Special Issue: “Infection in Honey Bees: Host–Pathogen Interaction and Spillover”

Honey bee health is a very important topic that has recently raised the interest of researchers [...]

Trypanin Disruption Affects the Motility and Infectivity of the Protozoan Trypanosoma cruzi

The flagellum of Trypanosomatids is an organelle that contributes to multiple functions, including motility, cell division, and host–pathogen interaction. Trypanin was first described in Trypanosoma brucei and is part of the dynein regulatory complex. TbTrypanin knockdown parasites showed motility defects in procyclic forms; however, silencing in bloodstream forms was lethal. Since TbTrypanin mutants show drastic phenotypic changes in mammalian stages, we decided to evaluate if the Trypanosoma cruzi ortholog plays a similar role by using the CRISPR-Cas9 system to generate null mutants. A ribonucleoprotein complex of SaCas9 and sgRNA plus donor oligonucleotide were used to edit both alleles of TcTrypanin without any selectable marker. TcTrypanin −/− epimastigotes showed a lower growth rate, partially detached flagella, normal numbers of nuclei and kinetoplasts, and motility defects such as reduced displacement and speed and increased tumbling propensity. The epimastigote mutant also showed decreased efficiency of in-vitro metacyclogenesis. Mutant parasites were able to complete the entire life cycle in vitro; however, they showed a reduction in their infection capacity compared with WT and addback cultures. Our data show that T. cruzi life cycle stages have differing sensitivities to TcTrypanin deletion. In conclusion, additional work is needed to dissect the motility components of T. cruzi and to identify essential molecules for mammalian stages.

Insights into the Host-Pathogen Interaction Pathways through RNA-Seq Analysis of Lens culinaris Medik. in Response to Rhizoctonia bataticola Infection

Dry root rot (Rhizoctonia bataticola) is an important disease of lentils (Lens culinaris Medik.).To gain an insight into the molecular aspects of host-pathogen interactions, the RNA-seq approach was used in lentils following inoculation with R.bataticola. The RNA-Seq has generated >450 million high-quality reads (HQRs) and nearly 96.97% were properly aligned to the reference genome. Very high similarity in FPKM (fragments per kilobase of exon per million mapped fragments) values (R > 0.9) among biological replicates showed the consistency of the RNA-Seq results. The study revealed various DEGs (differentially expressed genes) that were associated with changes in phenolic compounds, transcription factors (TFs), antioxidants, receptor kinases, hormone signals which corresponded to the cell wall modification enzymes, defense-related metabolites, and jasmonic acid (JA)/ethylene (ET) pathways. Gene ontology (GO) categorization also showed similar kinds of significantly enriched similar GO terms. Interestingly, of the total unigenes (42,606), 12,648 got assembled and showed significant hit with Rhizoctonia species. String analysis also revealed the role of various disease responsive proteins viz., LRR family proteins, LRR-RLKs, protein kinases, etc. in the host-pathogen interaction. Insilico validation analysis was performed using Genevestigator® and DEGs belonging to six major defense-response groups viz., defense-related enzymes, disease responsive genes, hormones, kinases, PR (pathogenesis related) proteins, and TFs were validated. For the first time some key miRNA targets viz. miR156, miR159, miR167, miR169, and miR482 were identified from the studied transcriptome, which may have some vital role in Rhizoctonia-based responses in lentils. The study has revealed the molecular mechanisms of the lentil/R.bataticola interactions and also provided a theoretical approach for the development of lentil genotypes resistant to R.bataticola.

Special Issue: From Host–Pathogen Interaction to Host-Directed Therapies

Despite the enormous progress made in the last few decades, infectious diseases still represent a huge challenge to human society and health systems, as evidenced by the recent SARS-CoV-2 pandemic [...]

Dual RNA-Seq of Trunk Kidneys Extracted From Channel Catfish Infected With Yersinia ruckeri Reveals Novel Insights Into Host-Pathogen Interactions

Host-pathogen intectarions are complex, involving large dynamic changes in gene expression through the process of infection. These interactions are essential for understanding anti-infective immunity as well as pathogenesis. In this study, the host-pathogen interaction was analyzed using a model of acute infection where channel catfish were infected with Yersinia ruckeri. The infected fish showed signs of body surface hyperemia as well as hyperemia and swelling in the trunk kidney. Double RNA sequencing was performed on trunk kidneys extracted from infected channel catfish and transcriptome data was compared with data from uninfected trunk kidneys. Results revealed that the host-pathogen interaction was dynamically regulated and that the host-pathogen transcriptome fluctuated during infection. More specifically, these data revealed that the expression levels of immune genes involved in Cytokine-cytokine receptor interactions, the NF-kappa B signaling pathway, the JAK-STAT signaling pathway, Toll-like receptor signaling and other immune-related pathways were significantly upregulated. Y. ruckeri mainly promote pathogenesis through the flagellum gene fliC in channel catfish. The weighted gene co-expression network analysis (WGCNA) R package was used to reveal that the infection of catfish is closely related to metabolic pathways. This study contributes to the understanding of the host-pathogen interaction between channel catfish and Y. ruckeri, more specifically how catfish respond to infection through a transcriptional perspective and how this infection leads to enteric red mouth disease (ERM) in these fish.

A System Biology Approach to Explore Host-Pathogen Interaction Under Phytochemical Cross Linkages

Phyto-signalling molecules are minute, but tangible that has rigorous roles in any plant-pathogen interaction. Certainly, most of the pathogen alters their biosynthesis, transport, degradation and cellular signalling responses to pave their virulence. Therefore, the gene expressions of such molecules with their correlated defense mechanisms were analysed in Arabidopsis thaliana against Erysiphe orontii (a potential biotroph), Botrytis cinerea (a potential necrotroph), Pseudomonas syringae (a bacterial hemibiotroph), and Phytophthora infestans (a fungal hemibiotroph) using molecular biology/ system biology techniques. The findings strongly suggested that each pathogen has its own unique infection strategy based on up-regulation and down-regulation of host phyto-signalling genes. Our studies also explored four basic pathogenic infection maps based on cross linking phyto-signalling molecules.

New Insights into the Host–Pathogen Interaction of Mycoplasma gallisepticum and Avian Metapneumovirus in Tracheal Organ Cultures of Chicken

Respiratory pathogens are a health threat for poultry. Co-infections lead to the exacerbation of clinical symptoms and lesions. Mycoplasma gallisepticum (M. gallispeticum) and Avian Metapneumovirus (AMPV) are two avian respiratory pathogens that co-circulate worldwide. The knowledge about the host–pathogen interaction of M. gallispeticum and AMPV in the chicken respiratory tract is limited. We aimed to investigate how co-infections affect the pathogenesis of the respiratory disease and whether the order of invading pathogens leads to changes in host–pathogen interaction. We used chicken tracheal organ cultures (TOC) to investigate pathogen invasion and replication, lesion development, and selected innate immune responses, such as interferon (IFN) α, inducible nitric oxide synthase (iNOS) and IFNλ mRNA expression levels. We performed mono-inoculations (AMPV or M. gallispeticum) or dual-inoculations in two orders with a 24-h interval between the first and second pathogen. Dual-inoculations compared to mono-inoculations resulted in more severe host reactions. Pre-infection with AMPV followed by M. gallispeticum resulted in prolonged viral replication, more significant innate immune responses, and lesions (p < 0.05). AMPV as the secondary pathogen impaired the bacterial attachment process. Consequently, the M. gallispeticum replication was delayed, the innate immune response was less pronounced, and lesions appeared later. Our results suggest a competing process in co-infections and offer new insights in disease processes.

Poking COVID-19: Insights on Genomic Constraints among Immune-Related Genes between Qatari and Italian Populations

Host genomic information, specifically genomic variations, may characterize susceptibility to disease and identify people with a higher risk of harm, leading to better targeting of care and vaccination. Italy was the epicentre for the spread of COVID-19 in Europe, the first country to go into a national lockdown and has one of the highest COVID-19 associated mortality rates. Qatar, on the other hand has a very low mortality rate. In this study, we compared whole-genome sequencing data of 14398 adults and Qatari-national to 925 Italian individuals. We also included in the comparison whole-exome sequence data from 189 Italian laboratory-confirmed COVID-19 cases. We focused our study on a curated list of 3619 candidate genes involved in innate immunity and host-pathogen interaction. Two population-gene metric scores, the Delta Singleton-Cohort variant score (DSC) and Sum Singleton-Cohort variant score (SSC), were applied to estimate the presence of selective constraints in the Qatari population and in the Italian cohorts. Results based on DSC and SSC metrics demonstrated a different selective pressure on three genes (MUC5AC, ABCA7, FLNA) between Qatari and Italian populations. This study highlighted the genetic differences between Qatari and Italian populations and identified a subset of genes involved in innate immunity and host-pathogen interaction.

Macrophages in Microbial Pathogenesis: Commonalities of Defense Evasion Mechanisms

Macrophages are key arsenals of the immune system against invaders. After compartmental isolation of a pathogen in phagosomes, the host immune response attempts to neutralize the pathogen. However, pathogens possess the ability to subvert these assaults and can also convert macrophages into their replicative niche. The multiple host defense evasion mechanisms employed by these pathogens like phagosome maturation arrest, molecular mimicry through secretory antigens, interference with host signaling, active radical neutralization, inhibition of phagosome acidification, alteration of programmed cell death and many other mechanisms. Macrophage biology as a part of the host-pathogen interaction has expanded rapidly in the past decade. The present review aims to shed some light upon the macrophage defense evasion strategies employed by infecting pathogens. We have also incorporated recent knowledge in the field of macrophage dynamics during infection and evolutionary perspectives of macrophage dynamics.