Elucidating the physiological and molecular characteristics of bacterial blight incitant Xanthomonas auxonopodis pv. punicae; a life threatening phytopathogen of pomegranate (Punica granatum. L) and assessment of H2O2 accumulation during host-pathogen interaction.

Bacterial blight of pomegranate caused by Xanthomonas auxonopodis pv.punicae (Xap) threaten the existence of a group of farmers for the past few decades who rely on pomegranate cultivation for their livelihood since it will cause huge yield loss. The primary focus of this study was to conduct a thorough analysis of the characterization of this blight incitant Xap. Physiological, biochemical, and molecular characteristics of six phytopathogenic strains of Xap, designated as PBF1 (PBF: Pomegranate Blight Fruit), PBF2, PBF3, PBF4, PBF5, and PBF6, isolated from the infected fruits were examined. Bacterial colonies were featured as gram-negative, yellow-pigmented circular with a glistening appearance. An attempt to determine the best culture medium, favouring bacterial proliferation was successfully done with four distinct medium, Nutrient Glucose Agar (NGA), Nutrient sucrose Agar (NSA), Yeast Dextrose Calcium Carbonate Agar (YDCA) and Yeast Glucose Calcium Carbonate Agar (YGCA) and comparatively, significant growth was found in NGA (66.66%) followed by YDCA (33%). According to the antibiotic susceptibility results, both ampicillin and streptomycin were determined as potentially effective drugs in preventing the proliferation of Xap (P 0.05). The reactive oxygen species-mediated plant immune response during host-pathogen interaction was confirmed by accessing the presence of H2O2 accumulation in infected leaves via 3,3 - diaminobenzidine (DAB) -staining technique. Bacterial isolates from this study were confirmed by two universal constitutive genes such as gyrB and 16S rRNA. From the BLAST analysis, the isolates were identified as Xap with base pair lengths of 1408bp, 1180bp, and 1159bp, which correspond to PBF1, PBF2, and PBF3, respectively. A neighbor-joining phylogenetic tree study explaining a strong phylogenetic relationship between the query sequence and closely related bacterial species.

Are COVID-19 Vaccine Boosters Needed? The Science behind Boosters.

Waning vaccine-induced immunity coupled with the emergence of SARS-CoV-2 variants has led to increases in breakthrough infections, prompting consideration for vaccine booster doses. Boosters have been reported to be safe and increase SARS-CoV-2-specific neutralizing antibody levels, but how these doses impact the trajectory of the global pandemic and herd immunity is unknown. Information on immunology, epidemiology, and equitable vaccine distribution should be considered when deciding the timing and eligibility for COVID-19 vaccine boosters.

A site assessment tool for inpatient controlled human infection models for enteric disease pathogens.

The use of the controlled human infection model to facilitate product development and to advance understanding of host-pathogen interactions is of increasing interest. While administering a virulent (or infective) organism to a susceptible host necessitates an ongoing evaluation of safety and ethical considerations, a central theme in conducting these studies in a safe and ethical manner that yields actionable data is their conduct in facilities well-suited to address their unique attributes. To that end, we have developed a framework for evaluating potential sites in which to conduct inpatient enteric controlled human infection model to ensure consistency and increase the likelihood of success.

Virulence management: Closing the feedback loop between healthcare interventions and virulence evolution.

We study the evolution of virulence of an endemic pathogen in response to healthcare interventions which affect host recovery and pathogen transmission. By anticipating the evolutionary response of the pathogen we may develop effective long-term management strategies for controlling the impact of the endemic on the society. To that end, we use standard Adaptive Dynamics techniques in an SIS model. The recovery rate and the transmission rate, both of which can be affected by healthcare interventions, are used as evolutionary control variables. The effect of interventions may be density-independent (self-help based on healthcare instructions) or density-dependent (when assistance of a healthcare worker is required). We consider the evolutionary response of the pathogen both to abrupt changes and to gradual changes in the level of healthcare intervention. Healthcare intervention is optimised for three alternative objectives: minimisation of virulence, minimisation of the probability that an infected individual dies of the disease, and total eradication of the endemic. We find that the optimal strategy may depend on the objective. High levels of healthcare intervention may eradicate the pathogen, but this option may not be available for budgetary reasons or otherwise. Counterintuitively, to minimise virulence, one should keep healthcare interventions at a minimum, while to minimise the probability for an infected individual to die of the disease, both low and high levels of healthcare intervention suffice. Changes in the level of healthcare intervention should be implemented fast (not gradually) in order to avoid sudden changes in pathogen evolution and the possible emergence of multiple simultaneously coexisting pathogen strains.

Land-use change and rodent-borne diseases: hazards on the shared socioeconomic pathways.

Land-use change has a direct impact on species survival and reproduction, altering their spatio-temporal distributions. It acts as a selective force that favours the abundance and diversity of reservoir hosts and affects host-pathogen dynamics and prevalence. This has led to land-use change being a significant driver of infectious diseases emergence. Here, we predict the presence of rodent taxa and map the zoonotic hazard (potential sources of harm) from rodent-borne diseases in the short and long term (2025 and 2050). The study considers three different land-use scenarios based on the shared socioeconomic pathways narratives (SSPs): sustainable (SSP1-Representative Concentration Pathway (RCP) 2.6), fossil-fuelled development (SSP5-RCP 8.5) and deepening inequality (SSP4-RCP 6.0). We found that cropland expansion into forest and pasture may increase zoonotic hazards in areas with high rodent-species diversity. Nevertheless, a future sustainable scenario may not always reduce hazards. All scenarios presented high heterogeneity in zoonotic hazard, with high-income countries having the lowest hazard range. The SSPs narratives suggest that opening borders and reducing cropland expansion are critical to mitigate current and future zoonotic hazards globally, particularly in middle- and low-income economies. Our study advances previous efforts to anticipate the emergence of zoonotic diseases by integrating past, present and future information to guide surveillance and mitigation of zoonotic hazards at the regional and local scale. This article is part of the theme issue 'Infectious disease macroecology: parasite diversity and dynamics across the globe'.

Transcriptome-level assessment of the impact of deformed wing virus on honey bee larvae.

Deformed wing virus (DWV) prevalence is high in honey bee (Apis mellifera) populations. The virus infects honey bees through vertical and horizontal transmission, leading to behavioural changes, wing deformity, and early mortality. To better understand the impacts of viral infection in the larval stage of honey bees, artificially reared honey bee larvae were infected with DWV (1.55 × 1010 copies/per larva). No significant mortality occurred in infected honey bee larvae, while the survival rates decreased significantly at the pupal stage. Examination of DWV replication revealed that viral replication began at 2 days post inoculation (d.p.i.), increased dramatically to 4 d.p.i., and then continuously increased in the pupal stage. To better understand the impact of DWV on the larval stage, DWV-infected and control groups were subjected to transcriptomic analysis at 4 d.p.i. Two hundred fifty-five differentially expressed genes (DEGs) (fold change ≥ 2 or ≤ -2) were identified. Of these DEGs, 168 genes were downregulated, and 87 genes were upregulated. Gene Ontology (GO) analysis showed that 141 DEGs (55.3%) were categorized into molecular functions, cellular components and biological processes. One hundred eleven genes (38 upregulated and 73 downregulated) were annotated by KO (KEGG Orthology) pathway mapping and involved metabolic pathways, biosynthesis of secondary metabolites and glycine, serine and threonine metabolism pathways. Validation of DEGs was performed, and the related gene expression levels showed a similar tendency to the DEG predictions at 4 d.p.i.; cell wall integrity and stress response component 1 (wsc1), cuticular protein and myo-inositol 2-dehydrogenase (iolG) were significantly upregulated, and small conductance calcium-activated potassium channel protein (SK) was significantly downregulated at 4 d.p.i. Related gene expression levels at different d.p.i. revealed that these DEGs were significantly regulated from the larval stage to the pupal stage, indicating the potential impacts of gene expression levels from the larval to the pupal stages. Taken together, DWV infection in the honey bee larval stage potentially influences the gene expression levels from larvae to pupae and reduces the survival rate of the pupal stage. This information emphasizes the consequences of DWV prevalence in honey bee larvae for apiculture.

Recent advances in rotavirus reverse genetics and its utilization in basic research and vaccine development.

Rotaviruses are segmented double-stranded RNA viruses with a high frequency of gene reassortment, and they are a leading cause of global diarrheal deaths in children less than 5 years old. Two-thirds of rotavirus-associated deaths occur in low-income countries. Currently, the available vaccines in developing countries have lower efficacy in children than those in developed countries. Due to added safety concerns and the high cost of current vaccines, there is a need to develop cost-effective next-generation vaccines with improved safety and efficacy. The reverse genetics system (RGS) is a powerful tool for investigating viral protein functions and developing novel vaccines. Recently, an entirely plasmid-based RGS has been developed for several rotaviruses, and this technological advancement has significantly facilitated novel rotavirus research. Here, we review the recently developed RGS platform and discuss its application in studying infection biology, gene reassortment, and development of vaccines against rotavirus disease.

Dynamic Regulatory Event Mining by iDREM in Large-Scale Multi-omics Datasets During Biotic and Abiotic Stress in Plants.

The system-wide complexity of genome regulation encoding the organism phenotypic diversity is well understood. However, a major challenge persists about the appropriate method to describe the systematic dynamic genome regulation event utilizing enormous multi-omics datasets. Here, we describe Interactive Dynamic Regulatory Events Miner (iDREM) which reconstructs gene-regulatory networks from temporal transcriptome, proteome, and epigenome datasets during stress to envisage "master" regulators by simulating cascades of temporal transcription-regulatory and interactome events. The iDREM is a Java-based software that integrates static and time-series transcriptomics and proteomics datasets, transcription factor (TF)-target interactions, microRNA (miRNA)-target interaction, and protein-protein interactions to reconstruct temporal regulatory network and identify significant regulators in an unsupervised manner. The hidden Markov model detects specialized manipulated pathways as well as genes to recognize statistically significant regulators (TFs/miRNAs) that diverge in temporal activity. This method can be translated to any biotic or abiotic stress in plants and animals to predict the master regulators from condition-specific multi-omics datasets including host-pathogen interactions for comprehensive understanding of manipulated biological pathways.

Kinship networks of seed exchange shape spatial patterns of plant virus diversity.

By structuring farmers' informal networks of seed exchange, kinship systems play a key role in the dynamics of crop genetic diversity in smallholder farming systems. However, because many crop diseases are propagated through infected germplasm, local seed systems can also facilitate the dissemination of seedborne pathogens. Here, we investigate how the interplay of kinship systems and local networks of germplasm exchange influences the metapopulation dynamics of viruses responsible for the cassava mosaic disease (CMD), a major threat to food security in Africa. Combining anthropological, genetic and plant epidemiological data, we analyzed the genetic structure of local populations of the African cassava mosaic virus (ACMV), one of the main causal agents of CMD. Results reveal contrasted patterns of viral diversity in patrilineal and matrilineal communities, consistent with local modes of seed exchange. Our results demonstrate that plant virus ecosystems have also a cultural component and that social factors that shape regional seed exchange networks influence the genetic structure of plant virus populations.

Persistence assessment of SARS-CoV-2-specific IgG antibody in recovered COVID-19 individuals and its association with clinical symptoms and disease severity: A prospective longitudinal cohort study.

BACKGROUND: Antibodies play an important role in neutralizing invading pathogens and protecting the host against re-infection. Thus, the accurate assessment of antibodies during a pandemic can provide important evidence for monitoring pathogen exposure, understanding the role of antibodies in protective immunity, and helping vaccine development. METHODS: In this study, 96 west Iranian recovered COVID-19 subjects were recruited and, based on clinical symptoms and disease severity, categorized into three different groups: mild, moderate, and severe. In addition, the presence and dynamic change of SARS-CoV-2-specific IgG antibody three, four-, and six months post symptom onset (PSO) were measured. Also, the association between IgG antibody titer with clinical symptoms and disease severity was examined. RESULTS: Although in real-time RT-PCR-positive samples negative IgG antibody results were found, most subjects mount humoral immune responses that could raise a robust SARS-CoV-2-specific IgG antibody. Furthermore, this antibody persisted in the serum of most recovered COVID-19 subjects at least six months PSO and demonstrated little to no decrease. Also, specific IgG antibody titer was strongly correlated with clinical symptoms and disease severity. CONCLUSIONS: These results provide an insight into the presence and persistence of the SARS-CoV-2-specific IgG antibody. Although serological tests could not be used as the primary diagnostic test, they may support real-time RT-PCR results. Also, they could be used for diagnosing COVID-19 subjects tested later outside of the optimal period. Thus, the SARS-CoV-2-specific IgG antibody is an excellent marker of COVID-19 infection or vaccination and provides an additional diagnostic tool for verifying results and helps monitor and control COVID-19 spread.

Sex hormones, autoimmunity and gender disparity in COVID-19.

The Coronavirus disease 2019 (COVID-19) pandemic has majorly contributed to massive and widespread mortality. Epidemiological data strongly indicates a sex-based disparity in COVID-19 clinical outcomes, with women having lower infection and hospitalisation rates, coupled with better prognosis and lesser mortality. This disparity may be explained by several mechanisms including differences in innate and adaptive immune responses, genetic factors, and an interplay between sex hormones and immune effectors, as well as gender-specific behaviour differences. These pathways, particularly the immunological divergence in response to viral infection, could potentially influence not only COVID-19 pathogenesis and disease course, but also the response to antiviral drugs and vaccines. Furthermore, factors that confer a protective advantage against COVID-19 may be exploited to develop therapeutic strategies to improve clinical outcomes in COVID-19.

Similarities and differences between HIV and SARS-CoV-2.

In the last 50 years we have experienced two big pandemics, the HIV pandemic and the pandemic caused by SARS-CoV-2. Both pandemics are caused by RNA viruses and have reached us from animals. These two viruses are different in the transmission mode and in the symptoms they generate. However, they have important similarities: the fear in the population, increase in proinflammatory cytokines that generate intestinal microbiota modifications or NETosis production by polymorphonuclear neutrophils, among others. They have been implicated in the clinical, prognostic and therapeutic attitudes.

Similarities and Dissimilarities of COVID-19 and Other Coronavirus Diseases.

In less than two decades, three deadly zoonotic coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2, have emerged in humans, causing SARS, MERS, and coronavirus disease 2019 (COVID-19), respectively. The current COVID-19 pandemic poses an unprecedented crisis in health care and social and economic development. It reinforces the cruel fact that CoVs are constantly evolving, possessing the genetic malleability to become highly pathogenic in humans. In this review, we start with an overview of CoV diseases and the molecular virology of CoVs, focusing on similarities and differences between SARS-CoV-2 and its highly pathogenic as well as low-pathogenic counterparts. We then discuss mechanisms underlying pathogenesis and virus-host interactions of SARS-CoV-2 and other CoVs, emphasizing the host immune response. Finally, we summarize strategies adopted for the prevention and treatment of CoV diseases and discuss approaches to develop effective antivirals and vaccines.

Hypothesis: Sex-Related Differences in ACE2 Activity May Contribute to Higher Mortality in Men Versus Women With COVID-19.

Angiotensin-converting enzyme 2 (ACE2) facilitates the cellular entry of the severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), which causes the coronavirus-2019 (COVID-19) disease. Recent reports have shown worse outcomes in men with COVID-19 infection compared to women. We review the hypothesis that sex-related differences in outcomes in COVID-19 are due to different activity of ACE2 between men and women. We also show that studies in humans have demonstrated no significant difference in serum ACE2 levels between healthy men and women. However, men with hypertension and heart failure typically have higher level of serum ACE2 activity compared to women. We hypothesize that the worse outcomes in men with COVID-19 compared to women is likely due to higher prevalence of hypertension and heart failure among men compared to women. To test this hypothesis, studies to compare the outcomes of COVID-19 infection between men and women with no preexisting heart diseases are needed.

High-Quality Genome Resource of the Pathogen of Diaporthe (Phomopsis) phragmitis Causing Kiwifruit Soft Rot.

Diaporthe spp. are critical plant pathogens that cause wood cankers, wilt, dieback, and fruit rot in a wide variety of economic plant hosts and are regarded as one of the most acute threats faced by the kiwifruit industry worldwide. Diaporthe phragmitis NJD1 is a highly pathogenic isolate of soft rot of kiwifruit. Here, we present a high-quality genome-wide sequence of D. phragmitis NJD1 that was assembled into 28 contigs containing a total size of 58.33 Mb and N50 length of 3.55 Mb. These results lay a solid foundation for understanding host-pathogen interaction and improving disease management strategies.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Why does COVID-19 kill more elderly men than women? Is there a role for testosterone?

BACKGROUND: Recent epidemiological data indicate that there may be a gender predisposition to COVID-19, with men predisposed to being most severely affected, and older men accounting for most deaths. OBJECTIVES: Provide a review of the research literature, propose hypotheses, and therapies based on the potential link between testosterone (T) and COVID-19 induced mortality in elderly men. MATERIALS AND METHODS: A search of publications in academic electronic databases, and government and public health organization web sites on T, aging, inflammation, severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) infection, and COVID-19 disease state and outcomes was performed. RESULTS: The link between T, the immune system, and male aging is well-established, as is the progressive decline in T levels with aging. In women, T levels drop before menopause and variably increase with advanced age. Elevated IL-6 is a characteristic biomarker of patients infected with COVID-19 and has been linked to the development of the acute respiratory distress syndrome (ARDS). Thus far, half of the admitted COVID-19 patients developed ARDS, half of these patients died, and elderly male patients have been more likely to develop ARDS and die. Low T is associated with ARDS. These data suggest that low T levels may exacerbate the severity of COVID-19 infection in elderly men. It may also stand to reason that normal T levels may offer some protection against COVID-19. SARS-CoV-2 binds to the angiotensin-converting enzyme 2, present in high levels in the testis. CONCLUSION: At present, it is not known whether low T levels in aging hypogonadal males create a permissive environment for severe responses to COVID-19 infection or if the virus inhibits androgen formation. Given the preponderance of COVID-19 related mortality in elderly males, additional testing for gonadal function and treatment with T may be merited.

SARS-CoV-2, testosterone and frailty in males (PROTEGGIMI): A multidimensional research project.

Preliminary published data depict a much greater prevalence of males with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) referred for intensive care unit admission and severe sequelae in several countries. In this context, males seem to not only be more susceptible to the infection compared to female subjects, at least in Western countries, but their case fatality rate attributable to SARS-CoV-2 infection is also highest. Therefore, we may speculate that the different hormonal milieu could have a more profound pathophysiological role in association with SARS-CoV-2, with endogenous testosterone leaving men more prone to develop more serious complications related to the SARS-CoV-2 infection. Another option is that SARS-CoV-2 infection per se causes an acute stage of male hypogonadism, the depletion of androgenic action triggering serious or an even fatal course of the disease. Therefore, we strongly advocate the development of a prospective multidimensional andrological translational research project in men, which we called the PROTEGGIMI study. In this Opinion Article, we will not only highlight novel research activity in this area but also invite other researchers and learned scientific societies to join us in our efforts to understand an important and very newly discovered gap in knowledge, which may have serious implications for the lives of millions of men.

Caution in the management of SARS-CoV-2 infection in males.

The coronavirus 2 (SARS-CoV-2) pandemic carries clinical, economic, and social burdens that are currently being disclosed. The key steps of virus life cycle have been recently clarified, highlighting the role of host type 2 angiotensin-converting enzyme (ACE2) and TMPRSS2 serine protease in virus-cell binding and entry, respectively. Importantly, major concerns derive from the androgen-dependent tissue-expression of both TMPRSS2 and ACE2, suggesting a differential clinical course of the infection between genders. In agreement with this model, available epidemiological data show that the disease in males has an higher risk to display an heavier pattern and associates with both an increased access to critical care unit and higher mortality rate. In this opinion article, available evidence linking the androgen activity with the gender differences observed in SARS-CoV-2 infection are discussed, hypothesizing possible therapeutic approaches in male based on the disruption of androgen signaling. On these bases, gender-specific recommendations for the management of male patients affected by SARS-CoV-2 infection are warmly suggested, in order to improve the clinical course of the disease.

Worse progression of COVID-19 in men: Is testosterone a key factor?

BACKGROUND: The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease 2019 (COVID-19) seems to have a worse clinical course among infected men compared with women, thus highlighting concerns about gender predisposition to serious prognosis. Therefore, androgens, particularly testosterone (T), could be suspected as playing a critical role in driving this excess of risk. However, gonadal function in critically ill men is actually unknown, mainly because serum T concentration is not routinely measured in clinical practice, even more in this clinical context. OBJECTIVE: To overview on possible mechanisms by which serum T levels could affect the progression of COVID-19 in men. METHODS: Authors searched PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library, Google, and institutional websites for medical subject headings terms and free text words referred to "SARS-CoV-2," "COVID-19," "testosterone," "male hypogonadism," "gender" "immune system," "obesity," "thrombosis" until May 19th 2020. RESULTS: T, co-regulating the expression of angiotensin-converting enzyme 2 and transmembrane protease serine 2 in host cells, may facilitate SARS-CoV-2 internalization. Instead, low serum T levels may predispose to endothelial dysfunction, thrombosis and defective immune response, leading to both impaired viral clearance and systemic inflammation. Obesity, one of the leading causes of severe prognosis in infected patients, is strictly associated with functional hypogonadism, and may consistently strengthen the aforementioned alterations, ultimately predisposing to serious respiratory and systemic consequences. DISCUSSION AND CONCLUSION: T in comparison to estrogen may predispose men to a widespread COVID-19 infection. Low serum levels of T, which should be supposed to characterize the hormonal milieu in seriously ill individuals, may predispose men, especially elderly men, to poor prognosis or death. Further studies are needed to confirm these pathophysiological assumptions and to promptly identify adequate therapeutic strategies.