Search Results (245)

Concurrent multiple myeloma (MM) and AL amyloidosis is associated with the poorest outcomes among plasma cell dyscrasias and has dramatically reduced median overall survival. Despite their clinical significance, comprehensive systematic histopathological studies, characterizing multiorgan involvement and lesion severity are remarkably scarce. This study includes 24 autopsies (of 18 women and six men; median age—68 years) with MM-AL. Immunohistochemical (IHC) typing was performed with an expanded antibody panel targeting the amyloid precursor protein; anti-human CD138 antibody was used to identify plasma cells in bone marrow sections. Clinical diagnosis of MM with monoclonal G-lambda secretion, Durie–Salmon Stages II–III, was established in 17 (71%) patients; MM with monoclonal G-kappa secretion, Stage III, in five (21%); and non-secreting MM in two (8%). Systemic amyloidosis was revealed during life in only 15 (62.5%) patients. In all cases, extensive amyloid deposits were observed in the myocardium, lungs and kidneys, establishing the morphological basis for multiorgan failure. IHC typing of amyloids confirmed 18 (75%) cases of AL-lambda amyloidosis and six (25%) of AL-kappa amyloidosis. Our results clarify MM-AL morphogenesis and underscore that AL is frequently underdiagnosed in MM patients. Comprehensive histopathological studies with IHC typing are necessary to confirm the diagnosis, refine the prognosis, and optimize the therapeutic strategies. Full article

Endometriosis is a chronic inflammatory disease in which transforming growth factor-beta (TGF-β) has been implicated in immune dysregulation, extracellular matrix remodeling, and fibrosis. Data on baseline secretion of TGF-β isoforms by systemic immune cells remain limited. This pilot study quantified unstimulated secretion of TGF-β1, TGF-β2, and TGF-β3 by peripheral blood mononuclear cell (PBMC) cultures from women with and without endometriosis and explored stage-related patterns. In this prospective case–control study, PBMCs from 50 women with surgically confirmed endometriosis and 30 controls were cultured for 24 h without exogenous stimulation. Supernatant concentrations were measured using a multiplex bead-based immunoassay (Bio-Plex, Bio-Rad) and expressed as pg/mL; between-group and stage-related differences were assessed using non-parametric tests. Median 24 h secretion was similar between groups (TGF-β1: 103,816 vs. 114,700 pg/mL, p = 0.25; TGF-β2: 3735 vs. 3732 pg/mL, p = 0.32; TGF-β3: 3280 vs. 3284 pg/mL, p = 0.70). Within the endometriosis cohort, TGF-β2 was significantly higher in moderate/advanced disease (rASRM stages III–IV) than in minimal/mild disease (stages I–II), whereas TGF-β1 and TGF-β3 did not reach statistical significance for a stage-dependent pattern in this pilot cohort (p = 0.42 and p = 0.41, respectively; Kruskal–Wallis), and a type II error cannot be excluded given the small sample size per rASRM (revised American Society of Reproductive Medicine)stage (n = 11–14). These findings suggest that TGF-β dysregulation is compartmentalized to the peritoneal environment rather than systemically imprinted in circulating immune cells. The stage-dependent elevation of TGF-β2 supports its role in progressive fibrogenesis and as a candidate severity biomarker, warranting confirmation in larger, stimulus-augmented studies. Full article

Lysobacter antibioticus Hz25 is a novel strain that was isolated from the rhizosphere of the relict endemic plant Hedysarum zundukii Peschkova (Fabaceae), which grows on carbonate soils in the Baikal region of Russia. This work presents the complete genome sequence of Hz25 (5.98 Mb, 66.94% GC), which was obtained using a hybrid assembly method combining Oxford Nanopore and Illumina sequencing. Phylogenetic analysis based on 47 Lysobacter genomes and an average nucleotide identity (ANI) value of 96% confirmed its affiliation with L. antibioticus. A comparative pan-genome analysis with three closely related strains (13-6, 76, and ATCC 29479) identified 554 strain-specific genes. This significant genomic plasticity likely reflects adaptation to the sharply continental climate, high insolation, and low free iron content of the native soil. The genome encodes a comprehensive micropredator arsenal, including: seven chitinase genes (GH18 and GH19 families); bacteriolytic enzymes (Blp, L1, L4, Ami); a complete type III secretion system (T3SS) with predicted effectors; type IV pili (including the PilZ-PilB regulatory complex); and siderophore biosynthesis genes (lysochelin). The genome contains genes ars of an arsenic resistance system, but lacks the ACR3 efflux pump, suggesting that these genes may have alternative functions. Genes involved in calcium homeostasis (Excalibur domain, Na⁺/Ca²⁺ antiporter) were also identified. These features make Hz25 a promising candidate for biocontrol applications in cold climates and metal-contaminated environments. Full article

Background/Objectives: Melioidosis, caused by Burkholderia pseudomallei, is a severe tropical infectious disease associated with high mortality in endemic regions. Early diagnosis remains challenging because conventional diagnostic methods, including culture, serological assays, and molecular techniques, have limitations in sensitivity, specificity, processing time, and accessibility in resource-limited settings. This review evaluates current diagnostic approaches and highlights the potential of short peptide biomarkers for improving melioidosis detection. Methods: A narrative literature review was conducted using four electronic databases (PubMed, Scopus, Web of Science, and Google Scholar) covering publications from 2000 to 2024. Relevant studies were identified using predefined keywords related to melioidosis diagnostics, biomarkers, and peptide-based approaches, and were screened based on relevance to diagnostic methods and peptide biomarker development in Burkholderia pseudomallei. Results: Several biomarkers have been investigated for melioidosis diagnostics, including capsular polysaccharide (CPS), type III secretion system 1 (TTS1), and other virulence-associated proteins such as Hcp1 and BPSS1187. Among these, CPS and TTS1 are highly conserved and specific targets widely used in molecular and antigen-based detection methods. Short peptide epitopes derived from these antigens demonstrate promising advantages over whole proteins, including improved stability, high specificity, easier synthesis, and reduced production costs. Advances in epitope prediction technologies and peptide-based biosensors have further expanded the potential applications of short peptides in rapid diagnostic platforms, including ELISA, lateral flow immunoassays, and biosensor-based detection systems. Conclusions: Short peptide–based biomarkers represent a promising strategy for developing rapid, sensitive, and cost-effective diagnostic tools for melioidosis, particularly in endemic and resource-limited settings. Full article

Salmonella enterica infection remains a major threat to poultry health and food safety, largely due to its ability to invade the intestinal epithelium, modulate host immunity, and persist intracellularly. Curcumin, a bioactive phytochemical, has shown promising antimicrobial and immunomodulatory potential; however, its precise molecular interplay with host and pathogen systems remains unclear. An integrated computational pipeline was applied, combining target prediction, host immune network construction, Salmonella virulence interaction analysis, STRING-based PPI mapping, KEGG/GO enrichment, and molecular docking validation. Host immune hub genes and Salmonella virulence regulators were identified, followed by docking of curcumin to key host (AKT1, STAT3, TNF) and pathogen proteins (invA, phoP, ssrB). Host network analysis revealed enrichment in the PI3K–AKT, NF-κB, FoxO, and IL-10 signaling pathways, indicating roles in epithelial protection, immune regulation, inflammation suppression, and antioxidant defense. Salmonella virulence hubs were primarily associated with epithelial invasion, Type III secretion, intracellular survival, and global virulence reg-ulation. Docking analysis demonstrated a strong binding affinity of curcumin toward AKT1 (−7.4 kcal/mol), STAT3 (−6.5 kcal/mol) and TNF (−5.8 kcal/mol), supporting host immunomodulation and epithelial protection. Simultaneously, curcumin showed notable affinity for phoP (−6.8 kcal/mol), invA (−6.3 kcal/mol), and ssrB (−5.8 kcal/mol), suggesting the potential suppression of virulence signaling, invasion machinery, and intracellular persistence. This integrated host–pathogen systems analysis demonstrates that curcumin exerts a dual regulatory effect by enhancing host immune protection while concurrently disrupting Salmonella virulence mechanisms. These findings provide mechanistic insight supporting curcumin as a promising natural therapeutic candidate for controlling Salmonella infection in broilers. Full article

Cross-kingdom pathogenesis—human and animal pathogens colonizing and persisting in plants—is transforming our understanding of microbial ecology, food safety, and public health. This review translates incoming research that demonstrates plants as more than mute carriers to dynamic ecological interfaces where human and zoonotic pathogens, such as Salmonella enterica, Escherichia coli O157:H7, and Listeria monocytogenes, will adhere, internalize, and, in some cases, potentially evade host defenses. Such pathogens exploit evolutionarily conserved molecular processes like Type III secretion system 1 (TTSS), biofilm formation, quorum sensing, and small RNA-mediated immune sabotage that have allowed them to cross biological kingdom boundaries. To provide an entry point for pathogens, environmental conditions (e.g., contaminated irrigation water, manure application, wildlife access, and mechanical wounding) promote pathogen transfer to and penetration into plant tissues through stomata hydathodes above ground or roots below ground. Once inside, pathogens confront a range of plant immune responses, indigenous microbiota, and abiotic stresses such as UV radiation exposure, nutrient starvation, and osmotic fluctuations. Nonetheless, biofilm production, metabolic versatility, and virulence gene expression contribute to their persistence. Interactions with plant pathogens and microbiomes additionally shape colonization dynamics, for example, through co-survival and niche manipulation. With the acceleration of these processes due to climate change, urbanization, and intensified agriculture, cross-kingdom pathogenesis becomes a rising concern for One Health. Critical knowledge gaps, including seedborne transmission, microbiome engineering, and predictive modeling, are pointed out in the review along with emerging mitigation strategies, including point-of-care diagnostics and microbial biocontrol. In conclusion, this review advocates for interdisciplinary collaboration from microbiology, plant science, and One Health perspectives to predict and mitigate cross-kingdom threats to global food production. Full article

Salmonella remains a leading cause of foodborne illness worldwide, with non-typhoidal Salmonella (NTS) responsible for an estimated 93.8 million infections and substantial global morbidity and mortality. This review synthesizes current evidence on the epidemiology, molecular pathogenesis, and prevention of both typhoidal and nontyphoidal Salmonella, with emphasis on emerging challenges in disease control. We highlight key virulence mechanisms, including Salmonella pathogenicity islands and Type III secretion systems, that mediate host cell invasion, intracellular survival, and immune modulation, alongside differences in host adaptation, reservoirs, and clinical outcomes between major serotypes. Epidemiological synthesis demonstrates marked geographic variability in disease burden, driven by underreporting, limited diagnostic capacity, and social determinants of health, with particularly high mortality from invasive NTS (iNTS) disease in sub-Saharan Africa. This review further identifies major challenges, including the global rise of multidrug-resistant Salmonella lineages, the emergence of high-risk serotypes such as monophasic S. Typhimurium and S. Infantis, and the increasing complexity of transmission across the farm-to-fork continuum. While advances in whole genome sequencing and integrated surveillance platforms (e.g., PulseNet and GenomeTrakr) have improved outbreak detection and source attribution, gaps in cross-sector coordination persist. Collectively, the evidence underscores the need for integrated One Health approaches that link human, animal, and environmental systems, alongside strengthened surveillance, targeted prevention strategies, and antimicrobial stewardship. Advances in vaccination, including licensed typhoidal vaccines such as Ty21a and Vi polysaccharide, and conjugate vaccines, as well as emerging live attenuated and glycoconjugate candidates targeting NTS, represent promising strategies for reducing the global burden of Salmonella infections. Future efforts should focus on improving global surveillance harmonization, addressing environmental and climate-related drivers of transmission, and advancing vaccine development and implementation. Full article

The opportunistic pathogen Pseudomonas aeruginosa poses a serious threat to immunocompromised patients. Monosodium glutamate (MSG), a widely used flavor enhancer, has been reported to possess anti-inflammatory and antioxidant properties. However, its therapeutic potential and mechanism against Pseudomonas aeruginosa (P. aeruginosa) infection have remained unexplored. This study systematically elucidated the protective effects and molecular mechanisms of MSG against P. aeruginosa-induced acute lung injury (ALI). In a murine pneumonia model, MSG administration effectively alleviated lung pathological damage, edema, and inflammatory responses. Mechanistically, MSG exerted protection through a multifaceted strategy, including direct suppression of bacterial virulence via binding to PopB of T3SS inhibition of the TLR4/MyD88/MAPK-driven inflammatory cascade and pro-inflammatory cytokine production, enhancement of endogenous antioxidant defense (SOD, CAT), and reshaping of pulmonary macrophages from the M1 to M2 phenotype. Notably, the anti-virulence effect of MSG, achieved by binding to PopB (K_D = 3.52 × 10⁻⁶ M), presented a distinct advantage over traditional antimicrobials by potentially mitigating resistance development. Collectively, these findings indicated that MSG can alleviate ALI caused by P. aeruginosa infection. Full article

Siderophores are classically understood as microbial iron-acquisition metabolites: low-molecular-weight ligands secreted by bacteria to solubilize and transport Fe(III) under iron-limited conditions. In this review, we expand that paradigm by highlighting an emerging and underappreciated chemical axis—boron coordination by siderophores—that links terrestrial (soil/rhizosphere) and marine microbiomes. Across diverse bacterial taxa, siderophore production is widespread and central to competitive fitness because Fe(III) is poorly soluble and frequently sequestered in environmental or host matrices. Yet in boron-rich settings (seawater and borate-enriched soils), the same oxygen-donor architectures that support Fe(III) chelation can also engage boron chemistry. We synthesize evidence that carboxylate/α-hydroxyacid (dicitrate-type) and catecholate siderophores can form tetrahedral borate/boronate complexes, whereas hydroxamate siderophores generally lack the vicinal dianionic O,O motif required for stable boron binding. Structurally characterized examples—including vibrioferrin, rhizoferrin, and petrobactin—demonstrate that boron complexation is experimentally observable by ESI-MS and multinuclear NMR and can be modulated by pH and microenvironment. Integrating these findings with datasets on boron-tolerant bacteria, we propose that when iron is scarce and boron is available, boron–siderophore complexation becomes chemically feasible and may influence microbial physiology by altering ligand conformation, metal selectivity, and potentially extracellular signaling behavior—especially in marine systems where borate is abundant at oceanic pH. Overall, this review frames boron-binding siderophores as a cross-ecosystem phenomenon and a promising conceptual bridge between environmental boron geochemistry, microbial metal economy, and metalloid-mediated signaling. Full article

V. parahaemolyticus has several virulence factors, including thermostable direct hemolysin (TDH), TDH-related hemolysin (TRH), and two separate type III secretion systems (T3SSs), T3SS1 and T3SS2. T3SS1 is responsible for cytotoxicity, primarily through the activity of its effector VP1680. To gain a detailed understanding of the relationship between the amount of effector, its expression timing, and cytotoxicity, a system is required to regulate protein expression levels and timing. In the present study, we developed an effector protein expression system controlled by an arabinose-dependent transcription factor and found that cytotoxicity toward mammalian cells increased in a VP1680-dependent manner. To ensure specific protein degradation, we also established a targeted protein degradation system, including VP0917 (ClpP) and VP0918 (ClpX)-, or VP0917 and VP1014 (ClpA)-mediated degradation of ssrA-tagged proteins (proteins bearing the C-terminal degradation tag encoded by tmRNA). By combining these systems, more than 50% of the targeted protein could be degraded within 20 min. As a byproduct of creating the systems, we obtained an enhanced green fluorescent protein variant that emits strong fluorescence in V. parahaemolyticus. The protein degradation system developed in this study has demonstrated the potential to control intracellular protein levels to a certain extent. Moreover, experimentally controlling intracellular protein levels will allow for a more detailed examination of the relationship between protein quantity and cellular phenotype, potentially overcoming the limitations of the “all-or-nothing” model. Full article

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) has been added to the World Health Organization’s list as a high-priority pathogen for which new antibiotics are urgently needed. Herein, we investigated the association between resistance/virulence genes and high-risk CRPA clinical isolates by whole genome sequencing (WGS). Methods: Between 2019 and 2025, twenty-six CRPA strains from patients hospitalized in the “Renato Dulbecco” University Hospital were characterized. WGS analysis was performed using the next generation sequencing (NGS) technique. Multi-locus sequence typing (MLST) prediction was performed. Antibiotic resistance genes were detected using Antibiotic Resistance Gene-ANNOTation, Comprehensive Antibiotic Resistance Database, and ResFinder. Virulence genes were identified by the Virulence Factor Database. Results: The MLST analysis detected 14 different sequence types (ST). The 26 strains exhibited the same resistome profile: aac(3)-Ic, aphA15, catB7, catB10, cmlA, blaCARB, blaVIM-1, and tetG genes. The genes encoding enzymes involved in resistance to chloramphenicol and beta-lactams were found in all isolates using the three databases. Biofilm formation genes, metalloproteinase, chemotaxis, fimbriae, and pyoverdine were identified in all strains. Genes of the type III secretion system exoS, exoT, exoU, and exoY were found in 46.15%, 84.61%, 53.84%, and 84.61% of the strains, respectively. Conclusions: The analysis of the 26 clinical isolates showed high clonal heterogeneity, with a predominance of ST235, a high-risk clone associated with multiple resistances. Interestingly, cefiderocol resistance was carried by 4/8 isolates belonging to the ST235 strain. The surveillance based on resistome and virulome analysis could monitor the dynamic evolution of high priorityhigh-priority pathogens to guide clinical treatment and to adapt healthcare control measures, limiting their spread in the near future. Full article

Multidrug-resistant Pseudomonas aeruginosa is a major cause of healthcare-associated infections, particularly in high-burden clinical settings where rapid tools to capture clinically relevant resistance and virulence phenotypes are needed. In this study, we applied an integrated whole-genome sequencing (WGS) and Fourier-transform infrared (FTIR) spectroscopy approach to evaluate genotype–phenotype relationships in multidrug-resistant P. aeruginosa isolates collected during the COVID-19 pandemic. High-quality WGS data were used to characterize antimicrobial resistance determinants, mobile genetic elements, and virulence gene repertoires, while FTIR spectroscopy provided culture-based phenotypic fingerprints reflecting cell envelope composition. Genomic analyses revealed a conserved efflux-centered intrinsic resistance backbone, variably supplemented by acquired β-lactamases and aminoglycoside-modifying enzymes, alongside a largely conserved core virulome with heterogeneity driven primarily by type III secretion system effector profiles. Comparison of FTIR- and WGS-derived distance matrices revealed a weak but statistically significant global association, indicating a non-linear relationship between genomic relatedness and phenotypic similarity. Cluster-level concordance was strongly scale-dependent, with high agreement emerging only at finer clustering resolutions, consistent with FTIR capturing phenotypic variation linked to regulatory, metabolic, and cell envelope adaptations rather than deep phylogenetic structure. Together, these findings show that multidrug resistance and virulence in P. aeruginosa are shaped by a modular genomic architecture that manifests as distinct, measurable phenotypic states. The observed scale-dependent concordance supports FTIR spectroscopy as a rapid, cost-effective phenotypic screening tool for outbreak-oriented surveillance, complementing WGS in integrated antimicrobial resistance monitoring workflows. Full article

The genus Xanthomonas comprises devastating plant pathogens responsible for significant yield losses in globally critical crops such as rice (Oryza sativa L.), citrus (Citrus L. spp.), cassava (Manihot esculenta Crantz), and tomato (Solanum lycopersicum L.). This review synthesizes current knowledge on the molecular mechanisms driving Xanthomonas pathogenicity, including the type III secretion system (T3SS) that translocates effector proteins, transcription activator-like effectors (TALEs) that reprogram host transcription, and extracellular polysaccharides (EPS) that promote biofilm formation and immune evasion, which collectively enable host colonization, immune suppression, and disease progression. Rapid adaptation through genomic plasticity and horizontal gene transfer (HGT) exacerbates challenges in disease management by facilitating evasion of host defenses and environmental stressors. Economically, Xanthomonas spp. inflict billions in annual losses through crop damage, trade restrictions, and eradication efforts, disproportionately affecting resource-limited regions. Emerging antibiotic resistance and climate-driven shifts in pathogen distribution further threaten food security. Sustainable strategies, such as CRISPR-based genome editing to disrupt susceptibility genes, biocontrol agents (e.g., Bacillus and Pseudomonas spp.), and nanotechnology-driven antimicrobials offer promising alternatives to conventional copper-based and chemical controls. This review underscores the urgent need for integrated, climate-resilient management approaches to mitigate the ecological and socioeconomic impacts of Xanthomonas diseases, bridging genomic insights with innovative control measures, to address escalating threats posed by these pathogens in a changing global climate. Full article

Bacterial pathogens exploit host-derived nutrients to coordinate metabolism and virulence determinants to optimize fitness in vivo. In Pseudomonas aeruginosa, GlnK is a central regulator of nitrogen metabolism. It senses the intracellular nitrogen status by integrating 2-oxoglutarate (2-OG) and glutamine signals, which in turn triggers its uridylylation and conformational changes. This reversible post-translational modification modulates its interaction with target proteins, thereby precisely regulating carbon-nitrogen metabolic homeostasis and enabling adaptive nitrogen metabolism in response to host-derived nutrient cues. In this study, we found that glnK is upregulated during infection in a mouse pneumonia model. By growing bacteria in mouse bronchoalveolar lavage fluid (BALF), we demonstrated that the expression of glnK is activated by the NtrB-NtrC two-component regulatory system in response to the host nutrient environment. Mutation of glnK impairs bacterial virulence. Transcriptomic analysis revealed downregulation of the type III secretion system (T3SS) genes in the glnK mutant. Further studies revealed a role of GlnK in maintaining the homeostasis of the NtrB-NtrC system through a negative feedback mechanism, which is required for the expression of the T3SS genes. Collectively, these findings reveal a role of GlnK in interconnecting carbon–nitrogen balance and the T3SS in response to the host environment. Full article

Xanthomonas arboricola pv. pruni causes bacterial spot in peaches, a major disease affecting global Prunus production. Despite its economic significance, the virulence mechanisms that enable X. arboricola pv. pruni to colonize peach tissues and induce characteristic necrotic symptoms remain poorly understood. To identify key virulence determinants, a robust and reliable detached-leaf inoculation system was developed, and a genome-wide forward genetic screen of 2400 Tn5 mutants was conducted. A total of 34 mutants with consistently reduced virulence were identified, representing diverse functional categories including secretion systems, nutrient acquisition, primary metabolism, and regulatory pathways. The most prominent findings were the repeated identification of independent mutants in two type III effector genes, xopN and xopX, highlighting these effectors as central and nonredundant contributors to symptom induction. Mutants in the type III secretion system translocon-associated gene hrpF also showed virulence defects. Additional mutants affecting phosphate uptake (pstS), ammonium transport, and vitamin B₆ biosynthesis (pdxA, serC) revealed metabolic requirements essential for in planta fitness. Notably, several mutants reached bacterial population levels comparable to the wild-type isolate but produced little or no symptoms, indicating that bacterial multiplication and symptom development are not necessarily linked. This study provides the first comprehensive genome-wide functional screen of X. arboricola pv. pruni virulence and establishes a framework for dissecting infection mechanisms. The essential factors identified here, particularly XopN, XopX, and key metabolic pathways, represent promising targets for future anti-virulence strategies to manage bacterial spot disease. Characterizing the specific functions of each virulence factor identified in this study will be an important focus of future work. Full article