Pathogens最新文献

Gastrointestinal nematode (GIN) infections are the most prevalent parasitic diseases in grazing sheep worldwide, causing significant productivity losses, high mortality and, as a result, economic losses and emerging animal welfare concerns. Conventional control strategies, primarily relying on anthelmintic treatments, face limitations due to rising drug resistance and environmental concerns, underscoring the need for sustainable alternatives. Selective breeding for host genetic resistance has emerged as a promising strategy, while recent advances in transcriptomics and integrative omics research are providing deeper insights into the immune pathways and molecular and genetic mechanisms that underpin host-parasite interactions. This review summarizes current evidence on transcriptomic signatures associated with resistance and susceptibility to H. contortus and T. circumcincta GIN infections, highlighting candidate genes, functional genetic markers, key immune pathways, and regulatory networks. Furthermore, we discuss how other omics approaches, including genomics, proteomics, metabolomics, microbiome, and multi-omics integrations, provide perspectives that enhance the understanding of the complexity of the GIN resistance trait. Transcriptomic studies, particularly using RNA-Sequencing technology, have revealed differential gene expression, functional genetic variants, such as SNPs and INDELs, in expressed regions and splice junctions, and regulatory long non-coding RNAs that distinguish resistance from susceptible sheep, highlighting pathways related to Th2 immunity, antigen presentation, tissue repair, and stress signaling. Genomic analyses have identified SNPs, QTL, and candidate genes linked to immune regulation and parasite resistance. Proteomic and metabolomic profiling further elucidates breed- and tissue-specific alterations in protein abundance and metabolic pathways, while microbiome studies demonstrate distinct microbial signatures in resistant sheep, suggesting a role in modulating host immunity. In conclusion, emerging multi-omics approaches and their integration strategies provide a comprehensive framework for understanding the complex host-parasite interactions that govern GIN resistance, offering potential candidate biomarkers for genomic selection and breeding programs aimed at developing sustainable, parasite-resistant sheep populations.

Torque Teno Virus (TTV), a common and genetically diverse component of the human virome, is not linked to any known disease but reflects immune status. Its plasma viral load has shown clinical relevance in solid organ transplant recipients, correlating it with immunosuppression when present at high levels. However, the clinical significance of TTV viral load in hematopoietic stem cell transplantation (HSCT) recipients is less understood. This systematic review aims to evaluate whether plasma TTV DNA load directly correlates with the degree of T-cell immune reconstitution after HSCT, supporting its potential role as a biomarker for immune competence. The study protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD420251116208) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-one studies were included. The results showed concordant data about TTV kinetics with peak levels reaching approximately between +90 to +120 days after transplantation. Contradictory results have instead been found for the association of TTV load with immune parameters (lymphocyte counts, viral opportunistic infection, and development of acute graft versus host diseases). Even if a low-risk bias assessment was classified in most studies (67%), it was possible to identify important clinical and methodological differences between them, which might account for the different findings observed. Therefore, future larger studies with standardized protocols are needed to assess whether TTV viral load can serve as a reliable tool for guiding clinical decisions in the context of HSCT.

Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical illness affecting 6-8 million people in Latin America. Reaching scholarly consensus on the host response to T. cruzi infection remains a significant challenge, primarily due to substantial heterogeneity in outcomes driven by both the choice of animal model and the infecting parasite's discrete typing unit (DTU). This variability complicates the evaluation and comparison of new therapeutic compounds against existing drugs, namely benznidazole and nifurtimox. This study provides a comprehensive, kinetic, multifaceted characterization of the acute infection using the highly virulent T. cruzi Y strain (TcII) in outbred Swiss mice. Here, crucial infection parameters are presented, including the optimal infective dose, the parasitemia dynamics, tissue damage markers, hematological profiles, cytokine production (Th1/Th2/Th17/Th22), and molecular parasite identification in target organs (heart, colon, esophagus, spleen, and liver) across the span of the infection. The novelty of this study lies in the kinetic integration of these parameters within a defined model; rather than presenting isolated data points, we demonstrate how the biochemical, physiological, and clinical signs and immunological responses, with the resulting organ involvement, evolve and interact over time. To complete the report, a necropsy evaluation was performed at the end of the acute, fatal infection, and it is presented here. This study fulfills a long-standing recommendation from diverse drug discovery groups for the creation of a definitive reference model to standardize preclinical testing for anti-Chagasic agents.

American tegumentary leishmaniasis (ATL) and other infectious granulomatous diseases (IGDs) may present with oral/oropharyngeal mucosal lesions (OOPML). IGD-OOPML can result from fungal, parasitic, or bacterial infections, and squamous cell carcinoma (SCC) represents the main differential diagnosis. ATL, other IGD, and SCC share overlapping clinical and epidemiological features, making diagnostic suspicion challenging. This study compared sociodemographic and clinical characteristics among ATL, other IGD, and SCC. Descriptive, comparative, and multivariable logistic regression analyses were performed. Among 7551 patients, 213 met inclusion criteria (83-SCC and 130-IGD). Except for smoking, which differed only between ATL and SCC, most IGD parameters were similar. Male patients predominated in all groups. SCC patients were significantly older (p < 0.001) and had a shorter median disease duration (p = 0.007). The presence of pain increased the odds of SCC-OOPML by 3.96 times (95% CI 1.97-12.51). SCC patients were more likely to present lesions in a single subsite, either the oral cavity or oropharynx. Painful, ulcerated, or exophytic lesions favored SCC diagnosis, whereas infiltrative, granular, or mulberry-like lesions, involvement of multiple subsites, or associated nasal and laryngeal lesions suggested IGDs. Although clinical differentiation remains difficult, these findings may support early diagnostic suspicion, prompt treatment, and reduced sequelae.

Background: Pseudomonas aeruginosa is one of the leading agents causing healthcare-associated infections (HAIs) due to its intrinsic resistance, its capacity to acquire resistance mechanisms, and its persistence in hospital environments. In Mexico, it ranks among the most frequently reported pathogens in national surveillance systems. The aim of this study was to characterize antimicrobial resistance profiles and the genetic determinants associated with MDR/XDR phenotypes in P. aeruginosa strains from HAIs at Hospital Juárez de México (HJM).

Methods: Sixty-three strains from patients with HAIs were analyzed. Identification was confirmed by 16S rRNA gene sequencing. Antimicrobial susceptibility testing followed CLSI guidelines. MDR/XDR phenotypes were classified according to the Latin American consensus for categorizing MDR, XDR, and PDR pathogens. Screening for resistance mechanisms was carried out by PCR for the main β-lactamases circulating at HJM. Finally, mutations in the oprD gene were detected in imipenem-resistant isolates through amino acid sequence alignment.

Results: Resistant phenotypes allowed the identification of MDR and XDR profiles. Only the metallo-β-lactamase bla_VIM was detected. Analysis of oprD porin sequences revealed recurrent mutations (S103T, T115K, L170F, G186P, and T189V) associated with imipenem resistance.

Conclusions: In P. aeruginosa, the presence of bla_VIM and structural alterations in OprD confirms the multifactorial nature of carbapenem resistance. These findings underscore the need to strengthen microbiological surveillance programs and antimicrobial stewardship strategies to mitigate the impact and spread of MDR/XDR isolates.

Antimicrobial resistance (AMR) is a global threat to human, animal and environmental health, underscoring the need for integrated surveillance to understand its dynamics and ecosystem interactions. This study investigated the potential of swifts (Apus spp.), long-distance migratory birds, as valuable bioindicators of environmental AMR dissemination. Four sampling sessions were conducted over two years (2023-2024) at a wildlife rehabilitation center in Trieste, Italy. Buccal and cloacal swabs were collected from 47 swifts: 10 sampled at arrival and 37 before autumn migration. Swabs were streaked on selective media for targeted isolation of Enterobacterales, Bacillales and Lactobacillales, yielding 168 bacterial isolates. Bacteria were identified using MALDI-TOF and antimicrobial susceptibility was assessed through disk diffusion method, using ECOFFs values or "no inhibition zone" criterion. Of the 168 bacterial isolates, 51 (30.36%) were non-wild type (NWT), with highest percentages of NWT isolates for clarithromycin (33.33%), erythromycin (31.50%), clindamycin (21.88%) and tetracycline (14.29%). Methicillin-resistant staphylococci (45.83%) and carbapenem NWT isolates (9.38%) were also detected. Bacillales isolates showed significantly higher NWT proportion (58.33%; p < 0.0001) compared to Enterobacterales and Lactobacillales. These findings, in clinically healthy non-antimicrobial treated swifts, suggest environmental exposure to resistant bacteria, and support a possible role of swifts as bioindicators of environmental AMR contamination, highlighting the need to strengthen environmental AMR surveillance within a One Health perspective.

Urinary tract infections (UTIs) and urolithiasis exhibit a complex bidirectional relationship in which microbial colonization and urinary obstruction may mutually reinforce each other. This retrospective observational study evaluated clinical and microbiological factors associated with UTI in patients with urolithiasis using a large institutional dataset. A total of 23,241 urine cultures obtained from 12,708 unique patients were analyzed, comparing individuals with and without urolithiasis. In stone-forming patients, demographic variables, urine pH, hydronephrosis, ureteral double J stent presence and indwelling duration, urinary anomalies, and stone characteristics were assessed. Logistic regression identified independent associations, and ROC analysis defined optimal risk thresholds. UTI were more frequent in the stone group (34.5%) compared with non-stone forming patients (28.9%, p < 0.001). Escherichia coli was the most common uropathogen overall, whereas Klebsiella pneumoniae, Enterococcus faecalis, and Pseudomonas aeruginosa were significantly enriched in patients with stones. Elevated urine pH (OR: 6.37; CI: 2.67-15.19; p = 0.001) and hydronephrosis (OR: 9.14; CI: 3.74-22.35; p = 0.001) were independently associated with UTI. A stent dwell time above 29.5 days was associated with infection with 85% sensitivity and 54% specificity (AUC: 0.70; CI: 0.68-0.73), and urine pH 6.2 or higher was associated with infection with 86% sensitivity and 67% specificity (AUC: 0.77; CI: 0.75-0.80). These findings underscore that urine alkalinity, obstruction, and prolonged stenting are key factors associated with infection risk, supporting the need for careful stent management and timely microbiological evaluation in patients with urolithiasis.

Bacteriophages, traditionally viewed solely as antibacterial agents, are increasingly being studied for their immunomodulatory properties. In this study, we demonstrate that PM16 phage therapy not only effectively controls subcutaneous Proteus mirabilis infection in mice but also induces long-term specific humoral immunity against subsequent reinfection. This immunomodulatory effect was dose-dependent. In vitro, PM16 directly activates macrophages, leading to increased production of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and inducible nitric oxide synthase, and enhances macrophage bactericidal activity against P. mirabilis. We assume that the enhancement of the adaptive immune response is mediated not by the phage acting as a classical antigenic adjuvant but by its ability to prime innate immune cells, specifically macrophages. This priming leads to more efficient bacterial clearance, antigen presentation, and the formation of protective immunological memory.

Evidence on the contribution of human papillomaviruses (HPVs) to the development of esophageal papillomas is still controversial. Esophageal papillomatosis (EP) is considered an exceedingly rare, but distinct entity within esophageal proliferations, with about 57 cases published so far. Tissues derived from an EP case and from non-EP esophageal papillomas were investigated for the presence of HPVs and virus-positive specimens were subsequently analyzed for transcriptional activity and surrogate markers of infection. Low-risk type HPV6 DNA was detected in a subset of the esophageal papillomatous tissues, including EP, and a variant isolate belonging to lineage A. In the EP tissue, the abundant expression of the viral E6/E7 mRNA and the presence of HPV6-specific E1^E4 transcripts, the latter indicative of productive viral infection, were detected. An analysis of HPV-specific neutralizing antibodies in sera obtained from the EP case during natural infection as well as after HPV vaccination revealed that, despite extensive manifestation, HPV6-specific antibodies were absent during natural infection and only elicited after repeated HPV immunizations. Although limited by a small sample size, this exploratory study suggests a possible involvement of HPV6 in the development of EP. Furthermore, this study may contribute to the evidence distinguishing EP from less extensive forms of non-EP esophageal squamous papillomas.

Ascaris lumbricoides is one of the most epidemiologically significant soil-transmitted helminths, and the environmental persistence of its eggs is largely attributed to their robust structural architecture. The search for ovicidal alternatives capable of overcoming this barrier has increasingly focused on metallic nanoparticles obtained through biological synthesis. Scanning electron microscopy (SEM) was employed to evaluate the ultrastructural effects of silver nanoparticles (AgNPs) biosynthesised by the nematophagous fungus Duddingtonia flagrans on A. lumbricoides eggs. Ultraviolet-visible spectroscopy and transmission electron microscopy confirmed the synthesis of AgNPs, revealing predominantly spherical, well-dispersed particles with an average diameter of 9.22 ± 4.9 nm. Cytotoxicity assays indicated an IC₅₀ of 7.7 µg/mL. SEM analyses showed that eggs in the control group maintained intact morphology, with no apparent deformities. In contrast, exposure to AgNPs induced pronounced structural alterations, including marked wrinkling, surface erosion and shell collapse, suggesting disruption of multiple layers. Albendazole alone produced deep linear fissures consistent with internal metabolic failure, though with minimal external erosion. The combined treatment with AgNPs and albendazole resulted in severe degradation. These findings demonstrate that AgNPs exhibit significant ovicidal activity and may serve as effective adjuvants to enhance the action of conventional anthelmintics against highly resistant helminth eggs.