Pathogens最新文献

Sepsis remains a leading cause of global mortality and is characterized by a dysregulated host immune response to infection. Early deaths often result from hyperinflammation and organ dysfunction, whereas late-stage mortality is increasingly attributed to sepsis-induced immunosuppression, leading to secondary infections and viral reactivation. Challenges persist in the identification and management of sepsis-induced immunosuppression, including the lack of standardized immune monitoring methods, the absence of reliable immune biomarkers to guide therapy, and the limited success of immunomodulatory therapies in clinical trials. This review comprehensively summarizes the pathophysiology of sepsis-induced immunosuppression, encompassing immune cell apoptosis and exhaustion, the expansion and activation of immunomodulatory cells, metabolic reprogramming, epigenetic alterations, and iatrogenic factors. We also discuss current diagnostic challenges and explore emerging immunomodulatory strategies, such as cytokine therapies, immune checkpoint inhibitors, and metabolic modulators, as potential approaches to restore immune function. Finally, we highlight the importance of immune phenotyping and individualized precision medicine in the future management of sepsis, and integrating multidisciplinary approaches from mechanistic research to targeted therapies holds promise for improving patient outcomes.

The family Flaviviridae has been expanded to include the highly divergent flavi-like viruses into three new families, Flaviviridae, Pestiviridae, and Hepaciviridae, in the order Amarillovirales. Classical flavivirids are small, enveloped viruses with positive-sense ssRNA genomes lacking a 3' poly(A) tail and ~9.0-13.0 kb in length, with a single open reading frame (ORF) encoding structural proteins at the N-terminus and nonstructural proteins at the C-terminus. Members infect a wide range of mammals, birds, and insects, and many are host-specific and pathogenic. Although the RNA-directed RNA polymerase (RdRP) gene sequences of the flavi-like viruses group phylogenetically with those of classical flavivirids, flavi-like viruses often encode larger polyproteins and possess substantially longer genomes of up to ~40 kb, and some have a 3' poly(A) tail. Their host range extends across the whole animal kingdom and angiosperm plants. This review describes the reported flavi-like viruses of aquatic animals, providing a meaningful update on all three new families in Amarillovirales that have been discovered using metagenomics in fish, crustaceans, mollusks, and echinoderms. These amarilloviruses include pathogenic viruses of aquatic animals, such as Cyclopterus lumpus virus (CLuV) detected in moribund lumpfish, and infectious precocity virus (IPV) found in iron prawn syndrome (IPS)-affected farmed giant freshwater prawns.

Faecal egg counts (FECs) are used to assess the intensity of gastrointestinal nematode (GIN) infections in herbivores. FEC distribution is aggregated, meaning that approximately 20% of animals harbour 80% of infections. In times of escalating anthelmintic resistance, it may be necessary to restrict treatment to the animals with the heaviest infections. This strategy is called targeted selective treatment (TST) and is relevant to GIN, for example. The difficulty lies in identifying which animals to treat. One solution is to select potentially at-risk animals based on age (for example, treating the young) or to perform individual faecal egg counts (though this is costly). We propose a solution for determining the suitability of selective treatment based on the level of FEC (200 or 500 eggs per gram of faeces). First, we demonstrated that the mean FEC in a group is strictly related to its variance (Taylor's power law) using published data and our own unpublished data on horses from France, Poland, and Mexico. The study focused on small and large strongyles in horses. Taylor's power law states that sample variance (Var) and the population mean are related by a simple equation: Var = a Mean^b or log(Var) = log(a) + b log(Mean). The influence of factors such as age, status (mare, stallion, yearling, etc.), day-to-day variability, and previous anthelmintic treatments did not alter this relationship. To reduce the number of FECs, we estimated the mean FEC on a composite faecal sample. We then calculated the variability and therefore the number of horses with an FEC above the chosen acceptable level. When the mean is high, the number of horses to be treated is also high and TST is not beneficial. When the FEC is average, TST may be worthwhile, either based on the FEC of individual horses or on the horse class at risk. Based on the percentage of horses with an FEC above the acceptable level, farmers can decide whether to treat all animals or establish a TST protocol. Caution should be exercised when using TST in the presence of large strongyles.

Enteroviruses (EVs) are major pathogens transmitted via direct and indirect contact, with children being particularly susceptible. As EVs persist on surfaces, environmental hygiene is critical in communal environments. We investigated EVs presence on environmental surfaces in daycare centers from April to July 2024. Environmental samples (300) were collected from floors, toys, and desks. Viral RNA was extracted and analyzed using real-time reverse transcription polymerase chain reaction (real-time RT-PCR) and ddPCR to detect pan-Enterovirus (pan-EVs) and Enterovirus D68 (EV-D68). EVs were detected in 45.3% of the samples. The detection rate refers to the combined results, including both ddPCR and real-time PCR. Specifically, pan-EVs were found in 88 samples (1.12-505 copies/20 μL) and EV-D68 in 104 samples (1.12-309 copies/20 μL). Floors (31%) were the most contaminated surfaces. Monthly analysis showed a gradual decrease in detection rates from 88.6% in April to 18.5% in July, appearing to align with the implementation of enhanced hygiene measures. However, this trend may also reflect multifaceted factors, including natural viral reduction, exclusion of symptomatic children, and increased hygiene awareness. Notably ddPCR (83.0%) exhibited nearly twice the detection rate of real-time RT-PCR (42.5%), identifying low-level viral persistence. These findings suggest that environmental surfaces serve as reservoirs for transmission, and integrating sensitive detection like ddPCR with proactive hygiene management may help mitigate EVs spread.

Hepatitis B virus (HBV) pregenomic RNA (pgRNA), transcribed directly from nuclear covalently closed circular DNA (cccDNA), is an essential component in viral replication. The synthesis and encapsidation of pgRNA depend significantly on the transcriptional activity of cccDNA, making serum pgRNA a recently recognized non-invasive biomarker for evaluating cccDNA activity. However, its clinical application is limited by factors including preanalytical variables, methodological inconsistencies in detection, and a lack of standardization in quantification. This review provides an overview of the biological origins of pgRNA and its critical role in the HBV replication cycle, highlighting the stability challenges encountered during the collection, processing, and storage of plasma/serum samples. Furthermore, it analyzes recent significant advancements in pgRNA detection technologies, encompassing modified reverse transcription quantitative polymerase chain reaction (RT-qPCR), nucleocapsid-captured methodologies, automated testing platforms, multiplex digital PCR, isothermal amplification, and clustered regularly interspaced short palindromic repeats-based assays. A comparison of these technologies revealed that discrepancies in pgRNA quantification arise primarily from variations in sample processing and measurement systems, rather than from inherent biological limitations. Therefore, establishing standardized sample handling procedures, harmonized detection methods, and unified measurement systems is imperative before pgRNA can be reliably applied to monitor treatment, guide cessation decisions, or evaluate cure in chronic hepatitis B.

Urban forests are highly valued for the multiple benefits they provide to city dwellers. The strategic provision of ecosystem services by these forests is threatened by climate change, warming conditions being responsible for heat waves and chronic droughts that inflict stress and mortality on trees. A three-year study (2011-2013) conducted at Parco Nord Milano (PNM) (Milano, Italy) assessed the impact of thinning interventions on the dynamics of fungal pathogens in declining forest plots. Symptomatic trees of the genera Alnus, Acer, Fraxinus, Platanus, Quercus and Ulmus, exhibited in thinned subplot pronounced decline/dieback, exhibiting symptoms like microphyllia, leaf yellowing, leaf shedding, sunken cankers, shoot wilting and branch dieback. Comparative analyses between the thinned and unthinned subplots revealed a significantly higher incidence of pathogens in the thinned one. Five species of Botryosphaeriaceae, namely Botryosphaeria dothidea, Diplodia corticola, Diplodia seriata, Dothiorella omnivora and Neofusicoccum parvum, were consistently isolated from tissues of declining hosts. There is evidence that thinning altered plot-level microclimate conditions and microbial equilibrium, favoring the proliferation of latent, pathogenic Botryosphaeriaceae. In fact, during the study period, the presence of N. parvum increased tenfold and that of B. dothidea fivefold in thinned subplot. Conversely, in unthinned subplot, the same pathogenic taxa maintained stable proportions. These results demonstrate that thinning altered ecological balances increasing tree susceptibility to harmful, cosmopolitan botryosphaeriaceous fungi. Our findings challenge assumptions about thinning as a universally beneficial practice, emphasizing the need for silvicultural strategies that take into account host and pathogen ecology and the microclimatic resilience of forest stands. This study emphasizes the importance of adaptive management in urban forestry to mitigate the unintended ecological consequences of climate change.

Background: Data on long-term sequelae after severe imported Plasmodium falciparum malaria in adults are scarce in non-endemic settings. We aimed to quantify early and medium term renal and neurological outcomes and identify prognostic factors. Therapeutic strategies have evolved with widespread intravenous artesunate, yet survivorship data remain limited.

Methods: We performed a retrospective study of cases of severe malaria at the University Hospital of Marseille (France) between January 2018 and December 2024. This study is a single-centre retrospective cohort with prospective follow-up using standardised questionnaires. Adults meeting the criteria for severe falciparum malaria were included. The primary endpoint was a composite of renal impairment and/or neurological sequelae assessed at day 28 (D28) and at remote post-discharge follow-up. Patient-reported outcomes were collected at one year. Associations with baseline features were tested using the Fisher's exact and Wilcoxon-Mann-Whitney tests.

Results: Among 474 malaria cases, 66 (13.9%) were severe; of these, 57 met inclusion criteria. Fifty-seven of them were included. All received intravenous artesunate with oral step-down; 35% required ICU care. At D28, 6/41 patients (14.6%) had sequelae (four renal, one neurological, one both). Sequelae at D28 were associated with neurological failure (66.7% vs. 14.3%; p = 0.015), severe metabolic acidosis (50.0% vs. 2.9%; p = 0.007) and renal impairment at admission (83.3% vs. 2.9%; p < 0.001). At remote follow-up, 6/33 patients (18.2%) had sequelae (two renal, three neurological, one both), associated with older age (61.0 ± 5.3 vs. 39.8 ± 15.8 years; p = 0.008), D3 blood smear positivity (66.7% vs. 11.5%; p = 0.012), neurological failure (66.7% vs. 18.5%; p = 0.034) and renal impairment (50.0% vs. 7.4%; p = 0.031). No deaths or relapses occurred. At one year, patient-reported outcomes (n = 14) showed persistent symptoms in 8/14, chiefly fatigue and cognitive complaints.

Conclusions: In a high-resource, non-endemic setting, renal and neurological sequelae after severe imported malaria are frequent at D28 and persist in nearly one-fifth of cases during post-discharge follow-up. Neurological failure, metabolic acidosis, renal impairment at presentation, older age and D3 blood smear positivity identify patients at risk and support risk-stratified post-discharge follow-up.

Hibernation profoundly alters host-pathogen dynamics by suppressing metabolism and immune function, posing unique challenges for infection control. In this study, we examined how genomic variation modulates infection and physiological traits in temperate bats during hibernation. We combined infection screening, haematology, blood biochemistry, and whole-genome sequencing across five vespertilionid species, identifying over 170,000 single nucleotide variants (SNVs) and assessing their associations with 23 health-related variables. Using the phylogenetically informed treeWAS framework, we detected 515 significant SNVs linked to traits including fungal, protozoan and bacterial infections, acid-base balance, and blood cell indices. These SNVs mapped to 137 unique genes, which were enriched for functional domains related to cytoskeletal dynamics, membrane trafficking, and intracellular signalling (e.g., SH3, C2, BAR, semaphorin). Notably, canonical immune effector genes were underrepresented, and several trait-associated SNVs appeared in blocks across multiple scaffolds, pointing to regulatory loci as key modulators of hibernator health. Our findings support the hypothesis that bats rely on infection tolerance rather than resistance during hibernation, with genomic variation in regulatory and signalling pathways shaping their physiological responses to infection under energy-limited conditions.

Oocysts of Toxoplasma gondii exhibit remarkable resistance to environmental stressors and most conventional disinfectants. Despite its ability to infect a wide variety of host species, sexual reproduction and oocyst formation occur exclusively within felid definitive hosts. Despite the epidemiological significance of oocyst-mediated transmission, the molecular mechanisms governing oocyst production and sporulation remain incompletely understood. Glutaredoxin, serving as a central regulator of cellular redox homeostasis and multiple vital cellular processes in cells, is a potential regulator for oocyst sporulation. Here, we investigated the role of TGME49_227100 (glutaredoxin 5, Grx5) in the T. gondii Pru strain-a type II strain capable of oocyst formation, with a particular focus on its functions during oocyst formation and sporulation. We found that Grx5-knockout tachyzoites exhibited no defects in growth or virulence. Neither in vitro nor in vivo tachyzoite-to-bradyzoite differentiation was affected compared to wild-type parasites. Notably, Grx5 deletion significantly reduced oocyst production in cats by approximately 70%. Additionally, the collected oocysts showed a 50% decrease in sporulation rate. These results indicate that Grx5 plays a predominant role within feline host and the external environmental stage of sporulation, which of these is likely to provide a crucial molecular target for developing a transmission-blocking vaccine.

Cyclic di-GMP (bis-(3'→5') cyclic dimeric guanosine monophosphate) is a ubiquitous bacterial second messenger that regulates a wide range of cellular processes, including biofilm formation, motility, virulence, and environmental adaptation. Its intracellular levels are dynamically controlled by diguanylate cyclases (DGCs), which synthesize c-di-GMP from GTP, and phosphodiesterases (PDEs), which degrade it into linear pGpG or GMP. The functional effects of cytoplasmic c-di-GMP are mediated through diverse effector proteins, including PilZ domain-containing receptors, transcription factors, and riboswitches. In Leptospira interrogans, a major pathogenic species responsible for leptospirosis, the regulatory roles of c-di-GMP remain poorly understood. Here, we performed a comprehensive bioinformatics and structural analysis of all predicted c-di-GMP related proteins in L. interrogans serovar Copenhageni strain Fiocruz L1-130, a serovar generally associated with severe manifestations of leptospirosis in humans. Our analysis identified seventeen proteins containing GGDEF domain, five proteins containing both GGDEF and EAL domains, four proteins containing EAL domain, five proteins containing HD-GYP domain, twelve proteins containing PilZ domain, and one protein containing an MshEN domain. Comparative analysis with well-characterized bacterial homologs suggests that L. interrogans possess a complex c-di-GMP signaling network, likely involved in modulating biofilm formation, host-pathogen interactions, and environmental survival. These findings provide new insights into the c-di-GMP regulatory network and on signal transduction in Leptospira and lay the foundation for future functional studies aimed at understanding its roles in physiology, virulence, and persistence.