole genome imputation of SARS-CoV-2 for epidemiological surveillance

Backgroundthe current SARS-CoV-2 pandemic has emphasized the utility of viral whole genome sequencing in the surveillance and control of the pathogen. An unprecedented ongoing global initiative is increasingly producing hundreds of thousands of sequences worldwide. However, the complex circumstances in which viruses are sequenced, along with the demand of urgent results, causes a high rate of incomplete and therefore useless, sequences. However, viral sequences evolve in the context of a complex phylogeny and therefore different positions along the genome are in linkage disequilibrium. Therefore, an imputation method would be able to predict missing positions from the available sequencing data. ResultsWe developed impuSARS, an application that includes Minimac, the most widely used strategy for genomic data imputation and, taking advantage of the enormous amount of SARS-CoV-2 whole genome sequences available, a reference panel containing 239,301 sequences was built. The impuSARS application was tested in a wide range of conditions (continuous fragments, amplicons or sparse individual positions missing) showing great fidelity when reconstructing the original sequences. The impuSARS application is also able to impute whole genomes from commercial kits covering less than 20% of the genome or only from the Spike protein with a precision of 0.96. It also recovers the lineage with a 100% precision for almost all the lineages, even in very poorly covered genomes (< 20%) Conclusionsimputation can improve the pace of SARS-CoV-2 sequencing production by recovering many incomplete or low-quality sequences that would be otherwise discarded. impuSARS can be incorporated in any primary data processing pipeline for SARS-CoV-2 whole genome sequencing.

genomics↗

bioRxiv2021

Phylogenomic analysis of Uganda influenza type-A viruses to assess their relatedness to the vaccine strains and other Africa viruses: a molecular epidemiology study.

BackgroundGenetic characterisation of circulating influenza viruses is essential for vaccine selection and mitigation of viral transmission. The current scantiness of viral genomic data and underutilisation of advanced molecular analysis methods on influenza viruses circulating in Africa has limited their extensive study and representation in the global influenza ecology. We aimed to sequence influenza type-A viruses (IAVs) that previously circulated in Uganda and characterised their genetic relatedness to the vaccine viruses and publicly available Africa IAVs. MethodsThis was an observational study nested to the Uganda national influenza surveillance programme. We used Next-generation sequencing to locally generate genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) viruses collected between 2010 and 2018 from 7 districts across Uganda. A total of 206 hemagglutinin (HA), 207 neuraminidase (NA), and 213 matrix protein (MP) sequences were genetically compared to the WHO-recommended vaccines and other viruses isolated from Africa since 1994. Viral temporal and spatial divergence and circulating genetic clades were characterised using phylogenetic methods. FindingsWe successfully generated gene sequences for 91{middle dot}9% (215/234) viruses. Uganda A(H1N1)pdm09 and A(H3N2) virus HA, NA, and MP proteins had 96{middle dot}36-99{middle dot}09%, 96{middle dot}49-99{middle dot}39%, and 97{middle dot}48-99{middle dot}95% amino acid similarity, respectively, to vaccines recommended from 2010 through 2020. The local viruses incorporated amino acid substitutions (AAS) in their antigenic, receptor binding, and glycosylation sites each year causing them to antigenically drift away from vaccines. For seasons when vaccine formulations differed, Uganda IAV antigenic sites had 1-2 extra AAS relative to the Southern than Northern hemisphere vaccine viruses. All Uganda IAVs carried the adamantine-resistance marker S31N but not the neuraminidase inhibitor (NAI) resistance markers H274Y and H275Y. However, some A(H1N1)pdm09 viruses had permissive substitutions V234I, N369K, and V241I typical of NAI-resistant viruses. The 2017-2018 A(H1N1)pdm09 viruses belonged to global genetic clade 6B.1, while the A(H3N2) viruses isolated in 2017 belonged to clades 3C.2a and 3C.3a. Uganda IAVs obtained before 2016 clustered distinctly from other Africa viruses while later viruses mixed with other Africa, especially Kenya and Congo, and global viruses. Several unique viral lineages (bootstrap >90) persisted in Uganda and other countries for 1-3 years. InterpretationThe study reveals Uganda as part of the global influenza ecology with continuous importation, antigenic drift, and extensive local transmission of IAVs, presenting a potential risk of future outbreaks. For a country with limited health resources and where social distancing is not sustainable, viral prevention by vaccination should be prioritized. The notable viral diversity in Africa is a warning to countries to broaden and incorporate genome analysis in routine surveillance to monitor circulating and detect new viruses. This knowledge can inform virus selection for vaccine production and assist in developing cost-effective virus control strategies. FundingThis work was supported by the Makerere University-Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII). MUII is supported through the Developing Excellence in Leadership, Training and Science (DELTAS) Africa Initiative (Grant no. 107743). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA), and supported by the New Partnership for Africas Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (Grant no. 107743) and the UK Government. The work was also funded in part by a Wellcome Trust grant (102975).

evolutionary biology↗

bioRxiv2021

Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats

In the largest DNA-based study of domestic cat to date, 11,036 individuals (10,419 pedigreed cats from 91 breeds and breed types and 617 non-pedigreed cats) were genotyped via commercial panel testing, elucidating the distribution and frequency of known genetic variants associated with blood type, disease and physical traits across cat breeds. Blood group determining variants, which are relevant clinically and in cat breeding, were genotyped to assess the across breed distribution of blood types A, B and AB. Extensive panel testing identified 13 disease-associated variants in 48 breeds or breed types for which the variant had not previously been observed, strengthening the argument for panel testing across populations. The study also indicates that multiple breed clubs have effectively used DNA testing to reduce disease-associated genetic variants within certain pedigreed cat populations. Appearance-associated genetic variation in all cats is also discussed. Additionally, we combined genotypic data with phenotype information and clinical documentation, actively conducted owner and veterinarian interviews, and recruited cats for clinical examination to investigate the causality of a number of tested variants across different breed backgrounds. Lastly, genome-wide informative SNP heterozygosity levels were calculated to obtain a comparable measure of the genetic diversity in different cat breeds. This study represents the first comprehensive exploration of informative Mendelian variants in felines by screening over 10,000 domestic cats. The results qualitatively contribute to the understanding of feline variant heritage and genetic diversity and demonstrate the clinical utility and importance of such information in supporting breeding programs and the research community. The work also highlights the crucial commitment of pedigreed cat breeders and registries in supporting the establishment of large genomic databases that when combined with phenotype information can advance scientific understanding and provide insights that can be applied to improve the health and welfare of cats.

genetics↗

bioRxiv2021

Epidemiological and ecological consequences of virus manipulation of host and vector in plant virus transmission

Many plant viruses are transmitted by insect vectors. Transmission can be described as persistent or non-persistent depending on rates of acquisition, retention, and inoculation of virus. Much experimental evidence has accumulated indicating vectors can prefer to settle and/or feed on infected versus noninfected host plants. For persistent transmission, vector preference can also be conditional, depending on the vectors own infection status. Since viruses can alter host plant quality as a resource for feeding, infection potentially also affects vector population dynamics. Here we use mathematical modelling to develop a theoretical framework addressing the effects of vector preferences for landing, settling and feeding - as well as potential effects of infection on vector population density - on plant virus epidemics. We explore the consequences of preferences that depend on the host (infected or healthy) and vector (viruliferous or nonviruliferous) phenotypes, and how this is affected by the form of transmission, persistent or non-persistent. We show how different components of vector preference have characteristic effects on both the basic reproduction number and the final incidence of disease. We also show how vector preference can induce bistability, in which the virus is able to persist even when it cannot invade from very low densities. Feedbacks between plant infection status, vector population dynamics and virus transmission potentially lead to very complex dynamics, including sustained oscillations. Our work is supported by an interactive interface https://plantdiseasevectorpreference.herokuapp.com/. Our model reiterates the importance of coupling virus infection to vector behaviour, life history and population dynamics to fully understand plant virus epidemics. AUTHOR SUMMARYPlant virus diseases - which cause devastating epidemics in plant populations worldwide - are most often transmitted by insect vectors. Recent experimental evidence indicates how vectors do not choose between plants at random, but instead can be affected by whether plants are infected (or not). Virus infection can cause plants to "smell" different, because they produce different combinations of volatile chemicals, or "taste" different, due to chemical changes in infected tissues. Vector reproduction rates can also be affected when colonising infected versus uninfected plants. Potential effects on epidemic spread through a population of plants are not yet entirely understood. There are also interactions with the mode of virus transmission. Some viruses can be transmitted after only a brief probe by a vector, whereas others are only picked up after an extended feed on an infected plant. Furthermore there are differences in how long vectors remain able to transmit the virus. This ranges from a matter of minutes, right up to the entire lifetime of the insect, depending on the plant-virus-vector combination under consideration. Here we use mathematical modelling to synthesise all this complexity into a coherent theoretical framework. We illustrate our model via an online interface https://plantdiseasevectorpreference.herokuapp.com/.

ecology↗

bioRxiv2021

Evolutionary epidemiology of a zoonosis

Cryptosporidium parvum is a global zoonoses and a major cause of diarrhoea in humans and ruminants. The parasites life cycle comprises an obligatory sexual phase, during which genetic exchanges can occur between previously isolated lineages. Here, we compare 32 whole genome sequences from human- and ruminant-derived parasite isolates collected across Europe, Egypt and China. We identify three strongly supported clusters that comprise a mix of isolates from different host species, geographic origins, and subtypes. We show that: (1) recombination occurs between ruminant isolates into human isolates; (2) these recombinant regions can be passed on to other human subtypes through gene flow and population admixture; (3) there have been multiple genetic exchanges, and all are likely recent; (4) putative virulence genes are significantly enriched within these genetic exchanges, and (5) this results in an increase in their nucleotide diversity. We carefully dissect the phylogenetic sequence of two genetic exchanges, illustrating the long-term evolutionary consequences of these events. Our results suggest that increased globalisation and close human-animal contacts increase the opportunity for genetic exchanges between previously isolated parasite lineages, resulting in spillover and spillback events. We discuss how this can provide a novel substrate for natural selection at genes involved in host-parasite interactions, thereby potentially altering the dynamic coevolutionary equilibrium in the Red Queens arms race. Data SummaryAll raw and processed sequencing data generated and analysed during the current study have been submitted to the NCBI Sequence Read Archive (https://www.ncbi.nlm.nih.gov/bioproject/), under BioProjects PRJNA634014 and PRJNA633764.

evolutionary biology↗

bioRxiv2021

The epidemiology and genomics of a virulent emerging fungal pathogen in an Australian reptile

Emerging infectious fungal diseases (EIFDs) represent a major conservation concern worldwide. Here, we provide early insights into the potential threat that Nannizziopsis barbatae (Nb), a novel EIFD, poses to Australian herpetological biodiversity. First known to the reptile pet trade as a primary pathogen causing untreatable severe dermatomycosis, since 2013, Nb has emerged in a growing number of phylogenetically and ecologically distant free-living reptiles across Australia. Observing its emergence in a long-term study population of wild eastern water dragons (Intellagama lesueurii), we demonstrate the pathogens virulence-related genomic features, within-population spatiotemporal spread, and survival costs, all of which imply that Nb could pose a threat to Australian reptiles in the future. Our findings highlight the need to closely monitor this pathogen in Australian ecosystems.

ecology↗

bioRxiv2022

Genetic epidemiology of human neutrophil antigen variants suggest significant global variability

Human neutrophil antigens possess significant clinical implications especially in the fields of transfusion and transplantation medicine. Efforts to estimate the prevalence of genetic variations underpinning the antigenic expression are emerging. However, there lacks a precise capture of the global frequency profiles. Our article emphasizes the potential utility of maintaining an organized online repository of evidence on neutrophil antigen associated genetic variants from published literature and reports. This in our opinion, is an emerging area and would significantly benefit from the awareness and understanding of population-level diversities.

genomics↗

bioRxiv2022

Molecular epidemiology of carbapenemase-producing Acinetobacter spp. from Israel, 2001-2006: earliest report of blaNDM predating the oldest known blaNDM-positive strains

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAb) is a WHO priority 1 critical pathogen. Despite early emergence of elevated CRAb rates in Israel, limited molecular data from this location are available. We searched for carbapenemases among 198 clinical Acinetobacter spp. from Israel between 2001 and 2006. MethodsStrains from 3 archives underwent whole-genome sequencing (Illumina NovaSeq on all, MinION on a subset) and computational analyses: assembly (Unicycler), annotation (prokka), identification (Kraken, rpoB similarity), search for carbapenemases (ResFinder, BLDB curation). FindingsA. baumannii (Ab) represented 179 (90{middle dot}4%) Acinetobacter spp. Eighty-four Ab (46{middle dot}9%) carried a carbapenemase: 38 (45{middle dot}2%) blaOXA-72 (blaOXA-24-like); 28 (33{middle dot}3%) blaOXA-23-like (20 blaOXA-23 and 8 blaOXA-225); 18 (21{middle dot}5%) blaOXA-58 (16 from 2001-2). Carbapenemase rates increased yearly from 2002 (32%) to 2006 (67%). Eight species of non-baumannii Acinetobacter (NbA) accounted for 19 isolates (9{middle dot}6%). Two of three A. junii contained blaOXA-58, one of which, Ajun-H1-3, isolated in January 2004, also possessed blaNDM-1. The pNDM-Ajun-H1-3 plasmid matched numerous NDM-positive plasmids reported from 2005 onwards in Acinetobacter spp. as well as Enterobacterales. InterpretationWe assessed carbapenemase diversity among Acinetobacter spp. in Israel from 2001-2006. Findings in Ab predate observations elsewhere: rapidly rising carbapenemase rates, driven by blaOXA-23-like and blaOXA-24-like genes replacing blaOXA-58. Among NbA, an A. junii isolated in 2004 carried blaNDM-1, making it the earliest NDM-positive isolate reported to date, preceding those from 2005 in India. Further research into blaNDMs emergence is warranted, in order to shed light on the evolution and spread of this and other antibiotic-resistance genes. FundingCentre de recherche Charles-Le Moyne; Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Universite de Sherbrooke; Fonds de recherche du Quebec - Sante; New Frontiers in Research Fund Grant NFRFE-2019-00444; CIFAR-Azrieli Global Scholars Program.

microbiology↗

bioRxiv2022

Tolerant crops increase growers' yields but promote selfishness: how the epidemiology of disease resistant and tolerant varieties affect grower behaviour

1O_LIDisease management often involves genetically improved crops. Resistant varieties are less susceptible, and so less likely to act as reservoirs of inoculum. Tolerant varieties can be highly susceptible, but limit yield loss for those who grow them. Population-scale effects of deploying resistant or tolerant varieties have received little consideration from epidemiologists. C_LIO_LIWe examined how tolerant and resistant crop have opposing consequences upon the uptake of control using a behavioural model based on strategic-adaptive expectations. Growers compared last seasons profit with an estimate of what could be expected from the alternative crop type, thereby assessing whether to alter their strategy for the next season. C_LIO_LITolerant crop only benefited growers using it, decreasing yields for others. This incentivises widespread use via a negative feedback loop. Resistant crop was more widely beneficial, with reduced population-scale disease pressure leading to increased yields for all. However, this positive externality allows growers who do not deploy resistant crop to "free-ride" upon the management of others. C_LIO_LIThis work highlights how a community of growers responds to the contrasting incentives caused by tolerant and resistant crop varieties, and how this leads to very distinct effects on yields and population-scale deployment. C_LI

ecology↗

bioRxiv2022

Diversity and characteristics of pTet family plasmids revealed by genomic epidemiology of Campylobacter jejuni from human patients in Toyama, Japan from 2015 to 2019

This study investigated 116 clinical isolates of Campylobacter jejuni from Toyama, Japan, which were isolated from 2015 to 2019. Antimicrobial susceptibility testing and whole-genome sequencing were used for phenotypic and genotypic characterization to compare antimicrobial resistance (AMR) profiles and phylogenic linkage. The multilocus sequence typing approach identified 37 sequence types (STs) and 15 clonal complexes (CCs), including 7 novel STs, and the high frequency CCs were CC21 (27.7%), CC48 (10.9%), and CC354 (9.9%). Overall, 58.6% of the isolates were resistant to at least one of the antibiotics and 3.4% were resistant to three or more antibiotic classes. The AMR profiles and related resistant factors were as follows; fluoroquinolones (51.7%), mutation in QRDRs (GyrA T86I), tetracyclines (27.6%), acquisition of tet(O), ampicillin (5.2%), promoter mutation in blaOXA193, aminoglycosides (1.7%), acquisition of ant(6)-Ia and aph(3)-III, chloramphenicol (0.9%), acquisition of cat. The resistance factors of fosfomycin (1 strain), sulfamethoxazole-trimethoprim (2 strain), and linezolid (1 strain) resistant isolates were unknown. The acquired resistance genes, tet(O), ant(6>)-Ia, aph(3)-III, and cat, were located on pTet family plasmids. Furthermore, three pTet family plasmids formed larger plasmids that incorporated additional genes such as the Type IV secretion system. A comparison of pTet family plasmids in Japan has not been reported, and these results imply that the diversity of pTet family plasmids has increased. The prevalence of ST4526, belonging to CC21, in Japan has been reported, and it was also the major ST type (10.9%) in this study, suggesting that the ST4526 prevalence continues in Japan.

microbiology↗

bioRxiv2022

Coupling machine learning and epidemiological modelling to characterise optimal fungicide doses when fungicide resistance is partial or quantitative

Increasing fungicide dose tends to lead to better short-term control of plant diseases. However, high doses select more rapidly for fungicide resistant strains, reducing long-term disease control. When resistance is qualitative and complete - i.e. resistant strains are unaffected by the chemical and resistance requires only a single genetic change - using the lowest possible dose ensuring sufficient control is well-known as the optimal resistance management strategy. However, partial resistance (where resistant strains are still partially suppressed by the fungicide) and quantitative resistance (where a range of resistant strains are present) remain ill-understood. Here we use a model of quantitative fungicide resistance (parameterised for the economically-important fungal pathogen Zymoseptoria tritici) which handles qualitative partial resistance as a special case. We show that - for both qualitative partial resistance and quantitative resistance - although low doses are optimal for resistance management, for some model parameterisations the benefit does not outweigh the improvement in control from increasing doses. Via a machine learning approach (a gradient-boosted trees model combined with Shapley values to facilitate interpretability) we interpret the effect of parameters controlling pathogen mutation and characterising the fungicide, in addition to the timescale of interest.

evolutionary biology↗