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At least 91 records · Page 5

Abiotic Versus Biotic Pathogens: Replicative Growth in Host Tissues Key to Discriminating Between Biotoxic Injury and Active Pathogenesis

Life can be defined as a self-sustaining chemical system capable of undergoing Darwinian evolution; a self-bounded, self-replicating, and self-perpetuating entity [1]. This definition should hold for terrestrial as well as extraterrestrial life-forms. Although, it is reasonable to expect that a Mars life-form would be more adaptable to Mars-like conditions than to Earth-like environments, it remains possible that negative ecological or host interactions might occur if Mars microbiota were to be inadvertently released into the terrestrial environment. A biogenic infectious agent can be defined as a self-sustaining chemical system capable of undergoing Darwinian evolution and derives its sustenance from a living cell or from the by-products of cell death. Disease can be de-fined as the detrimental alteration of one or more ordered metabolic processes in a living host caused by the continued irritation of a primary causal factor or factors; disease is a dynamic process [2]. In contrast, an injury is due to an instantaneous event; injury is not a dynamic process [2]. A causal agent of disease is defined as a pathogen, and can be either abiotic or biotic in nature. Diseases incited by biotic pathogens are the exceptions, not the norms, in terrestrial host-microbe interactions. Disease induction in a plant host can be conceptually characterized using the Disease Triangle (Fig. 1) in which disease occurs only when all host, pathogen, and environ-mental factors that contribute to the development of disease are within conducive ranges for a necessary minimum period of time. For example, plant infection and disease caused by the wheat leaf rust fungus, Puccinia recondita, occur only if virulent spores adhere to genetically susceptible host tissues for at least 4-6 hours under favorable conditions of temperature and moisture [3]. As long as one or more conditions required for disease initiation are not available, disease symptoms will not develop.

Schuerger, Andrew C.↗

Effects of Simulated Microgravity on a Host-Pathogen System

While it has been shown that decades of astronauts and cosmonauts can suffer from illnesses both during and after spaceflight, the underlying causes are still poorly understood, due in part to the fact that there are so many variables to consider when investigating the human immune system in a complex environment. Invertebrates have become popular models for studying human disease because they are cheap, highly amenable to experimental manipulation, and have innate immune systems with a high genetic similarity to humans. Fruit flies (Drosophila melanogaster) have been shown to experience a dramatic shift in immune gene expression following spaceflight, but are still able to fight off infections when exposed to bacteria. However, the common bacterial pathogen Serratia marcescens was shown to become more lethal to fruit flies after being cultured in space, suggesting that not only do we need to consider host changes in susceptibility, but also changes in the pathogen itself after spaceflight conditions. Being able to simulate spaceflight conditions in a controlled environment on the ground gives us the ability to not only evaluate the effects of microgravity on the host immune system, but also how the microorganisms that cause immune disorders are being affected by these drastic environmental shifts. In this study, I use a ground-based simulated microgravity environment to examine the genetic changes associated with increased S. marcescens virulence in order to understand how microgravity is affecting this pathogen, as well as how these genetic changes influence and interact with the host immune system. This study will provide us with more directed approaches to studying the effects of spaceflight on human beings, with the ultimate goal of being able to counteract immune dysfunction in future space exploration.

Immunology↗

Gene Expression of Pathogens in Simulated Microgravity

Extended exposure to radiation and microgravity in space has been linked to astronauts developing chronic diseases upon returning to Earth. The Gram-negative pathogen Serratia marcescens has been shown to potentially cause significant infections in humans and in insect models on Earth. Our recent findings also showed that S. marcescens shows an increase in virulence after a short period of growth in the spaceflight environment, which raises initiatives to find the correlation between space environment and the increased virulence. Because we know that the health of astronauts is immunocompromised in space, it is possible that the combination of increased bacterial virulence and the weakened immune system will cause astronauts to be more susceptible to chronic diseases in extended spaceflight. With 75% of human disease genes being conserved in the fruit fly Drosophila melanogaster, these insects act as an ideal model organism to study the human immune system. The high accessibility, low cost, high rate of reproductivity, and short lifespans of D. melanogaster facilitate efficient, high-quality research that seeks to understand altered virulence of this opportunistic pathogen. In this ground-based study, we will use a rotating wall vessel apparatus to simulate microgravity and determine how pathogenicity changes by evaluating differences in gene expression for S. marcescens between bacteria grown in simulated microgravity conditions and controls. We will compare the results of our findings to gene expression patterns in actual spaceflight samples of S. marcescens grown on the ISS (International Space Station) during a recent validation mission, to see if there are common mechanisms across our simulated microgravity and actual spaceflight microgravity samples that both show increased virulence in the fruit fly. With extended space travel in the foreseeable future, understanding how human physiology will be affected by these different factors will help mitigate risks and deaths.

spaceflight analogue↗

Effects of Simulated Microgravity on a Host-Pathogen System

While it has been shown that decades of astronauts and cosmonauts suffer from immune disorders both during and after spaceflight, the underlying causes are still poorly understood, due in part to the fact that there are so many variables to consider when investigating the human immune system in a complex environment. Invertebrates have become popular models for studying human disease because they are cheap, highly amenable to experimental manipulation, and have innate immune systems with a high genetic similarity to humans. Fruit flies (Drosophila melanogaster) have been shown to experience a dramatic shift in immune gene expression following spaceflight, but are still able to fight off infections when exposed to bacteria. Furthermore, a recent spaceflight mission showed that flies are more susceptible to infection following exposure to microgravity conditions, compared to ground-reared flies from the same population. Additionally, the common bacterial pathogen Serratia marcescens was shown to become more lethal to fruit flies (both space- and ground-reared) after being cultured in space, suggesting that not only do we need to consider host changes in susceptibility, but also changes in the pathogen itself after spaceflight conditions. Being able to simulate spaceflight conditions in a controlled environment on the ground gives us the ability to not only evaluate the effects of microgravity on the host immune system, but also how the microorganisms that cause immune disorders are being affected by these drastic environmental shifts. In this study, I use both spaceflight and ground-based (simulated microgravity) environments to examine the genetic changes associated with increased S. marcescens virulence in order to understand how microgravity is affecting this pathogen, as well as to evaluate how these genetic changes influence and interact with the host immune system. This study will provide us with more directed approaches to studying the effects of spaceflight on human beings, with the ultimate goal of being able to ameliorate human immune dysfunction in future space exploration.

Immunology↗

Does Seed Sanitization Affect the Plant Rhizosphere Microbiome and Its Ability to Compete with the Human Associated Pathogen, E. coli on Salad Crops?

Cultivation of crops in controlled environmental agricultural systems may limit microbial colonization and reduce diversity of the microbial communities. Practices like seed and growth medium sanitization may further impact microbial communities in the mature plant and the plant’s capacity to limit the growth of pathogens through competition. As humans expand their travels to space, understanding plant growth, health, and development in closed environments will be critical to the success of producing a safe, supplemental food source for astronauts. To determine the persistence of a potential human pathogen in plant growth and development, sanitized and unsanitized seeds from, mizuna (Brassica rapa var japonica) and red romaine lettuce (Lactuca sativa cultivar ‘Outredgeous’), were inoculated with Escherichia coli, ATCC 21445, germinated under simulated International Space Station (ISS) environmental conditions and harvested every 7 days until maturity. The persistence of E. coli in the rhizosphere was determined by plating on selective media, real time PCR (Polymerase Chain Reaction) and community sequencing of the rhizosphere communities. E. coli was detected in the crops’ roots and leaves for several weeks post germination. At day 28, plants from sanitized seeds had significantly higher counts of E. coli on the roots than those from unsanitized seeds. E. coli was also detected on a few uninoculated plants indicating airborne cross contamination among plants in the same growth chamber and suggesting an influence of the natural microbiome on human pathogen survival and persistence in leafy greens. Sequencing analysis revealed variations in composition and diversity between the communities. Understanding the microbial community of the rhizospheric microbiome is only the first step in determining the relationships between plants. Additional studies to include genotypic and phenotypic variations in the plants should be considered to determine if the natural microbes in the rhizosphere may contribute to the health and therefore, safety of the edible plants.

Khodadad, Christina L. M.↗

Methods of identifying and modulating pathogen resistance in plants

Pathogenic fungi from the genus Sphaerulina cause damage to a diverse array of economically important plant species. The present disclosure provides methods of determining whether a plant is susceptible to pathogenic fungi infections. The disclosure further provides methods of engineering pathogenic fungi-resistant plants from susceptible plants using targeted genome editing techniques.

Muchero, Wellington↗

Agnostic capture of pathogens for the detection and diagnostics of emerging threats

The continued emergence of pathogens, whether novel, re-emerging, or engineered, poses a persistent global biosecurity and public health challenge. Recent outbreaks, including COVID-19, Lassa fever, Marburg virus, mpox, and avian influenza, underscore the urgent need for robust systems that enable rapid surveillance, early diagnosis, and timely countermeasures before widespread human transmission occurs. In this article, we focus on early detection technologies and systematically evaluate current diagnostic and sensing modalities. We highlight sequencing and spectroscopy as two complementary approaches capable of providing broad, agnostic detection and rich biological insight. Our analysis emphasizes that scientific innovation alone is insufficient: effective preparedness also requires improved data curation, integration, and sharing to build AI-ready resources that accelerate future responses. We argue for coordinated advances in both technological capabilities and supporting infrastructure to enable the rapid identification and characterization of emerging pathogens and to fully leverage modern science against evolving infectious threats.

Environmental health↗

Inactivation of multiple human pathogens by Fathhome's dry sanitizer device: Rapid and eco-friendly ozone-based disinfection

SARS-CoV-2 spread rapidly, causing millions of deaths across the globe. As a result, demand for medical supplies and personal protective equipment (PPE) surged and supplies dwindled. Separate entirely, hospital-acquired infections have become commonplace and challenging to treat. To explore the potential of novel sterilization techniques, this study evaluated the disinfection efficacy of Fathhome's ozone-based, dry-sanitizing device by dose and time response. Inactivation of human pathogens was tested on non-porous (plastic) surfaces. 95.42-100% inactivation was observed across all types of vegetative microorganisms and 27.36% inactivation of bacterial endospores tested, with no residual ozone detectable after completion. These results strongly support the hypothesis that Fathhome's commercial implementation of gas-based disinfection is suitable for rapid decontamination of a wide variety of pathogens on PPE and other industrially relevant materials.

59 BASIC BIOLOGICAL SCIENCES↗

Aeromonas in South Asia: genomic insights into an environmental pathogen and reservoir of antimicrobial resistance

Aeromonads are an ecologically versatile group of bacteria that cause infections in aquatic animals and are recognised as emerging human pathogens. Despite this, our understanding of Aeromonas diversity, especially the relationship between clinical and environmental strains, remains limited. Here, we present a genomic analysis of the Aeromonas genus, comprising 1853 genomes, and a detailed comparison of clinical and environmental strains from South Asia, including 996 newly sequenced genomes from Bangladesh and India. Phylogenetic analyses revealed that Aeromonas is a highly diverse genus, with no distinct clade separating clinical and environmental isolates. We identified 28 Aeromonas species and 905 novel sequence types, comprising 72.5% of the genomes. Notably, we show a high incidence of antimicrobial resistance (AMR) genes across all isolates, including against front and last-line antibiotics. Finally, we highlight frequent misidentification of Aeromonas as Vibrio cholerae, which is relevant to cholera-endemic regions where both genera co-exist and are associated with diarrhoeal disease. Our study underscores Aeromonas as an important environmental AMR reservoir and emerging multi-species pathogen capable of spilling over into human populations.

59 BASIC BIOLOGICAL SCIENCES↗

Repeated gain and loss of a single gene modulates the evolution of vascular plant pathogen lifestyles

Vascular plant pathogens travel long distances through host veins, leading to life-threatening, systemic infections. In contrast, nonvascular pathogens remain restricted to infection sites, triggering localized symptom development. The contrasting features of vascular and nonvascular diseases suggest distinct etiologies, but the basis for each remains unclear. Here, we show that the hydrolase CbsA acts as a phenotypic switch between vascular and nonvascular plant pathogenesis. cbsA was enriched in genomes of vascular phytopathogenic bacteria in the family Xanthomonadaceae and absent in most nonvascular species. CbsA expression allowed nonvascular Xanthomonas to cause vascular blight, while cbsA mutagenesis resulted in reduction of vascular or enhanced nonvascular symptom development. Phylogenetic hypothesis testing further revealed that cbsA was lost in multiple nonvascular lineages and more recently gained by some vascular subgroups, suggesting that vascular pathogenesis is ancestral. Our results overall demonstrate how the gain and loss of single loci can facilitate the evolution of complex ecological traits.

59 BASIC BIOLOGICAL SCIENCES↗

Complete Inactivation of Blood Borne Pathogen Trypanosoma cruzi in Stored Human Platelet Concentrates and Plasma Treated With 405 nm Violet-Blue Light

The introduction of pathogen reduction technologies (PRTs) to inactivate bacteria, viruses and parasites in donated blood components stored for transfusion adds to the existing arsenal toward reducing the risk of transfusion-transmitted infectious diseases (TTIDs). We have previously demonstrated that 405 nm violet-blue light effectively reduces blood-borne bacteria in stored human plasma and platelet concentrates. In this report, we investigated the microbicidal effect of 405 nm light on one important bloodborne parasite Trypanosoma cruzi that causes Chagas disease in humans. Our results demonstrated that a light irradiance at 15 mWcm -2 for 5 h, equivalent to 270 Jcm -2 , effectively inactivated T. cruzi by over 9.0 Log 10 , in plasma and platelets that were evaluated by a MK2 cell infectivity assay. Giemsa stained T. cruzi infected MK2 cells showed that the light-treated parasites in plasma and platelets were deficient in infecting MK2 cells and did not differentiate further into intracellular amastigotes unlike the untreated parasites. The light-treated and untreated parasite samples were then evaluated for any residual infectivity by injecting the treated parasites into Swiss Webster mice, which did not develop infection even after the animals were immunosuppressed, further demonstrating that the light treatment was completely effective for inactivation of the parasite; the light-treated platelets had similar in vitro metabolic and biochemical indices to that of untreated platelets. Overall, these results provide a proof of concept toward developing 405 nm light treatment as a pathogen reduction technology (PRT) to enhance the safety of stored human plasma and platelet concentrates from bloodborne T. cruzi, which causes Chagas disease.

405 nm light↗

Assessing residential activity in a home plumbing system simulator: monitoring the occurrence and relationship of major opportunistic pathogens and phagocytic amoebas

Opportunistic premise plumbing pathogens (OPPPs) have been detected in buildings’ plumbing systems causing waterborne disease outbreaks in the United States. In this study, we monitored the occurrence of OPPPs along with free-living amoeba (FLA) and investigated the effects of residential activities in a simulated home plumbing system (HPS). Water samples were collected from various locations in the HPS and analyzed for three major OPPPs: Legionella pneumophila, nontuberculous mycobacterial species (e.g., Mycobacterium avium, M. intracellulare, and M. abscessus), and Pseudomonas aeruginosa along with two groups of amoebas (Acanthamoeba and Vermamoeba vermiformis). A metagenomic approach was also used to further characterize the microbial communities. Results show that the microbial community is highly diverse with evidence of spatial and temporal structuring influenced by environmental conditions. L. pneumophila was the most prevalent pathogen (86% of samples), followed by M. intracellulare (66%) and P. aeruginosa (21%). Interestingly, M. avium and M. abscessus were not detected in any samples. The data revealed a relatively low prevalence of Acanthamoeba spp. (4%), while V. vermiformis was widely detected (81%) across all the sampling locations within the HPS. Locations with a high concentration of L. pneumophila and M. intracellulare coincided with the highest detection of V. vermiformis, suggesting the potential growth of both populations within FLA and additional protection in drinking water. After a period of stagnation lasting at least 2-weeks, the concentrations of OPPPs and amoeba immediately increased and then decreased gradually back to the baseline. Furthermore, monitoring the microbial population after drainage of the hot water tank and partial drainage of the entire HPS demonstrated no significant mitigation of the selected OPPPs. This study demonstrates that these organisms can adjust to their environment during such events and may survive in biofilms and/or grow within FLA, protecting them from stressors in the supplied water.

59 BASIC BIOLOGICAL SCIENCES↗

Comparative Genomics Applied to Systematically Assess Pathogenicity Potential in Shiga Toxin-Producing Escherichia coli O145:H28

Shiga toxin-producing Escherichia coli (STEC) O145:H28 can cause severe disease in humans and is a predominant serotype in STEC O145 environmental isolates. Here, comparative genomics was applied to a set of clinical and environmental strains to systematically evaluate the pathogenicity potential in environmental strains. While the core genes-based tree separated all O145:H28 strains from the non O145:H28 reference strains, it failed to segregate environmental strains from the clinical. In contrast, the accessory genes-based tree placed all clinical strains in the same clade regardless of their genotypes or serotypes, apart from the environmental strains. Loss-of-function mutations were common in the virulence genes examined, with a high frequency in genes related to adherence, autotransporters, and the type three secretion system. Distinct differences in pathogenicity islands LEE, OI-122, and OI-57, the acid fitness island, and the tellurite resistance island were detected between the O145:H28 and reference strains. A great amount of genetic variation was detected in O145:H28, which was mainly attributed to deletions, insertions, and gene acquisition at several chromosomal “hot spots”. Finally, our study demonstrated a distinct virulence gene repertoire among the STEC O145:H28 strains originating from the same geographical region and revealed unforeseen contributions of loss-of-function mutations to virulence evolution and genetic diversification in STEC.

59 BASIC BIOLOGICAL SCIENCES↗

BioNutrients-3: Precision Fermentation, Pasteurization, and Pathogen Detection - Towards Safe Fermentation and Production of Nutrients in Space

The BioNutrients (BN) project is developing a microbial manufacturing approach to supplement the NASA food system to address known nutrient degradation associated with long-term storage. BN uses synthetic biology to deliver high-value nutrients and therapeutics through genetic engineering of microbes and production of fermented food products like yogurt and kefir, in a fully dehydrated system. On-demand production of nutrients for human consumption requires rigorous safety protocols to ensure contaminants are not introduced during the fermentation process. The third iteration of the BN flight project, BN-3, further develops the BN project by investigating strategies for pathogen detection and pasteurization in microgravity. BN-3 will test the limits of pathogen detection using whole genome sequencing, standard microbial assays and the NASA Ames E-Nose, a volatile carbon nano tube-based sensor array, to detect unwanted microbes. BN-3 also expands on the number of nutrients produced in a single bioreactor to enhance efficiency of the system by combining production of B vitamins in conjunction with the carotenoids, beta-carotene and zeaxanthin. Serial production of food products through yogurt passaging, new updates to the fluorinated ethylene propylene bags to allow crew access via a straw, as well as use of a food safe pH indicator dye to indicate readiness of the food product, will further enhance the useability of this system. This presentation will provide status of the BN-3 flight project with the aim of advancing in-space biomanufacturing for on-demand microbially based food production for future space exploration.

Biomanufacturing↗

Assessing the Application of a Genomic Network Analysis in Population Ecology: Inferring Patterns of Dispersal and Geographic Structure in the Emerging Pathogen, Coccidioides

A challenge in population ecology studies is identifying how to best group individuals into populations, especially when individual origin is unknown. Machine learning has improved upon traditional methods of identifying population structure and is more efficient at handling large, complex datasets. We demonstrate the applicability of a machine learning method to identify hierarchical population structure in an emerging pathogen, Coccidioides spp., the causative agent of Valley fever. We compared the network clusters to structure identified by traditional tools as a validation of the network performance. We used publicly available whole-genome data for 48 C. immitis and 102 C. posadasii, resulting in 168,211 genome-wide SNPs among the two species. The network analysis grouped samples into populations comparable to the literature for these species but also identified fine-scale geographic structure and travel-associated cases not reported thus far. Exploring different resolutions in the network made it easy to identify unique genotypes specific to California and possibly Nevada, as well as Phoenix- and Tucson-acquired infections in non-endemic areas, regardless of reported travel history. The present study provides a promising example of how a ML-based network analysis can improve our ability to understand pathogen ecology, group cases into populations and infer travel-associated infections.

59 BASIC BIOLOGICAL SCIENCES↗

Modeling airborne pathogen transport and transmission risks of SARS-CoV-2

An integrated modeling approach has been developed to better understand the relative impacts of different expiratory and environmental factors on airborne pathogen transport and transmission, motivated by the recent COVID-19 pandemic. Computational fluid dynamics (CFD) modeling was used to simulate spatial-temporal aerosol concentrations and quantified risks of exposure as a function of separation distance, exposure duration, environmental conditions (e.g., airflow/ventilation), and face coverings. The CFD results were combined with infectivity models to determine probability of infection, which is a function of the spatial-temporal aerosol concentrations, viral load, infectivity rate, viral viability, lung-deposition probability, and inhalation rate. Uncertainty distributions were determined for these parameters from the literature. Probabilistic analyses were performed to determine cumulative distributions of infection probabilities and to determine the most important parameters impacting transmission. This modeling approach has relevance to both pathogen and pollutant dispersion from expelled aerosol plumes.

60 APPLIED LIFE SCIENCES↗

Xyloglucan processing machinery in Xanthomonas pathogens and its role in the transcriptional activation of virulence factors

Xyloglucans are highly substituted and recalcitrant polysaccharides found in the primary cell walls of vascular plants, acting as a barrier against pathogens. Here, we reveal that the diverse and economically relevant Xanthomonas bacteria are endowed with a xyloglucan depolymerization machinery that is linked to pathogenesis. Using the citrus canker pathogen as a model organism, we show that this system encompasses distinctive glycoside hydrolases, a modular xyloglucan acetylesterase and specific membrane transporters, demonstrating that plant-associated bacteria employ distinct molecular strategies from commensal gut bacteria to cope with xyloglucans. Notably, the sugars released by this system elicit the expression of several key virulence factors, including the type III secretion system, a membrane-embedded apparatus to deliver effector proteins into the host cells. Together, these findings shed light on the molecular mechanisms underpinning the intricate enzymatic machinery of Xanthomonas to depolymerize xyloglucans and uncover a role for this system in signaling pathways driving pathogenesis.

59 BASIC BIOLOGICAL SCIENCES↗