Host Pathogen Research Articles

The 24-kDa subunit of mitochondrial complex I regulates growth, microsclerotia development, stress tolerance, and virulence in Verticillium dahliae

BackgroundThe complete mitochondrial respiratory chain is a precondition for maintaining cellular energy supply, development, and metabolic balance. Due to the evolutionary differentiation of complexes and the semi-autonomy of mitochondria, respiratory chain subunits have become critical targets for crop improvement and fungal control. In fungi, mitochondrial complex I mediates growth and metabolism. However, the role of this complex in the pathogenesis of phytopathogenic fungi is largely unknown.ResultsIn this study, we identified the NADH: ubiquinone oxidoreductase 24-kDa subunit (VdNuo1) of complex in vascular wilt pathogen, Verticillium dahliae, and examined its functional conservation in phytopathogenic fungi. Based on the treatments with respiratory chain inhibitors, the mitochondria-localized VdNuo1 was confirmed to regulate mitochondrial morphogenesis and homeostasis. VdNuo1 was induced during the different developmental stages in V. dahliae, including hyphal growth, conidiation, and melanized microsclerotia development. The VdNuo1 mutants displayed variable sensitivity to stress factors and decreased pathogenicity in multiple hosts, indicating that VdNuo1 is necessary in stress tolerance and full virulence. Comparative transcriptome analysis demonstrated that VdNuo1 mediates global transcriptional effects, including oxidation and reduction processes, fatty acid, sugar, and energy metabolism. These defects are partly attributed to impairments of mitochondrial morphological integrity, complex assembly, and related functions. Its homologue (CgNuo1) functions in the vegetative growth, melanin biosynthesis, and pathogenicity of Colletotrichum gloeosporioides; however, CgNuo1 does not restore the VdNuo1 mutant to normal phenotypes.ConclusionsOur results revealed that VdNuo1 plays important roles in growth, metabolism, microsclerotia development, stress tolerance, and virulence of V. dahliae, sharing novel insight into the function of complex I and a potential fungicide target for pathogenic fungi.

Managing tomato bacterial wilt through pathogen suppression and host resistance augmentation using microbial peptide

The increasing health and environmental risks associated with synthetic chemical pesticides necessitate the exploration of safer, sustainable alternatives for plant protection. This study investigates a novel biosynthesized antimicrobial peptide (AMP) from Lactiplantibacillus argentoratensis strain IT, identified as the amino acid chain PRKGSVAKDVLPDPVYNSKLVTRLINHLMIDGKRG, for its efficacy in controlling bacterial wilt (BW) disease in tomato (Solanum lycopersicum) caused by Ralstonia solanacearum. Our research demonstrates that foliar application of this AMP at a concentration of 200 ppm significantly reduces disease incidence by 49.3% and disease severity by 45.8%. Scanning electron microscopy revealed severe morphological disruptions in the bacterial cells upon exposure to the AMP. Additionally, the AMP enhanced host resistance by elevating defense enzyme activities, leading to notable improvements in plant morphology, including a 95.5% increase in plant length, a 20.1% increase in biomass, and a 96.69% increase in root length. This bifunctional AMP provides dual protection by exerting direct antimicrobial activity against the pathogen and eliciting plant defense mechanisms. These findings underscore the potential of this biologically sourced AMP as a natural agent for combating plant diseases and promoting growth in tomato crops. To the best of our knowledge, this is the first study to demonstrate the use of a foliar spray application of a biosynthesized microbial peptide as biocontrol agent against R. solanacearum. This interaction not only highlights its biocontrol efficacy but also its role in promoting the growth of Solanum lycopersicum thereby increasing overall agricultural yield.

A Virulence Factor from Sclerotinia sclerotiorum Targets the Host Chloroplast Proteins to Promote Infection

Chloroplasts are not only places for photosynthesis, but also participate in plant immunity and are important targets of pathogens. Pathogens secrete chloroplast-targeted proteins (CTPs) that disrupt host immunity and promote infection. Sclerotinia sclerotiorum (Lib.) de Bary is a phytopathogenic fungus with a broad host range. However, little is known about the pathogenic mechanisms underlying this wide host range. In this study, we investigated the role of Chloroplast-Targeted Protein 1 (SsCTP1) secreted by S. sclerotiorum in pathogenesis, which inhibits plant immunity and promotes pathogen infections. SsCTP1 was highly up-regulated during the early stages of S. sclerotiorum infection in various hosts, and its transient expression in Nicotiana benthamiana revealed that it was predominantly localized within chloroplasts. Mutants with SsCTP1 deletion exhibited a similar growth rate and colony morphology to the wild type, but significantly reduced pathogenicity in various hosts. Moreover, SsCTP1 inhibited chitin-induced callose deposition and defense gene expression, and enhanced sensitivity to S. sclerotiorum in N. benthamiana. Similarly, transgenic Arabidopsis thaliana overexpressing SsCTP1 displayed an increased susceptibility to S. sclerotiorum. Furthermore, two host proteins that interact with SsCTP1, Coproporphyrinogen-III oxidase (GmCPX), and shikimate kinase 2 (GmSKL2) were identified by screening the soybean cDNA library, and these interactions were confirmed in vivo. Importantly, the silencing of NbCPX by virus-induced gene silencing enhanced N. benthamiana resistance to S. sclerotiorum. Our results indicate that SsCTP1 is an important pathogenic factor that contributes to the wide host range of S. sclerotiorum and may inhibit plant immunity by targeting the chloroplast proteins GmCPX and GmSKL2, which are ubiquitous in host plants.

Factors associated with disease in farmed and wild salmonids caused by Tenacibaculum maritimum: a scoping review

IntroductionYellow mouth disease, caused by Tenacibaculum maritimum, is an important disease of farmed salmonids. Disease management currently necessitates the use of antimicrobials, raising concerns about antimicrobial resistance (AMR) in aquatic and potentially terrestrial environments. Identifying management, production, environmental, and other factors associated with the development of yellow mouth in salmonids will help to elucidate disease control strategies and decrease the economic and environmental burden of its treatment. The objective of this scoping review was to synthesize the available literature to identify factors associated with disease in farmed and wild salmonids from T. maritimum.MethodsThe scoping review followed the framework outlined in the Joanna Briggs Institute Reviewer’s Manual and PRSIMA-ScR reporting guidelines. The protocol was developed a priori in consultation with a librarian and was used to search Environment Complete®, Earth, Atmospheric, and Aquatic Science®, Scopus®, and Web of Science™ databases on July 21, 2022, and again on April 27, 2023. Articles were included if they focused on T. maritimum infection in salmonids and discussed factors (environmental, management, or other) that impacted the disease and/or organism of interest.ResultsTwenty-five articles were included for review. Over half were published within the last five years (n=14/25). The included articles revealed a complex interplay of salmonid (host)-specific factors (age/size), management practices (vaccination, marine transfer, stocking density, gill/body abrasion), environmental conditions (water temperature, oxygenation, salinity, algal blooms, vectors), and microbial dynamics (load, co-infections, strain, biofilms, microbiome) influencing T. maritimum infections. Only one study conducted multivariable analysis to understand this complex interplay between the diverse factors that impact infection with T. maritimum.DiscussionThe review highlights the complex, multifactorial nature of T. maritimum infections, including the interplay of host biology, environmental factors, and pathogen characteristics. A comprehensive approach incorporating both management and environmental components is essential to mitigate T. maritimum infections in salmonid production.

Transcriptomic Profiling Reveals Altered Expression of Genes Involved in Metabolic and Immune Processes in NDV-Infected Chicken Embryos

Objective: The poultry industry is significantly impacted by viral infections, particularly Newcastle Disease Virus (NDV), which leads to substantial economic losses. It is essential to comprehend how the sequence of development affects biological pathways and how early exposure to infections might affect immune responses. Methods: This study employed transcriptome analysis to investigate host–pathogen interactions by analyzing gene expression changes in NDV-infected chicken embryos’ lungs. Result: RNA-Seq reads were aligned with the chicken reference genome (Galgal7), revealing 594 differentially expressed genes: 264 upregulated and 330 downregulated. The most overexpressed genes, with logFC between 8.15 and 8.75, included C8A, FGG, PIT54, FETUB, APOC3, and FGA. Notably, downregulated genes included BPIFB3 (−4.46 logFC) and TRIM39.1 (−4.26 logFC). The analysis also identified 29 novel transcripts and 20 lncRNAs that were upregulated. Gene Ontology and KEGG pathways’ analyses revealed significant alterations in gene expression related to immune function, metabolism, cell cycle, nucleic acid processes, and mitochondrial activity due to NDV infection. Key metabolic genes, such as ALDOB (3.27 logFC), PRPS2 (2.66 logFC), and XDH (2.15 logFC), exhibited altered expression patterns, while DCK2 (−1.99 logFC) and TK1 (−2.11 logFC) were also affected. Several immune-related genes showed significant upregulation in infected lung samples, including ALB (6.15 logFC), TLR4 (1.86 logFC), TLR2 (2.79 logFC), and interleukin receptors, such as IL1R2 (3.15 logFC) and IL22RA2 (1.37 logFC). Conversely, genes such as CXCR4 (−1.49 logFC), CXCL14 (−2.57 logFC), GATA3 (−1.51 logFC), and IL17REL (−2.93 logFC) were downregulated. The higher expression of HSP genes underscores their vital role in immune responses. Conclusion: Comprehension of these genes’ interactions is essential for regulating viral replication and immune responses during infections, potentially aiding in the identification of candidate genes for poultry breed improvement amidst NDV challenges.

Signature of viral fossils: a comparative genomics approach to understand the diversity of endogenous retroviruses in bats

Endogenous retroviruses (ERVs) are traces of past viral infections commonly found in vertebrate genomes. Many ERVs are tightly regulated by the host genomes and co-opted for various functions within the hosts. Bats are the only true volant mammals, with the smallest mammalian genomes and a high fraction of ERVs within the genomes. They are important hosts for various zoonotic viral pathogens and can effectively modulate their immune response to tolerate viral infections. Integrations of retroviruses have been implicated as one of the mechanisms by which bats have co-evolved strategies to combat viral infections. In this study, we investigated the diversity of ERVs in over 40 publicly available bat genomes to understand the distribution and the evolution of ERVs within bats. We observed all classes of ERVs within bat genomes including even the complex lenti retroviruses. Alpha and spuma retroviruses which are generally considered rare in mammals, were common within bats. We observed a positive correlation between bat genome size and length of ERV elements. Interestingly, nearly 30 % of the ERVs within bats are intact suggesting a recent origin or co-option by the host genome. Future studies focusing on comparative genomic and experimental data will be critical to understand the role of these ERVs in host genome evolution.

Unraveling the genetic basis of Rhizobium rhizogenes-mediated transformation and hairy root formation in rose using a genome-wide association study

Key MessageMultiple QTLs reveal the polygenic nature of R. rhizogenes-mediated transformation and hairy root formation in roses, with five key regions explaining 12.0–26.9% of trait variability and transformation-related candidate genes identified.Understanding genetic mechanisms of plant transformation remains crucial for biotechnology. This is particularly relevant for roses and other woody ornamentals that exhibit recalcitrant behavior in transformation procedures. Rhizobium rhizogenes-mediated transformation leading to hairy root (HR) formation provides an excellent model system to study transformation processes and host–pathogen interactions. Therefore, this study aimed to identify quantitative trait loci (QTLs) associated with HR formation and explore their relationship with adventitious root (AR) formation in rose as a model for woody ornamentals. A diversity panel of 104 in vitro grown rose genotypes was transformed with R. rhizogenes strain ATCC 15834 carrying a green fluorescent protein reporter gene. Phenotypic data on callus and root formation were collected for laminae and petioles. A genome-wide association study using 23,419 single-nucleotide polymorphism markers revealed significant QTLs on chromosomes one and two for root formation traits. Five key genomic regions explained 12.0–26.9% of trait variability, with some peaks overlapping previously reported QTLs for AR formation. This genetic overlap was supported by weak to moderate correlations between HR and AR formation traits, particularly in petioles. Candidate gene identification through literature review and transcriptomic data analysis revealed ten candidate genes involved in bacterial response, hormone signaling, and stress responses. Our findings provide new insights into the genetic control of HR formation in roses and highlight potential targets for improving transformation efficiency in ornamental crops, thereby facilitating future research and breeding applications.

Rare case report: Perforation Gallbladder Peritonitis Caused by Enterococcus avium at Prof. Dr. I.G.N.G Ngoerah Hospital

Enterococcus is a gram-positive, catalase-negative, and non-spore-bearing bacteria that generally live in the digestive tract of humans and animals. Enterococcus avium has rarely been detected infecting humans. Enterococcus avium has low virulence and is an opportunistic pathogen in hosts with weakeness immune systems. The most frequently reported sites of entry are the biliary tract and stomach. Peritonitis caused by Enterococcus avium is rare. Infection generally occurs through bacterial colonization. We report the first case of a patient with Gallbladder perforation resulting in peritonitis caused by Enterococcus avium at Prof. dr.I.G.N.G Ngoerah Hospital. Case Presentation: A 67-year-old Balinese man with peritonitis due to gallbladder perforation caused by infection Enterococcus avium. Previously the patient complained of stomach pain, and the patient had a history of gallstone disease. Subsequently, surgery was performed on the patient. During the operation, pus and perforation of the gallbladder were found. The pus specimen was examined in the microbiology laboratory, and the Enterococcus avium bacteria was identified as a significant agent causing the infection. In this case, ampicillin was recommended as therapy. After 5 days of antibiotics, the patient’s condition improved. Conclusion: Enterococcus avium has low virulence and is an opportunistic pathogen in an immunocompromised host. The finding case will be beneficial to clinicians because it provides additional information about the lesser-known Enterococcus avium.

Big Data Visualization for Black Sigatoka Disease of Bananas and Pathogen–Host Interactions (PHI) of Other Plants

Black sigatoka is a leaf spot disease affecting banana plants that has caused significant yield reductions of up to 50% (Arman et al., 2023). This research presents data visualizations of 8,761 data points related to black sigatoka in banana plants, encompassing attributes such as time, canopy temperature, and relative humidity. The paper also reviews related work, including the application of data mining to plant studies, the use of deep learning neural networks for plant disease data, and the use of machine learning for predicting crop yields and detecting disease. Additionally, it presents big data visualizations for 20,952 values obtained from the web-accessible Pathogen–Host Interactions database (PHI-base), covering various plant disease categories and providing an epidemiological analysis of prevalent causative agents in specific plant diseases.

Closely Related Brucella Species Widely Differ in their Vegetative and Intracellular Growth.

Growth rate is a key prokaryotic trait that allows for estimating fitness and understanding cell metabolism. While it has been well studied in model organisms, there is limited data on slow-growing bacteria. In particular, there is a lack of quantitative studies on Brucella species. This genus includes important microorganisms that are causative agents of brucellosis, one of the most widespread bacterial zoonoses, affecting several species of animals, including humans. Brucella species exhibit approximately 97% genomic similarity. Despite this, Brucella species show different host preferences, zoonotic risks, and pathogenicity. After more than one hundred years of research, numerous aspects of Brucella biology, such as in vivo and in vitro growth, remain poorly characterized. In this work, we analyzed vegetative and intracellular growth of the classical Brucella species (B. abortus, B. melitensis, B. suis, B. ovis, and B. canis). Strikingly, each species displayed distinct growth parameters in culture. Doubling time (DT) ranged from 2.7 hs-1 in B. suis to 18h-1 for B. ovis. In the context of intracellular infection of J774A.1 phagocytic cells, DT was longer, but it widely varied across species, closely correlating with the growth observed in vitro. Overall, and despite high genome similarity, we also found species-specific growth parameters in the intracellular cell cycle.

The Hemibiotrophic Apple Scab Fungus Venturia inaequalis Induces a Biotrophic Interface but Lacks a Necrotrophic Stage

Microscopic evidence demonstrated a strictly biotrophic lifestyle of the scab fungus Venturia inaequalis on growing apple leaves and characterised its hemibiotrophy as the combination of biotrophy and saprotrophy not described before. The pathogen–host interface was characterised by the formation of knob-like structures of the fungal stroma appressed to epidermal cells as early as 1 day after host penetration, very thin fan-shaped cells covering large parts of the host cell lumen, and enzymatic cuticle penetration from the subcuticular space limited to the protruding conidiophores. The V. inaequalis cell wall had numerous orifices, facilitating intimate contact with the host tissue. Pathogen-induced modifications of host cells included partial degradation of the cell wall, transition of epidermal cells into transfer cells, modification of epidermal pit fields to manipulate the flow of nutrients and other compounds, and formation of globular protuberances of mesophyll cells without contact with the pathogen. The non-haustorial biotrophy was characterised by enlarged areas of intimate contact with host cells, often mediated by a matrix between the pathogen and plant structures. The new microscopic evidence and information on the pathogens’ biochemistry and secretome from the literature gave rise to a model of the lifestyle of V. inaequalis, lacking a necrotrophic stage that covers and explains its holomorphic development.

Ease and Limitations in Using Environmental DNA to Track the Spread of Invasive Host–Parasite Complexes: A Case Study of the Freshwater Fish Pseudorasbora parva and the Cryptic Fungal Parasite Sphaerothecum destruens

The spread of non-native species threatens biodiversity and exacerbates societal challenges like food security. To address this, effective conservation programs require detection methods that are easy to implement, accurate, and non-invasive. Over the past 15 years, environmental DNA (eDNA) techniques have gained popularity, surpassing traditional sampling methods. In this context, our study focused on tracking the invasive host–pathogen complex Pseudorasbora parva and Sphaerothecum destruens using eDNA metabarcoding. We collected water samples from freshwater canals over five months in the Camargue region, and once in Corsica Island, both in southern France. Total DNA was extracted from filtered water samples, and PCR-amplicons were sequenced using Illumina or Nanopore technologies. Our results revealed a high detection rate of P. parva in lentic ecosystems, aligning with habitat preferences of this small freshwater fish. Additionally, the detection rate in Camargue increased in May and June, likely due to the peak of the spawning season, which leads to more DNA being released into the environment (i.e., concentration and interaction of individuals). While eDNA successfully detected this invasive fish, we were unable to detect its cryptic fungal parasite, S. destruens, highlighting the challenges of identifying intracellular and cryptic fungal pathogens through eDNA methods.

What’s love got to do with it? A biophilia-based approach to zoonoses prevention through a conservation lens

E.O. Wilson coined the term biophilia, defining it as an innate affinity to the natural world. The concept of nature connectedness is used in environmental psychology as a measure of feelings and self-perceptions of connectedness to nature. Researchers have found a wide variety of positive effects associated with nature connectedness, including better mental health and wellbeing, increased altruistic and cooperative behavior, and heightened empathy. When these feelings of empathy are directed toward nature and applied to conservation actions, they can overcome the effects of compassion collapse, a phenomenon observed to lower study participants willingness to engage in altruistic behavior when there are many or diffuse victims of a disaster. Biophilia is an important concept in conservation, but it has not been widely applied to zoonoses prevention. The public health community has often relied on fear-based (biophobic) messages, which can drive the very interactions they were intended to avoid (e.g., media reports of bat zoonoses leading to culling activities and destruction of bat habitat) and exacerbate the ecological drivers of spillover. Communication strategies rooted in biophilia may be more effective at generating empathy for both ecological and human communities, leading to greater willingness to leave zoonotic pathogen hosts and their habitats alone, further reducing spillover events and the ecological conditions that make spillover more likely. Given the intertwined nature of human and ecological health, it is critical that the conservation and public health communities speak in a unified voice.

Global Lipidomics Reveals the Lipid Composition Heterogeneity of Extracellular Vesicles from Drug-Resistant Leishmania

Background: The rise of drug-resistant Leishmania strains presents a significant challenge in the treatment of Leishmaniasis, a neglected tropical disease. Extracellular vesicles (EVs) produced by these parasites have gained attention for their role in drug resistance and host–pathogen interactions. Methods: This study developed and applied a novel lipidomics workflow to explore the lipid profiles of EVs from three types of drug-resistant Leishmania infatum strains compared to a wild-type strain. EVs were isolated through ultracentrifugation, and their lipid content was extracted using a modified Matyash protocol. LC-MS analysis was performed, and data processing in MS-DIAL enabled lipid identification and quantification. Statistical analysis in MetaboAnalyst revealed strain-specific lipid alterations, highlighting potential links between lipid composition and drug resistance mechanisms. Results: Our results show distinct alterations in lipid composition associated with drug resistance. Specifically, drug-resistant strains exhibited reduced levels of phosphatidylcholine (PC) and phosphatidylglycerol (PG), particularly in the amphotericin B-resistant strain LiAmB1000.1. Sterol and glycerolipid species, including cholesteryl ester (CE) and triacylglycerol (TG) were also found to be diminished in LiAmB1000.1. These changes suggest significant lipid remodeling under drug pressure, potentially altering the biophysical properties of EV membranes and their capacity for molecule transfer. Furthermore, the lipidomic profiles of EVs from the other resistant strains, LiSb2000.1 and LiMF200.5, also displayed unique alterations, underscoring strain-specific adaptations to different drug resistance mechanisms. Conclusions: These significant alterations in lipid composition suggest potential lipid-based mechanisms underlying drug resistance in Leishmania, providing new avenues for therapeutic intervention.

Impact of Mycobacterium tuberculosis H37Rv Infection on Extracellular Vesicle Cargo in Macrophages: Implications for Host–Pathogen Interaction

Tuberculosis (TB) is one of the most common respiratory infections worldwide, and it is caused by Mycobacterium tuberculosis (Mtb). Mtb employs immune evasion mechanisms that allow the disease to become chronic. Despite extensive research, the host–pathogen interaction remains incompletely understood. Extracellular vesicles (EVs) are small membrane particles that play a regulatory role in infectious diseases. Host-derived EVs have been identified as carriers of proteins, messenger RNA, and lipids from both the host cells and the pathogens. In this study, we assessed the cargo of EVs in human macrophages infected with the virulent strain H37Rv of Mtb at 1 and 24 h post-infection (hpi). The results showed that 1 hpi, infected macrophages secreted EVs containing Mtb proteins (15 to 37 kDa) and Ag85 kDa, as well as RNA transcripts (ESAT-6, 5KST, Ag85, IS6110, 30 kDa, 19 kDa, and MPT64). However, these decreased at 24 hpi. The infection of macrophages with Mtb was observed to result in the release of EVs containing Ag85 protein and RNA transcripts of Mtb; this process appeared to diminish after 24 hpi, suggesting the existence of an evasion mechanism. Both Ag85 and the RNA transcripts could be potential biomarkers for the diagnosis of TB patients.

Analysis of free-living seabirds from Brazil as potential hosts of Toxoplasma gondii and serological investigation for antibodies against Leptospira spp.

Dispersal patterns of zoonotic pathogens can be strongly influenced by mobility and contact among hosts. Toxoplasma gondii infection has been documented in many avian species, however, there is little information regarding free-living seabird populations. Leptospira can infect domestic and wild animals, with birds being potential carriers of the bacteria. The continental shelf of the southwestern Atlantic Ocean is a foraging area for seabirds that breed locally, as well as migratory seabirds wintering in the area, which may come into contact with each other in prey aggregation areas and contribute to T. gondii and Leptospira spread. Therefore, this study aimed to investigate the prevalence of two important zoonotic pathogens in free-living seabirds. Blood samples were collected from 322 birds of three local breeders (Phaethon aethereus, Sula leucogaster and S. dactylatra) in the eastern coast of Brazil (Abrolhos Archipelago), and two migratory species using the area during the pre-laying (Pterodroma arminjoniana) and the non-breeding periods (Thalassarche chlororhynchos). Serological agglutination tests for detection of anti-Toxoplasma gondii and anti-Leptospira spp. antibodies were performed. None of the seabirds in this study was seroreactive to Leptospira spp., whereas 34.5% (n = 111) of the animals presented antibodies anti-T. gondii. Antibody titers in seropositive birds ranged from 10 to 640. There were seropositive birds in all sampled localities. This study provides the first records for P. arminjoniana and T. chlororhynchos as seropositive to T. gondii, suggesting their potential role as sentinels for the environmental contamination by T. gondii and also T. gondii infection. These findings indicate the circulation of the parasite in the Brazilian coastal and oceanic regions, probably due to the ingestion of T. gondii oocysts by birds, the epidemiological involvement of migratory birds as hosts of pathogens, as well as the role of the historical introduction of invasive vertebrates on Brazilian islands. Therefore, due to the serological evidence of infection, the dynamics of toxoplasmosis in seabirds, regarding their susceptibility towards the disease and the possible anthropogenic influence need to be better understood for the colonies to be included in the wildlife cycle of T. gondii.

Host-Pathogen Interactions in Mycobacterium tuberculosis: Molecular Mechanisms and Implications for Treatment

Worldwide, tuberculosis (TB) due to Mycobacterium tuberculosis is a major public health problem with high morbidity and mortality. This review reviewed the molecular mechanisms and their implications for treatment of M. tuberculosis infection, as well as the complex host pathogen interactions underpinning M. tuberculosis infection. The ability of the pathogen to avoid the host immune responses by utilizing critical strategies for the evasion, for instance, inhibition of phagosome-lyosome fusion and modulation of the host cell pathways are discussed first. T cells play a critical role in the adaptive immune response, and granulomas develop, which are then examined in detail. It importantly informs current treatment protocols which struggle to overcome issues of patient compliance, drug resistance and toxicity. Explored are novel therapeutic approaches targeting bacterial cell wall synthesis, virulence factors and the use of host directed therapies. Recent advances in the development of vaccines, including the innovative endeavors that hope to improve or replace the BCG vaccine, are also reviewed. The review ends by anticipating future directions in TB management, which could be facilitated through efforts related to personalized medicine, and combination therapies, as well as rapid diagnostics to change how we think about treatment. The insights from this study are important for developing novel strategies to fight TB and to bring down its burden globally.

ChIP-seq and structural analyses delineating the regulatory mechanism of master regulator EsrB in Edwardsiella piscicida.

As a crucial virulence regulator, EsrB possesses a LuxR-like superfamily domain at the C-terminal, which is conserved within the canonical NarL family regulators. Due to its critically important role in virulence and pathogenicity in fish hosts, the DNA binding ability has been believed to allow EsrB to regulate genes associated with the invasion process of host cells and basal metabolism in response to environmental stimuli. The lack of EsrB's crystal structure has been a major obstacle in understanding the molecular mechanisms of EsrB-DNA interaction which choreographs EsrB-mediated pathogenic behavior. Here, we conducted ChIP-seq and solved the crystal structure of the C-terminal of EsrB (EsrBC) at 2.20-Å resolution, which revealed that EsrB preferred to bind to virulence-associated promoters with a distinct 7'-4-7' pseudopalindromic DNA motif and interacted with metabolic-related promoters with a high AT DNA motif in Dulbecco's Modified Eagle's Medium (DMEM) (mimicking in vivo environments). Our results facilitate a detailed understanding of EsrB's regulatory role in Edwardsiella piscicida pathogenesis and expand our knowledge of virulence regulators in the family Hafniaceae.

Pattern Recognition Receptors in Periodontal Disease: Molecular Mechanisms, Signaling Pathways, and Therapeutic Implications

Periodontal disease remains a significant global health concern, characterized by complex host–pathogen interactions leading to tissue destruction. This review explored the role of pattern recognition receptors (PRRs) in the pathogenesis of periodontal disease, synthesizing current knowledge on their molecular mechanisms and potential as therapeutic targets. We examined the diverse family of PRRs, focusing on toll-like receptors (TLRs) and NOD-like receptors (NLRs), elucidating their activation by periodontal pathogens and subsequent downstream signaling cascades. This review highlights the intricate interplay between PRR-mediated pathways, including NF-κB and MAPK signaling, and their impact on inflammatory responses and bone metabolism in periodontal tissues. We discussed the emerging concept of PRR crosstalk and its implications for periodontal homeostasis and disease progression. Furthermore, this review addressed the potential of PRR-targeted therapies, exploring both challenges and opportunities in translating molecular insights into clinical applications. By providing an overview of PRRs in periodontal health and disease, this review aims to stimulate future research directions and inform the development of novel diagnostic and therapeutic strategies in periodontology.

Assessment of Babesia ovis pathogenicity in goats: implications for transmission dynamics and host resistant.

Babesia ovis, commonly associated with ovine babesiosis, poses a significant threat to sheep health, often resulting in severe clinical manifestations and high mortality rates. However, the impact of B. ovis on goats has remained uncertain, prompting us to investigate its pathogenicity in caprine hosts. Experimental infections using B. ovis-infected blood inoculation and infected tick infestation, were conducted on spleen-intact (n=5) and splenectomized (n=5) goats. The experimental infection was performed using fresh blood obtained from a B. ovis-infected splenectomized sheep. One spleen-intact sheep served as a control for the experimental infection with B. ovis-infected Rhipicephalus bursa ticks. While all experimentally infected sheep (#501, #575) displayed severe clinical symptoms and high parasitemia, goats exhibited resistance, showing no significant clinical manifestations or sustained parasitemia. Notably, B. ovis was detected in two spleen-intact goats via nested PCR, prompting further investigation into their role as reservoirs for tick-borne transmission. These goats were then infested with Babesia spp.-free R. bursa larvae (0.1 gr) and adults (50 females and 50 males) for transstadial and transovarial transmission experiments respectively. Results indicated that chronically B. ovis-infected spleen-intact goats are not significant sources for maintaining the tick-borne transmission cycle of the parasite. These findings highlight the differential susceptibility of goats to B. ovis infection compared to sheep and their limited role as reservoirs for parasite transmission. Understanding the role of goats in B. ovis transmission and their resistance mechanisms can inform effective control measures and reduce economic losses in affected regions. Further research into caprine babesiosis and host immunological responses is essential to fully elucidate their possible role as reservoirs of the parasite, and underlying mechanisms of host susceptibility and parasite pathogenesis.