Pathogen Invasion Research Articles

Do white-footed mice, the main reservoir of the Lyme disease pathogen in the United States, clinically respond to the borrelial tenancy?

ABSTRACT As white-footed mice, Peromyscus leucopus , are considered the primary animal reservoir of Borreliella burgdorferi sensu stricto ( Bb ), the main agent of Lyme disease (LD) in the United States, these animals represent the most relevant model to study borrelial spirochetes in the context of their natural life cycle. Previous studies have consistently demonstrated that although white-footed mice respond immunologically to the invasion of the Lyme pathogen, P. leucopus adults do not develop a clinically detectable disease. This tolerance, which is common for mammalian reservoirs of different pathogens, contrasts with detrimental anti-borrelial responses of C3H mice, a widely used animal model of LD, which always result in a clinical manifestation (e.g., arthritis). The current investigation is a follow-up of our recent study that already showed a relative quiescence of the spleen transcriptome for Bb -infected white-footed mice compared to the infected C3H mice. In an effort to identify the mechanism behind this tolerance, in this study, we have evaluated an extensive list of hematological and biochemical parameters measured in white-footed mice after their 70-day-long borrelial infection. Despite missing reference intervals for Peromyscus mice, our sex- and age-matched uninfected controls allowed us to assess the blood and serum parameters. In addition, for our assessment, we also utilized behavioral, immunological, and histological analyses. Collectively, by using the metrics reported herein, the present results have demonstrated clinical unresponsiveness of P. leucopus mice to the borrelial infection, presenting no restriction to a long-term host–pathogen co-existence.

Photosynthesis Responses to the Infection with Plant Pathogens

Photosynthesis, the remarkable process by which green plants synthesize nutrients using light energy, plays a crucial role in sustaining life on Earth. However, the effects of pathogens on photosynthesis are not widely understood. In general, a reduction of photosynthesis occurs upon the infection with pathogens. Two main scenarios are responsible for the reduction in photosynthetic capacity. In the first scenario, the pathogen attacks green aerial tissues such as caused by fungal and bacterial leaf spots and blights which affect photosynthesis by destroying green leaf tissue or causing defoliation. This leads to a decrease in the photosynthetic area, ultimately reducing photosynthesis. Interestingly, even when the overall chlorophyll content of leaves is significantly reduced due to pathogen invasion, the remaining chlorophyll-containing leaf area may maintain or even enhance its photosynthetic efficiency. This compensatory mechanism helps mitigate the loss of photosynthetic area. However, the overall yield of the plant is still affected. The second scenario is a reduction in chlorophyll content due to chlorosis, which is characterized by yellowing of leaves. It is a common symptom of plant diseases. It refers to a reduction in the amount of chlorophyll per chloroplast, rather than a decrease in chloroplast number. Diseases caused by viruses and phytoplasmas often exhibit chlorosis. While pathogens disrupt photosynthesis, plants exhibit significant adaptations to cope with these challenges. Understanding these interactions is essential for sustainable agriculture and ecosystem health. Thus, in this review, we discuss the effect of several pathogens on the photosynthesis processes and efficiency in detail.

Nucleus‐Targeting Photosensitizers Enhance Neutrophil Extracellular Traps for Efficient Eradication of Multidrug‐Resistant Bacterial Infections

AbstractNeutrophil extracellular traps (NETs) are web‐like complexes of DNA and proteins that are extruded by activated neutrophils and play critical roles as major components of the innate immune response against pathogen invasion. However, some microbes have developed strategies to evade NET attacks, leading to impaired immune defenses and persistent infections. In this study, an engineered neutrophil strategy for enhancing the antibacterial activity of NETs is developed. A nucleus‐targeting photosensitizer (NCP) with strong reactive oxygen species production and a strong DNA‐binding capacity is synthesized. NCP‐loaded neutrophils are subsequently constructed via direct incubation of NCP with neutrophils, and the NCP is closely inserted into the nucleus DNA. Upon activation by bacteria‐related toxins, NCP‐coupled NETs can be released rapidly, actively trapping bacteria and providing a high local concentration of NCP around them. Both in vitro and in vivo results revealed that NCP‐coupled NETs can effectively eradicate various multidrug‐resistant bacteria and biofilms through photodynamic therapy, overcome bacterial immune evasion, and promote tissue recovery from severe wound infections. This design can significantly strengthen NET function, providing a non‐antibiotic alternative platform for treating bacterial infectious diseases.

The diagnostic role of Lactobacillus spp. as representatives of the normal microbiome of the lower urogenital tract

Currently, scientific knowledge about various Lactobacillus species, which are representatives of the resident flora of the vagina, is actively expanding. We know, lactobacilli are an integral part of the female genital tract. Currently, about 20 different types of lactobacilli are known. Most of the lactobacilli already studied contribute to maintaining vaginal health by providing protection from pathogenic microorganisms, the development of dysbiosis, pregnancy complications, including premature birth. The protective function is provided primarily by the formation of Dand L-forms of lactic acid, which maintains an optimal acidic pH, from the glycogen of the vaginal epithelium. Lactobacillus spp. also prevent adhesion and invasion of pathogens into epithelial cells, synthesize bacteriocins, and inhibit the release of proinflammatory cytokines. However, to date, there is already evidence that not all representatives of lactobacilli have a positive effect on the health of the female body. Thus, patients with the CSTIII morphotype, dominated by L. iners, are especially predisposed to the development of vaginal dysbiosis, and the dominance of L. acidophilus in patients is probably associated with infertility. Currently, there is no reliable evidence of the positive and/or negative effects of many lactobacilli on the female body, and existing studies on a number of bacteria are limited and contradictory. In this regard, it is relevant to further study the characteristics and properties of Lactobacillus spp., colonizing the vagina, for a more accurate understanding of the role of lactobacilli in the vagina and the application of the knowledge gained in clinical practice for the treatment and prevention of various disorders of the normal vaginal microbiome.

14-3-3ε conditional knockout mice exhibit defects in the development of the epidermis.

The epidermis is a stratified epithelium that functions as the first line of defense against pathogenic invasion and acts as a barrier preventing water loss. In this study, we aimed to decipher the role of 14-3-3ε in the development of the epidermis. We report that loss of 14-3-3ε in the epidermis of juvenile and adult mice reduces cell division in the basal layer and increases the percentage of cells with multiple centrosomes, leading to a reduction in the thickness of the basal and stratified layers. We also demonstrate a decrease in the expression of differentiation markers, although no gross morphological defects in the skin or adverse effects on the survival of the mice were observed. These results suggest that loss of 14-3-3ε in the epidermis may lead to defects in proliferation and differentiation.

Linking symbioses with intrinsic chemical defences in conifers: Fungal‐mediated resistance against an invasive pathogen

Abstract Invasive pathogens threaten the sustainability of forest ecosystems globally. Trees possess intrinsic pathogen defence mechanisms, including major gene resistance (MGR) and quantitative disease resistance (QDR). Plant‐symbiotic fungi can enhance tree defences, generating far‐reaching ecosystem impacts. However, the specific contributions of various fungal guilds to this symbiont‐mediated resistance remain unclear. In this study, we inoculated six Pinus monticola seedling families exhibiting resistance (MGR or QDR) or high susceptibility to the introduced invasive pathogen Cronartium ribicola, the causative agent of white pine blister rust (WPBR), with endophytic and ectomycorrhizal fungi, either alone or in combination (symbiont treatments), in an open‐air greenhouse study. Over a period of 25 months, we monitored the growth, foliar terpene defences, and disease progression in trees before and after C. ribicola infection and in trees inoculated with the symbionts but never inoculated with C. ribicola. We observed enhanced inducible host defences and evidence of defensive priming in response to symbiont treatments. In WPBR‐free control treatments, differences in pine defences coincided with an increased seedling growth rate. For WPBR‐infected seedlings, symbiont treatments reduced disease symptoms in seedlings with QDR and to a lesser extent in susceptible families, but not in those with MGR. Furthermore, disease symptoms correlated with variations in terpene composition. Synthesis and applications: Interactions with fungal symbionts should be considered when breeding native trees for resistance against invasive pathogens. Our study underscores the capacity of endophytic and ectomycorrhizal fungi to enhance tree growth and defence while also reducing disease symptoms. We also show that fungi can induce long‐lasting changes in conifer foliar terpenes, suggesting potential applications in tree protection from invasive pathogens.

Whole-Genome Sequencing Reveals the Population Structure and Genetic Diversity of Salmonella Typhimurium ST34 and ST19 Lineages.

Salmonella Typhimurium is an invasive gastrointestinal pathogen for both humans and animals. To investigate the genetic framework and diversity of S. Typhimurium, a total of 194 S. Typhimurium isolates were collected from patients in a tertiary hospital between 2020 and 2021. Antimicrobial susceptibility testing was used to confirm the resistance phenotype. Whole-genome sequencing and bioinformatics analysis were performed to determine the sequence type, phylogenetic relationships, resistance gene profiles, Salmonella pathogenicity island (SPI) and the diversity of the core and pan genome. The result showed that 57.22% of S. Typhimurium isolates were multidrug resistant and resistance of total isolates to the first-line drug ciprofloxacin was identified in 60.82%. The population structure of S. Typhimurium was categorized into three lineages: ST19 (20.10%, 39/194), ST34-1 (47.42%, 92/194) and ST34-2 (40.65%, 63/194), with the population size exhibiting increasing trends. All lineages harbored variety of fimbrial operons, prophages, SPIs and effectors that contributed to the virulence and long-term infections of S. Typhimurium. Importantly, ST34-1 lineage might potentially be more invasive due to the possession of SPI1-effector gene sopE which was essential for the proliferation, internalization and intracellular presence of S. Typhimurium in hosts. Multiple antimicrobial resistance genes were characteristically distributed across three lineages, especially carbapenem genes only detected in ST34-1&2 lineages. The distinct functional categories of pan genome among three lineages were observed in metabolism, signaling and gene information processing. This study provides a theoretical foundation for the evolved adaptation and genetic diversity of S. Typhimurium ST19 and ST34, among which ST34 lineages with multidrug resistance and potential hypervirulence need to pay more attention to epidemiological surveillance.

The vector regulation hypothesis: dynamic competition between pathogen and vector behaviors constrains Xylella fastidiosa biofilm development in sharpshooter foreguts.

Xylella fastidiosa (Xf) bacteria form biofilm on the cuticular surfaces of the functional foregut (precibarium and cibarium) of its vectors, xylem fluid-ingesting sharpshooter leafhoppers and spittlebugs. While much is known about Xf biofilm development and maturation in vitro, little is known about these processes in vectors. Real-time (RT)-PCR was used to quantify Xf genomes daily in the functional foreguts of blue-green sharpshooters, Graphocephala atropunctata, over 7 days of exposure to infected grapevines. Scanning electron microscopy (SEM) was used to examine Xf biofilm formation at 4 and 7 days of that time course. PCR showed populations building and reducing over a 4-day cycle. SEM revealed that foreguts at 4 days showed variability in quantity and location of bacterial attachment. Only early-stage biofilm formation occurred in low-turbulence areas of the cibarium, while high-turbulence areas of the cibarium and precibarium had rare but older, more developed macro-colonies. Biofilm was almost absent at 7 days but left behind adhesive material and remnants of prior colonization. Evidence supports the hypothesis that bacterial colonization was repeatedly interrupted and constrained by the vector. Behaviors such as egestion and enzymatic salivation likely can loosen and eject Xf biofilm, perhaps when profuse biofilm interferes with ingestion. Thus, vector acquisition of Xf is a dynamic and stochastic process of interactions between bacteria and insects. We further hypothesize for future testing that the insect can regulate this interaction. A deep understanding of Xf acquisition will aid the ongoing development of grapevine resistance to vector transmission of xylellae diseases.IMPORTANCEXylella fastidiosa (Xf) is one of the most destructive invasive plant pathogens in the world, able to hijack new vectors when it invades a region; yet the temporal interplay of bacterial colonization and insect behavior is unknown. This paper describes important findings about the process of Xf biofilm formation and maturation in a vector, contrasting similarities and differences with such formation in vitro. Results support the hypothesis that the behavior of the vector constrains and may regulate Xf biofilm formation, in dynamic competition with the bacterium. The data from this paper partly explain why Xf is so successful at invasion. Because the bacterium can be acquired and inoculated very quickly, it can move readily from old to new vectors and host plants in all-new environments. Our findings are relevant to biosecurity decisions because they demonstrate the importance of identifying potential vector species in the Xylella invasion front.

Effects of phosphorylation on CsTT12 transport function: Acomparative phosphoproteomic analysis of flavonoid biosynthesis in tea plants (Camellia sinensis).

Monomeric flavan-3-ols and their oligomeric forms, proanthocyanidins (PAs), are closely related to the bitterness of tea beverages. Monomeric flavan-3-ols are characteristic flavor compounds in tea. Increasing the content of PAs and anthocyanins enhances the resistance of tea plants to pathogen invasion but decreases the quality of tea beverages. MATE family transporters play a critical role in transferring monomeric flavan-3-ols and anthocyanins into vacuoles for storage or subsequent condensation into PAs. Their activities modulate the ratio of monomeric flavan-3-ols to PAs and increase anthocyanin content in tea plants. In this study, it was observed that the gene expression and protein phosphorylation level of the MATE transporter CsTT12, a vacuole-localized flavonoid transporter, were notably upregulated following exogenous sucrose treatment, promoting PA synthesis in tea plants. Further analysis revealed that overexpression of CsTT12 and CsTT12S17D significantly increased the content of anthocyanins and PAs in plants, whereas CsTT12S17A did not. In CsTT12 knockdown plants, PA's accumulation decreased significantly, while monomeric catechin content increased. Moreover, phosphorylation modification enhanced the vacuolar membrane localization of CsTT12, whereas dephosphorylation weakened its vacuolar membrane localization. This study uncovers the crucial role of phosphorylation in flavonoid biosynthesis and provides insights into balancing quality improvements and resistance enhancement.

Functional characterization of peroxiredoxin 5 from yellowtail clownfish (Amphiprion clarkii): immunological expression assessment, antioxidant activities, heavy metal detoxification, and nitrosative stress mitigation

Peroxiredoxin 5 (Prdx5) is the last recognized member of Prdx family. It is a unique, atypical, 2-Cys antioxidant enzyme, protecting cells from death caused by reactive oxygen species (ROS). In this study, the Prdx5 ortholog of Amphiprion clarkii (AcPrdx5) was identified and characterized to explore its specific structural features and functional properties. The open reading frame of AcPrdx5 is 573 bp long and encodes 190 amino acids containing a mitochondrial targeting sequence, thioredoxin domain, and two conserved cysteine residues responsible for antioxidant function. The predicted molecular weight and theoretical isoelectric point of AcPrdx5 are 20.3 kDa and 9.01, respectively. AcPrdx5 sequences were found to be highly conserved across the other orthologs from various organisms and it distinctively clustered within the fish Prdx5 subclade of the phylogenetic tree. The expression of AcPrdx5 was ubiquitously detected among twelve tested tissues, with the highest level in the brain. Furthermore, the mRNA levels of AcPrdx5 in the blood and head-kidney tissues were significantly (p < 0.05) upregulated following polyinosinic-polycytidylic acid (Poly I:C), lipopolysaccharide (LPS), and Vibrio harveyi immune challenge. A concentration-dependent antioxidant potential of recombinant AcPrdx5 was observed in insulin disulfide bond reduction, heavy metal detoxification, free radical and hydrogen peroxide (H2O2) scavenging assays. Additionally, AcPrdx5 overexpression in fathead minnow (FHM) cells upregulated the antioxidant-associated gene (Rrm1, MAPK, SOD2, and PRDX1) expression after H2O2 treatment, and promoted cell viability upon arsenic (As) exposure. In macrophages, AcPrdx5 overexpression effectively suppressed substantial nitric oxide production under lipopolysaccharide treatment. Collectively, our results suggest that AcPrdx5 may play roles in both antioxidant defense system and innate immune response against pathogenic invasions in A. clarkii.

The role of TF-b in iron homeostasis and bacterial defense in common carp (Cyprinus carpio)

Transferrin (TF) is a prototypical biological macromolecule protein known for its iron-binding properties. TF proteins play a crucial role in modulating host iron homeostasis and defending against pathogen invasion. In this study, we utilized common carp (Cyprinus carpio) tissues and Epithelioma papulosum cyprinid (EPC) cells to establish experimental models of iron overload with FeCl3 or ferric amine citrate (FAC), and to establish experimental models of bacterial infection with Aeromonas hydrophila. The current research has successfully identified the CcTF-b gene in common carp, revealing an ORF of 2001 bp with N-terminal and C-terminal structures. CcTF-b exhibited inhibitory effects on the growth of LPS and LTA in vitro. In the experimental models, the upregulations of PTGS2a and PTGS2a-like mRNA and protein levels were observed. Overexpression or interference with CcTF-b levels can modulate the expression of ferroptosis-related genes, inflammatory cytokines, lipid reactive oxygen species, GSH/GSSH levels, and Fe2+ concentration. Significantly, the expression levels of Nrf2 and GPX4 mRNA and protein, as well as the bacterial load of A. hydrophila, could be also modulated either by upregulating or downregulating CcTF-b factors. In conclusion, in this study, these findings suggest that CcTF-b plays a critical role in the innate immune response of common carp.

A Standardized Mouse Model for Wound Infection with Pseudomonas aeruginosa

Pseudomonas aeruginosa is a highly drug-resistant pathogen known to impair wound healing and provoke inflammatory responses, potentially leading to immune dysregulation. This study aimed to systematically investigate the immune response mechanisms mediated by cytokines following P. aeruginosa infection through the development of a standardized wound model. Kunming mice were selected as experimental subjects and given 8 mm diameter lesions on their backs and inoculated with standard strains PAO1 and PA14. The key parameters assessed included changes in body weight, wound redness and swelling, bacterial dynamics, protein content in wound tissues, immune responses, and pathological alterations. The results demonstrated that pathogen invasion significantly inhibited wound healing, with healing rates in the infected groups (87.5 ± 6.3% and 77.1 ± 3.6%) being notably lower than those in the uninfected control group. P. aeruginosa persisted in the wounds for up to 12 days, with bacterial loads decreasing from 8 log to 2 log. Additionally, there was a marked reduction in the protein content of the wound tissue and an increase in the expression levels of inflammatory factors such as IL-1β and TNF-α. The thickness of granulation tissue and the number of neovessels were significantly lower compared to the uninfected control group. This study establishes a standardized paradigm for creating a mouse model of P. aeruginosa infection in wounds, emphasizing the importance of appropriate mouse strains, uniform wound preparation methods, and moderate inoculation doses for reliable and accurate experimental results. These elements will facilitate the assessment of changes across six key indicators post-infection, providing a foundational data set and technical support for future mechanistic investigations of P. aeruginosa infection and the development of targeted antimicrobial strategies.

Leishmania protein KMP-11 modulates cholesterol transport and membrane fluidity to facilitate host cell invasion.

The first step of successful infection by any intracellular pathogen relies on its ability to invade its host cell membrane. However, the detailed structural and molecular understanding underlying lipid membrane modification during pathogenic invasion remains unclear. In this study, we show that a specific Leishmania donovani (LD) protein, KMP-11, forms oligomers that bridge LD and host macrophage (MΦ) membranes. This KMP-11 induced interaction between LD and MΦ depends on the variations in cholesterol (CHOL) and ergosterol (ERG) contents in their respective membranes. These variations are crucial for the subsequent steps of invasion, including (a) the initial attachment, (b) CHOL transport from MΦ to LD, and (c) detachment of LD from the initial point of contact through a liquid ordered (Lo) to liquid disordered (Ld) membrane-phase transition. To validate the importance of KMP-11, we generate KMP-11 depleted LD, which failed to attach and invade host MΦ. Through tryptophan-scanning mutagenesis and synthesized peptides, we develop a generalized mathematical model, which demonstrates that the hydrophobic moment and the symmetry sequence code at the membrane interacting protein domain are key factors in facilitating the membrane phase transition and, consequently, the host cell infection process by Leishmania parasites.

Single-cell analysis of nasal epithelial cell development in domestic pigs

The nasal mucosa forms a critical barrier against the invasion of respiratory pathogens. Composed of a heterogeneous assortment of cell types, the nasal mucosa relies on the unique characteristics and complex intercellular dynamics of these cells to maintain their structural integrity and functional efficacy. In this study, single-cell RNA sequencing (scRNA-seq) of porcine nasal mucosa was performed, and nineteen distinct nasal cell types, including nine epithelial cell types, five stromal cell types, and five immune cell types, were identified. The distribution patterns of three representative types of epithelial cells (basal cells, goblet cells, and ciliated cells) were subsequently detected by immunofluorescence. We conducted a comparative analysis of these data with published human single-cell data, revealing consistent differentiation trajectories among porcine and human nasal epithelial cells. Specifically, basal cells serve as the initial stage in the differentiation process of nasal epithelial cells, which then epithelial cells. This research not only enhances our understanding of the composition and transcriptional signature of porcine nasal mucosal cells but also offers a theoretical foundation for developing alternative models for human respiratory diseases.

Research progress on V delta 1+ T cells and their effect on pathogen infection.

The ongoing high occurrence of harmful infectious diseases significantly threatens human health. Existing methods used to control such diseases primarily involve targeting the pathogens, usually neglecting the vital role of host factors in disease advancement. Gamma delta (γδ) T cells act as a bridge between innate and adaptive immunity, playing a crucial role in combating pathogen invasion. Among these γδT cell subsets, which are categorized based on T cell receptor delta variable expression patterns, V delta (δ) 1+ T cells possess unique recognition abilities and regulatory characteristics and actively engage in various immune responses. The differentiation, development, and immune reactivity of Vδ1+ T cells are closely associated with the initial and progressive stages of infectious diseases. This article provides an overview of the classification, distribution, differentiation, and development of Vδ1+ T cells and their mechanisms in combating pathogenic infections, offering new insights for disease diagnosis and treatment.

Porcine Nose Atrophy Assessed by Automatic Imaging and Detection of Bordetella bronchiseptica and Other Respiratory Pathogens in Lung and Nose

The nasal mucosa is a crucial filtering organ to prevent attachment and invasion of pathogens. To assess nasal health in relation to lung health, transverse cross sections of the nasal turbinates of 121 pigs suffering from respiratory disease and sent for diagnostic necropsy were scored visually and by an artificial intelligence (AI) medical diagnostic application (AI DIAGNOS), resulting in a high correlation of both scores (p &lt; 0.001). Nasal samples of the diseased pigs were examined only for Bordetella (B.) bronchiseptica (PCR and bacteriological culture) and Pasteurella (P.) multocida (bacteriological culture). All pigs showed various degrees of inflammatory lung tissue alterations, and 35.5% of the pigs had atrophy of the nasal turbinates with no relation to detection rates of B. bronchiseptica (54.5%) and P. multocida (29.0%) in the nose. All P. multocida strains from nose samples were negative for the toxA gene so non-progressive atrophic rhinitis was diagnosed. Pigs positive for B. bronchiseptica in the nose were more often positive for B. bronchiseptica in the lung (p &lt; 0.001) and for other bacterial species in the lower respiratory tract (p = 0.005). The new diagnostic application for scoring cross sections of nasal turbinates is a valuable tool for a fast and reproducible diagnostic.

Experimental evidence of negative agricultural impacts and effectiveness of mitigation strategies of invasive green iguanas (Iguana iguana) in Puerto Rico

Losses in crop yield due to invasive insects, weeds, pathogens, and herbivores cost trillions of dollars per year globally. To prevent further spread of invasive agricultural pest species, continuous monitoring and prevention are crucial. Once introduced, however, assessing the impact of an invasive pest on agricultural production and testing management strategies are essential. The green iguana (Iguana iguana), a globally widespread invasive herbivore, is considered a possible agricultural pest although no quantitative data on its impact are available. In this study, we evaluated the impact of the invasive green iguana on cucumber (Cucumis sativus, var. Dasher II) and lettuce (Lactuca sativa, var. Black-seeded Simpson) yield by testing the efficacy of two management strategies – Neem-based pesticide and mesh fencing – compared to open field cultivation in Puerto Rico. Mesh fencing led to 20% more growth and doubled cucumber yield compared to open field cultivation, while spraying Neem led to an 18% increase in plant growth but no effect on cucumber yield. We found no difference in lettuce growth or yield among treatment and control plots. This study supports categorizing the green iguana as an invasive agricultural pest species and demonstrates the reptile’s potential to reduce crop yield. It also shows that Neem application at the manufacturer’s suggested concentration is not an effective mitigation technique for reducing crop loss due to green iguana herbivory. Government agencies in regions where the green iguana has the potential to be introduced should consider the species a threat to food production when developing monitoring programs and drafting regulations.

The arginine/ornithine binding protein ArgT plays an essential role in Brucella neotomae/Brucella melitensis to prevent intracellular killing and contribute to chronic persistence in the host

ABSTRACT Brucella species are facultative intracellular bacterial pathogens that cause the contagious zoonotic disease, brucellosis. Brucella spp. infect a wide range of animals, including livestock, wild animals, and marine mammals. Compared with other invasive bacterial pathogens, partial information is available on the virulence factors of Brucella that enable them to survive in the host. Here, we performed transposon-based random mutagenesis of B. neotomae and identified the arginine/ornithine binding protein, ArgT, as one of the crucial virulence determinants of Brucella. Deleting ArgT from B. neotomae or B. melitensis resulted in its attenuation in macrophages, which was restored upon complementation with an ArgT expression plasmid. We observed that macrophages infected with ΔArgT-B. neotomae produced elevated levels of NO due to the inability of these mutants to deplete the host intracellular arginine through their importer. Furthermore, defective survival of ΔArgT B. neotomae and B. melitensis was observed in the infected mice, which correlated with enhanced NO production in the mice. Our studies revealed that ArgT plays a vital role in preventing intracellular killing and contributes to the chronic persistence of B. neotomae/B. melitensis in the host. This study highlights the essential role of arginine in clearing intracellular infections and the subversion of this host defence mechanism by intracellular pathogens for their chronic persistence.

The Staphylococcus aureus-antagonizing human nasal commensal Staphylococcus lugdunensis depends on siderophore piracy

BackgroundBacterial pathogens such as Staphylococcus aureus colonize body surfaces of part of the human population, which represents a critical risk factor for skin disorders and invasive infections. However, such pathogens do not belong to the human core microbiomes. Beneficial commensal bacteria can often prevent the invasion and persistence of such pathogens by using molecular strategies that are only superficially understood. We recently reported that the commensal bacterium Staphylococcus lugdunensis produces the novel antibiotic lugdunin, which eradicates S. aureus from the nasal microbiomes of hospitalized patients. However, it has remained unclear if S. lugdunensis may affect S. aureus carriage in the general population and which external factors might promote S. lugdunensis carriage to enhance its S. aureus-eliminating capacity.ResultsWe could cultivate S. lugdunensis from the noses of 6.3% of healthy human volunteers. In addition, S. lugdunensis DNA could be identified in metagenomes of many culture-negative nasal samples indicating that cultivation success depends on a specific bacterial threshold density. Healthy S. lugdunensis carriers had a 5.2-fold lower propensity to be colonized by S. aureus indicating that lugdunin can eliminate S. aureus also in healthy humans. S. lugdunensis-positive microbiomes were dominated by either Staphylococcus epidermidis, Corynebacterium species, or Dolosigranulum pigrum. These and further bacterial commensals, whose abundance was positively associated with S. lugdunensis, promoted S. lugdunensis growth in co-culture. Such mutualistic interactions depended on the production of iron-scavenging siderophores by supportive commensals and on the capacity of S. lugdunensis to import siderophores.EJt4aqYa_PFzdC4ihACHg3Video ConclusionsThese findings underscore the importance of microbiome homeostasis for eliminating pathogen colonization. Elucidating mechanisms that drive microbiome interactions will become crucial for microbiome-precision editing approaches.

Induced Resistance in Fruit and Vegetable Enhancing Host Defence to Curve Post-harvest Diseases

Induced resistance (IR) is an emerging, environmentally friendly strategy to manage post-harvest diseases in fruits and vegetables by enhancing the plant’s innate immune system. This approach leverages the plant's natural defense mechanisms, including the activation of defense-related enzymes like chitinases, glucanases, and peroxidases, accumulation of secondary metabolites such as phytoalexins and phenolics, and the strengthening of cell walls to prevent pathogen invasion. Additionally, the production of reactive oxygen species (ROS) plays a crucial role in both signaling and direct pathogen inhibition. Despite its potential, the effectiveness of IR varies across different crops and pathogens, and its success is heavily influenced by environmental factors, such as humidity, temperature, and light. There are also concerns regarding possible trade-offs, such as reduced yield or changes in fruit quality due to the diversion of energy towards defense responses. However, the integration of IR with other disease management strategies, including the use of biological control agents and conventional fungicides, has shown promising results in reducing post-harvest losses. Case studies in fruits like apples, tomatoes, and citrus, as well as vegetables like potatoes and peppers, demonstrate the practical applications of IR in commercial agriculture. Advances in genetic engineering are opening new pathways for enhancing IR by manipulating key genes involved in defense pathways, while new formulations and precision agriculture technologies offer greater control and efficiency in IR applications. These innovations, along with optimized post-harvest handling and storage practices, hold the potential to make IR a more reliable and sustainable solution for managing post-harvest diseases. However, ongoing research is necessary to address the variability in effectiveness and to explore long-term sustainability, especially as pathogens evolve and environmental conditions change. Induced resistance, when integrated with a comprehensive disease management approach, offers a significant step forward in reducing post-harvest losses and improving food security globally.