Pub Date : 2025-12-17DOI: 10.1016/j.micpath.2025.108240
Haiqin Wang, Yan Xu
Streptococcus pneumoniae continues to be a leading pathogen responsible for severe respiratory related diseases among children, often demanding prolonged treatment with antibiotics. In this study, we developed a chitosan-modified PLGA/alginate nanoparticles for controlled doxycycline delivery (CS-PLGA/Alginate@Doxy NPs) with the goal of improving therapeutic effect while reducing dosing frequency and treatment-related difficulties. The fabricated NPs demonstrated a well-defined spherical structure with an average diameter close to 50–70 nm, a stable negative surface charge, and a notably high drug encapsulation capability, confirming their suitability for inhalation-based antimicrobial therapy. In vitro drug release studies confirmed sustained Doxy release over 72 h under different pH conditions. Antibacterial activity was evaluated against of S. pneumoniae, showing significantly improved bactericidal activity compared to free Doxy and other combinations. Further, the crystal violet assay and fluorescent microscopy analysis reveals that, the S. pneumoniae biofilm thickness was significantly reduced with visible disintegration of EPS matrix when exposed to CS-PLGA/Alginate@Doxy NPs. Cytocompatibility assays on fibroblast (L929) and human lung epithelial cells (L-132) confirmed the safety profile of the CS-PLGA/Alginate@Doxy NPs for pediatric use. The results proposed that the fabricated CS-PLGA/Alginate@Doxy NPs signifies a promising targeted delivery platform for the effective management of pediatric pneumococcal infections.
{"title":"Development of chitosan-functionalized PLGA/alginate polymeric nanoparticles for controlled doxycycline release in pediatric Streptococcus pneumoniae infections","authors":"Haiqin Wang, Yan Xu","doi":"10.1016/j.micpath.2025.108240","DOIUrl":"10.1016/j.micpath.2025.108240","url":null,"abstract":"<div><div><em>Streptococcus pneumoniae</em> continues to be a leading pathogen responsible for severe respiratory related diseases among children, often demanding prolonged treatment with antibiotics. In this study, we developed a chitosan-modified PLGA/alginate nanoparticles for controlled doxycycline delivery (CS-PLGA/Alginate@Doxy NPs) with the goal of improving therapeutic effect while reducing dosing frequency and treatment-related difficulties. The fabricated NPs demonstrated a well-defined spherical structure with an average diameter close to 50–70 nm, a stable negative surface charge, and a notably high drug encapsulation capability, confirming their suitability for inhalation-based antimicrobial therapy. <em>In vitro</em> drug release studies confirmed sustained Doxy release over 72 h under different pH conditions. Antibacterial activity was evaluated against of <em>S. pneumoniae</em>, showing significantly improved bactericidal activity compared to free Doxy and other combinations. Further, the crystal violet assay and fluorescent microscopy analysis reveals that, the <em>S. pneumoniae</em> biofilm thickness was significantly reduced with visible disintegration of EPS matrix when exposed to CS-PLGA/Alginate@Doxy NPs. Cytocompatibility assays on fibroblast (L929) and human lung epithelial cells (L-132) confirmed the safety profile of the CS-PLGA/Alginate@Doxy NPs for pediatric use. The results proposed that the fabricated CS-PLGA/Alginate@Doxy NPs signifies a promising targeted delivery platform for the effective management of pediatric pneumococcal infections.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108240"},"PeriodicalIF":3.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.micpath.2025.108250
Verónica Rosales-Islas , J. Fernando Montes-García , Gerardo A. Ramírez-Paz-Y-Puente , Gloria Luz Paniagua-Contreras , José A. Gutiérrez-Pabello , Edgar Zenteno , Candelario Vázquez-Cruz , Erasmo Negrete-Abascal
Mannheimia haemolytica (Mh) is an opportunistic pathogen that causes pneumonic infections in different ruminants. It is also part of the respiratory tract microbiome, but it descends into the lower respiratory tract under stress, causing shipping fever. The stress hormones epinephrine and norepinephrine have been suggested to induce Mh biofilm dispersion, but their roles in virulence have not been shown. In this study, the effects of these two hormones on Mh growth and on the expression of adhesins, proteases, and biofilm formation are evaluated. Physiological concentrations (1–5 ng/mL) of epinephrine and norepinephrine increase the growth of Mh and the expression of 42- and 75-kDa gelatin proteases, induce biofilm dispersion, and decrease biofilm protein and carbohydrate concentrations. At 50 or 500 ng/mL concentrations of epinephrine and norepinephrine, the expression of OmpA and OmpH adhesins and 42- and 100-kDa casein proteases increases. Bacterial adhesion to bovine monocytes or oral epithelial cells also increases, but antibodies against OmpH and OmpA diminish adhesion. Our results strongly suggest that epinephrine and norepinephrine modulate the expression of Mh virulence factors.
{"title":"Epinephrine and norepinephrine increase the growth and expression of adhesins and proteases in Mannheimia haemolytica","authors":"Verónica Rosales-Islas , J. Fernando Montes-García , Gerardo A. Ramírez-Paz-Y-Puente , Gloria Luz Paniagua-Contreras , José A. Gutiérrez-Pabello , Edgar Zenteno , Candelario Vázquez-Cruz , Erasmo Negrete-Abascal","doi":"10.1016/j.micpath.2025.108250","DOIUrl":"10.1016/j.micpath.2025.108250","url":null,"abstract":"<div><div><em>Mannheimia haemolytica</em> (<em>Mh</em>) is an opportunistic pathogen that causes pneumonic infections in different ruminants. It is also part of the respiratory tract microbiome, but it descends into the lower respiratory tract under stress, causing shipping fever. The stress hormones epinephrine and norepinephrine have been suggested to induce <em>Mh</em> biofilm dispersion, but their roles in virulence have not been shown. In this study, the effects of these two hormones on <em>Mh</em> growth and on the expression of adhesins, proteases, and biofilm formation are evaluated. Physiological concentrations (1–5 ng/mL) of epinephrine and norepinephrine increase the growth of <em>Mh</em> and the expression of 42- and 75-kDa gelatin proteases, induce biofilm dispersion, and decrease biofilm protein and carbohydrate concentrations. At 50 or 500 ng/mL concentrations of epinephrine and norepinephrine, the expression of OmpA and OmpH adhesins and 42- and 100-kDa casein proteases increases. Bacterial adhesion to bovine monocytes or oral epithelial cells also increases, but antibodies against OmpH and OmpA diminish adhesion. Our results strongly suggest that epinephrine and norepinephrine modulate the expression of <em>Mh</em> virulence factors.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108250"},"PeriodicalIF":3.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.micpath.2025.108247
Anais L. Lucero-Olachea , Raúl O. Martínez-Rincón , Carmen Rodríguez-Jaramillo , Irais Ramírez-Sánchez , Bruno Gómez-Gil , Dariel Tovar-Ramírez , José Luis Balcázar , Eduardo Quiroz-Guzmán
Bacterial pathogens of the family Vibrionaceae are widespread in aquatic environments and pose a substantial threat to economically important fish species. In this study, we isolated and characterized a Vibrio diabolicus strain using whole-genome sequencing, which yielded a 5,039,696 bp genome distributed across two chromosomes: a larger chromosome (3,108,246 bp) and a smaller one (1,931,450 bp). The genome encoded multiple multidrug resistance genes and several virulence-associated factors, including the type III secretion system chaperone VcrH on the large chromosome and thermolabile hemolysin (tlh) on the smaller chromosome. Additional genes of interest present on the larger chromosome included clpA, clpS, clpX, clpP, two putative cas3 type I genes, and TnXax1, a Tn3 family transposase. Pathogenicity was assessed through a four-day intraperitoneal infection bioassay in juvenile Seriola rivoliana using bacterial concentrations of 1.4 × 101, 2.36 × 103, and 2.1 × 106 CFU/mL. Although no mortality was recorded, infected fish presented pronounced pathological alterations, including severe hemorrhages, muscle necrosis, granulomatous inflammation, and degeneration of intestinal tissues. Marked mucosal hyperplasia and increased infiltration of macrophages and lymphocytes were also observed in the intestine. Overall, these findings provide genomic and pathological insights into a V. diabolicus strain circulating in marine aquaculture systems and highlight its potential role as an emerging opportunistic pathogen capable of causing significant sublethal tissue damage despite limited mortality.
{"title":"Genomic characterization and pathological effects of Vibrio diabolicus in experimentally infected juvenile Seriola rivoliana","authors":"Anais L. Lucero-Olachea , Raúl O. Martínez-Rincón , Carmen Rodríguez-Jaramillo , Irais Ramírez-Sánchez , Bruno Gómez-Gil , Dariel Tovar-Ramírez , José Luis Balcázar , Eduardo Quiroz-Guzmán","doi":"10.1016/j.micpath.2025.108247","DOIUrl":"10.1016/j.micpath.2025.108247","url":null,"abstract":"<div><div>Bacterial pathogens of the family <em>Vibrionaceae</em> are widespread in aquatic environments and pose a substantial threat to economically important fish species. In this study, we isolated and characterized a <em>Vibrio diabolicus</em> strain using whole-genome sequencing, which yielded a 5,039,696 bp genome distributed across two chromosomes: a larger chromosome (3,108,246 bp) and a smaller one (1,931,450 bp). The genome encoded multiple multidrug resistance genes and several virulence-associated factors, including the type III secretion system chaperone <em>VcrH</em> on the large chromosome and thermolabile hemolysin (<em>tlh</em>) on the smaller chromosome. Additional genes of interest present on the larger chromosome included <em>clpA</em>, <em>clpS</em>, <em>clpX</em>, <em>clpP</em>, two putative cas3 type I genes, and TnXax1, a Tn3 family transposase. Pathogenicity was assessed through a four-day intraperitoneal infection bioassay in juvenile <em>Seriola rivoliana</em> using bacterial concentrations of 1.4 × 10<sup>1</sup>, 2.36 × 10<sup>3</sup>, and 2.1 × 10<sup>6</sup> CFU/mL. Although no mortality was recorded, infected fish presented pronounced pathological alterations, including severe hemorrhages, muscle necrosis, granulomatous inflammation, and degeneration of intestinal tissues. Marked mucosal hyperplasia and increased infiltration of macrophages and lymphocytes were also observed in the intestine. Overall, these findings provide genomic and pathological insights into a <em>V. diabolicus</em> strain circulating in marine aquaculture systems and highlight its potential role as an emerging opportunistic pathogen capable of causing significant sublethal tissue damage despite limited mortality.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108247"},"PeriodicalIF":3.5,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/j.micpath.2025.108246
Ashok Kumar , Abhishek Verma , V. Mahajan , Harbir Singh , G. Filia , Rajsukhbir Singh , Jagmeet Kaur , M.S. Bal
Peste des petits ruminants (PPR) is a highly contagious viral disease affecting sheep and goats, posing a significant threat to small ruminant health and rural livelihoods in Punjab, India. The objective of the present study was to investigate cases of per-acute mortality caused by Morbillivirus caprinae, which resulted in the death of 24.86 % (134/539) of animals across ten different sheep and goat farms. The overall morbidity, mortality and case fatality rate were observed during the outbreak investigation. However, necropsy and histopathological findings were strongly indicative of Morbillivirus caprinae infection in domestic small ruminants. The presence of PPRV was confirmed through Sandwich ELISA and one-step RT-PCR assays. The study also investigated potential interspecies transmission between goats and sheep in mixed flocks during a recent PPR outbreak. Genetic analysis of samples from affected flocks in neighboring regions revealed close similarity with other Asian PPRV isolates, indicating possible regional viral circulation.
Phylogenetic analysis based on the nucleocapsid (N) protein gene revealed that the virus belonged to Lineage IV and was detected in samples from infected sheep, domestic goats, and animals from mixed farms. These findings suggest the likely spread of Lineage IV PPRV strains within the small ruminant population in the region, potentially originating from domestic goats.
{"title":"Clinicopathological and molecular characterization of Morbillivirus caprinae Lineage IV in PPR outbreak among small ruminants of Punjab","authors":"Ashok Kumar , Abhishek Verma , V. Mahajan , Harbir Singh , G. Filia , Rajsukhbir Singh , Jagmeet Kaur , M.S. Bal","doi":"10.1016/j.micpath.2025.108246","DOIUrl":"10.1016/j.micpath.2025.108246","url":null,"abstract":"<div><div>Peste des petits ruminants (PPR) is a highly contagious viral disease affecting sheep and goats, posing a significant threat to small ruminant health and rural livelihoods in Punjab, India. <strong>The objective of the present study was to investigate cases of per-acute mortality caused by <em>Morbillivirus caprinae</em>, which resulted in the death of 24.86 % (134/539) of animals across ten different sheep and goat farms.</strong> The overall morbidity, mortality and case fatality rate were observed during the outbreak investigation. However, necropsy and histopathological findings were strongly indicative of <em>Morbillivirus caprinae</em> infection in domestic small ruminants. The presence of PPRV was confirmed through Sandwich ELISA and one-step RT-PCR assays. The study also investigated potential interspecies transmission between goats and sheep in mixed flocks during a recent PPR outbreak. Genetic analysis of samples from affected flocks in neighboring regions revealed close similarity with other Asian PPRV isolates, indicating possible regional viral circulation.</div><div>Phylogenetic analysis based on the nucleocapsid (N) protein gene revealed that the virus belonged to Lineage IV and was detected in samples from infected sheep, domestic goats, and animals from mixed farms. These findings suggest the likely spread of Lineage IV PPRV strains within the small ruminant population in the region, potentially originating from domestic goats.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108246"},"PeriodicalIF":3.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-14DOI: 10.1016/j.micpath.2025.108245
J. Harish , M.K. Prasannakumar , R. Karan , B.P. Maruthi Prasad , K.N. Pallavi , H.C. Lohithaswa , G. Punith , Noor Ayesha
Maize stalk rot is a major constraint to crop productivity, caused by a complex of Fusarium species. This study investigated the diversity, genetic structure and host-pathogen interactions associated with stalk rot in Indian maize. Phylogenetic analysis of isolates collected during 2022–2023 identified species from three major complexes: Fusarium fujikuroi (FFSC), F. incarnatum-equiseti (FIESC) and F. solani (FSSC), with F. verticillioides being the predominant pathogen. Genetic analysis using ITS, TEF-1α and RPB-2 markers revealed high within-population variability and moderate differentiation across populations. DNA polymorphism and neutrality tests suggested intense selection pressures and population expansion events, especially at the TEF-1α and ITS loci. Transcriptomic analysis of infected maize revealed 6948 differentially expressed genes. Upregulated genes were associated with fungal recognition, cell wall degradation and antimicrobial compound production, while downregulated genes indicated suppression of photosynthesis, protein folding and cytoskeletal functions. KEGG enrichment analysis highlighted significant changes in pathways related to lipid metabolism, secondary metabolite biosynthesis, oxidative stress and energy reallocation. Biochemical assays confirmed the elevated activity of plant cell wall-degrading enzymes (cellulase, β-glucosidase and pectate lyase), peaking at 4–6 days post-infection, supporting their role in tissue maceration. LC-MS/MS-based metabolite profiling revealed a clear metabolic shift in infected maize, characterized by an increased accumulation of secondary metabolites, including flavonoid glycosides and phenylpropanoids, in contrast to the dominance of primary metabolism in healthy tissues. These results provide a comprehensive understanding of the genetic, biochemical and metabolic responses of maize to stalk rot, underscoring the need for management and resistance breeding strategies targeting diverse Fusarium species.
{"title":"Genetic diversity, haplotyping, integrative transcriptomic and metabolomic insights in Fusarium stalk rot of maize","authors":"J. Harish , M.K. Prasannakumar , R. Karan , B.P. Maruthi Prasad , K.N. Pallavi , H.C. Lohithaswa , G. Punith , Noor Ayesha","doi":"10.1016/j.micpath.2025.108245","DOIUrl":"10.1016/j.micpath.2025.108245","url":null,"abstract":"<div><div>Maize stalk rot is a major constraint to crop productivity, caused by a complex of <em>Fusarium</em> species. This study investigated the diversity, genetic structure and host-pathogen interactions associated with stalk rot in Indian maize. Phylogenetic analysis of isolates collected during 2022–2023 identified species from three major complexes: <em>Fusarium fujikuroi</em> (FFSC), <em>F. incarnatum</em>-<em>equiseti</em> (FIESC) and <em>F. solani</em> (FSSC), with <em>F. verticillioides</em> being the predominant pathogen. Genetic analysis using ITS, <em>TEF-1α</em> and <em>RPB-2</em> markers revealed high within-population variability and moderate differentiation across populations. DNA polymorphism and neutrality tests suggested intense selection pressures and population expansion events, especially at the <em>TEF-1α</em> and ITS loci. Transcriptomic analysis of infected maize revealed 6948 differentially expressed genes. Upregulated genes were associated with fungal recognition, cell wall degradation and antimicrobial compound production, while downregulated genes indicated suppression of photosynthesis, protein folding and cytoskeletal functions. KEGG enrichment analysis highlighted significant changes in pathways related to lipid metabolism, secondary metabolite biosynthesis, oxidative stress and energy reallocation. Biochemical assays confirmed the elevated activity of plant cell wall-degrading enzymes (cellulase, β-glucosidase and pectate lyase), peaking at 4–6 days post-infection, supporting their role in tissue maceration. LC-MS/MS-based metabolite profiling revealed a clear metabolic shift in infected maize, characterized by an increased accumulation of secondary metabolites, including flavonoid glycosides and phenylpropanoids, in contrast to the dominance of primary metabolism in healthy tissues. These results provide a comprehensive understanding of the genetic, biochemical and metabolic responses of maize to stalk rot, underscoring the need for management and resistance breeding strategies targeting diverse <em>Fusarium</em> species.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108245"},"PeriodicalIF":3.5,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-13DOI: 10.1016/j.micpath.2025.108242
Muhammad Bilal Habib , Maryam Aftab , Afreenish Amir , Faheem Ullah , Naseer Ali Shah , Fatima Javed , Nadhirah Mohamad Zain , Aamer Ikram , Muhammad Kamran , Mamoon Ur Rasheed
Background/objectives
Treatment failure and increased death rates may arise from the presence of drug-resistant microorganisms in the hospital environment. The purpose of this study was to devise new therapeutic hydrogel formulations to target drug resistant bacteria.
Methodology
In this study injectable hydrogel was developed containing Chitosan (CH) Methacrylic acid (MAA) and Glutaraldehyde, via polymerization technique, with subsequent loading of Iron oxide nanoparticles (IONPs) and Colistin (CT). Physicochemical characterization was performed by UV–Vis spectroscopy, zeta sizer, Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Energy Dispersive X-ray Spectroscopy (EDX), and Scanning Electron Microscopy (SEM) and drug release assays were conducted to predict the hydrogel's injectable therapeutic applications. Molecular Docking, simulation analysis was performed to evaluate the binding affinities of hydrogel components to their respective target. A broth microdilution method was employed to assess the antibacterial and antibiofilm efficacy.
Results
The CH-MAA hydrogel showed remarkable swelling, excellent biodegradability, and cytocompatibility. The hydrogels followed non-Fickian drug release indicated by the computed "n" values of 0.45–0.89. The CH-MAA hydrogel showed excellent antibacterial effects with a significant decrease in MIC values (5 μg/mL). The IONPs loaded hydrogels showed significant decrease in MIC value (0.78 μg/mL) as compared to IONP standalone (50 μg/mL). CT resistant A. baumannii was successfully targeted by CT loaded hydrogel which showed a remarkable MIC (1.25 μg/mL).
Conclusions
Current findings suggest that the newly designed CH-MAA injectable hydrogel could be a novel therapeutic agent with antibacterial and antibiofilm activity against these highly resistant bacteria to combat AMR.
{"title":"Development and characterization of dual-functional polymeric hydrogels: A Sustainable approach for drug delivery and antimicrobial applications","authors":"Muhammad Bilal Habib , Maryam Aftab , Afreenish Amir , Faheem Ullah , Naseer Ali Shah , Fatima Javed , Nadhirah Mohamad Zain , Aamer Ikram , Muhammad Kamran , Mamoon Ur Rasheed","doi":"10.1016/j.micpath.2025.108242","DOIUrl":"10.1016/j.micpath.2025.108242","url":null,"abstract":"<div><h3>Background/objectives</h3><div>Treatment failure and increased death rates may arise from the presence of drug-resistant microorganisms in the hospital environment. The purpose of this study was to devise new therapeutic hydrogel formulations to target drug resistant bacteria.</div></div><div><h3>Methodology</h3><div>In this study injectable hydrogel was developed containing Chitosan (CH) Methacrylic acid (MAA) and Glutaraldehyde, via polymerization technique, with subsequent loading of Iron oxide nanoparticles (IONPs) and Colistin (CT). Physicochemical characterization was performed by UV–Vis spectroscopy, zeta sizer, Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Energy Dispersive X-ray Spectroscopy (EDX), and Scanning Electron Microscopy (SEM) and drug release assays were conducted to predict the hydrogel's injectable therapeutic applications. Molecular Docking, simulation analysis was performed to evaluate the binding affinities of hydrogel components to their respective target. A broth microdilution method was employed to assess the antibacterial and antibiofilm efficacy.</div></div><div><h3>Results</h3><div>The CH-MAA hydrogel showed remarkable swelling, excellent biodegradability, and cytocompatibility. The hydrogels followed non-Fickian drug release indicated by the computed \"n\" values of 0.45–0.89. The CH-MAA hydrogel showed excellent antibacterial effects with a significant decrease in MIC values (5 μg/mL). The IONPs loaded hydrogels showed significant decrease in MIC value (0.78 μg/mL) as compared to IONP standalone (50 μg/mL). CT resistant <em>A. baumannii</em> was successfully targeted by CT loaded hydrogel which showed a remarkable MIC (1.25 μg/mL).</div></div><div><h3>Conclusions</h3><div>Current findings suggest that the newly designed CH-MAA injectable hydrogel could be a novel therapeutic agent with antibacterial and antibiofilm activity against these highly resistant bacteria to combat AMR.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108242"},"PeriodicalIF":3.5,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.1016/j.micpath.2025.108244
Vidya Manju , Mahmoud Bayoumi , Muhammad Munir
N6-methyladenosine (m6A) is one of the most prevalent and dynamic internal RNA modifications, playing a crucial role in regulating gene expression and cancer progression. This epitranscriptomic mark is co-transcriptionally deposited by m6A writers, recognised by reader proteins, and removed by erasers. In recent years, a wide range of viruses have been shown to carry m6A modifications within their RNA genomes or transcripts, which interact with the host cell's m6A machinery to influence the viral life cycle. The field of viral epitranscriptomics has emerged to explore how such modifications impact viral gene expression, replication, and the evasion or modulation of host immune responses. Notably, m6A marks can enhance viral RNA stability through interaction with YTHDF2, a major m6A reader protein. Interest in YTHDF2 has grown due to its roles in RNA metabolism, disease progression, and therapeutic potential. However, its effect on viral replication is complex and context-dependent, exhibiting both proviral and antiviral functions under different cellular environments. This review highlights current insights into how YTHDF2 modulates the replication of various viruses and discusses its broader implications in host–virus interactions.
{"title":"Epitranscriptomic control of viral infection: YTHDF2 at the crossroads of host–virus interactions","authors":"Vidya Manju , Mahmoud Bayoumi , Muhammad Munir","doi":"10.1016/j.micpath.2025.108244","DOIUrl":"10.1016/j.micpath.2025.108244","url":null,"abstract":"<div><div>N6-methyladenosine (m6A) is one of the most prevalent and dynamic internal RNA modifications, playing a crucial role in regulating gene expression and cancer progression. This epitranscriptomic mark is co-transcriptionally deposited by m6A writers, recognised by reader proteins, and removed by erasers. In recent years, a wide range of viruses have been shown to carry m6A modifications within their RNA genomes or transcripts, which interact with the host cell's m6A machinery to influence the viral life cycle. The field of viral epitranscriptomics has emerged to explore how such modifications impact viral gene expression, replication, and the evasion or modulation of host immune responses. Notably, m6A marks can enhance viral RNA stability through interaction with YTHDF2, a major m6A reader protein. Interest in YTHDF2 has grown due to its roles in RNA metabolism, disease progression, and therapeutic potential. However, its effect on viral replication is complex and context-dependent, exhibiting both proviral and antiviral functions under different cellular environments. This review highlights current insights into how YTHDF2 modulates the replication of various viruses and discusses its broader implications in host–virus interactions.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108244"},"PeriodicalIF":3.5,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.micpath.2025.108237
Wellars Twahirwa , Patrick Nemeyimana , Xavier Nyandwi , Jean D'Amour Iradukunda , Jean Felix Muneza , Philbert Kanimba , Khadijat O. Adefaye , Noel Gahamanyi , Nadine Rujeni
Background
Intestinal parasitic infections (IPIs) are a public health issue affecting young children in low and middle income countries (LMICs). These factors may induce malnutrition, as well as systemic and/or intestinal inflammation, depending on the species, intensity of infection, and host response. This study aimed at determining the effect of intestinal parasites on nutritional status and inflammatory responses in pre- and school-aged children in rural areas of the southern province of Rwanda.
Methods
A cross-sectional study involving 127 children under 12 years of age was conducted at two health centers in Huye District, Southern Province, Rwanda, from January to February 2022. A structured questionnaire was used to collect sociodemographic information, feeding habits, anthropometric measurements, and information on infection/malnutrition risk factors. Stool samples were collected to test for intestinal parasites by using microscope, while serum was collected to measure (anti)inflammatory markers [interleukin-10 (IL-10), tumour necrosis factor-alpha (TNF-α), total protein, and C-reactive protein (CRP)].
Results
The overall prevalence of IPIs was 38.6 %, with Entamoeba coli being the most prevalent (21.3 %), Q1: Although E. coli is non-pathogenic, its high prevalence serves as an indicator of fecal–oral contamination and poor environmental sanitation. Thus, it reflects the same exposure pathways responsible for pathogenic intestinal parasites. Its detection therefore signals ongoing transmission risks and inadequate hygiene conditions that contribute to the overall public health burden. followed by Ascaris lumbricoides (18.1 %), Entamoeba histolytica (11.8 %), and Trichuris trichiura (1.6 %). Coinfections accounted for 12.6 % of the infections. Moreover, 48.0 %, 25.2 %, and 9.4 % of the children were stunted, underweight, and stunted, respectively. Underweight, IL-10, and total protein levels were significantly associated with IPIs. Our findings also indicated that food supplements had a significant positive effect on stunting.
Conclusion
Ascaris lumbricoides, Entamoeba histolytica, and Trichuris trichiura were the predominant parasites. Intestinal parasitic infections in preschool children and schoolchildren affect the nutritional status, possibly through chronic inflammation. Further mechanistic investigations will shed more light on the regulation of the inflammatory response.
{"title":"Intestinal parasitic infections associated with nutritional status and inflammatory markers among young children in Huye district, Rwanda","authors":"Wellars Twahirwa , Patrick Nemeyimana , Xavier Nyandwi , Jean D'Amour Iradukunda , Jean Felix Muneza , Philbert Kanimba , Khadijat O. Adefaye , Noel Gahamanyi , Nadine Rujeni","doi":"10.1016/j.micpath.2025.108237","DOIUrl":"10.1016/j.micpath.2025.108237","url":null,"abstract":"<div><h3>Background</h3><div>Intestinal parasitic infections (IPIs) are a public health issue affecting young children in low and middle income countries (LMICs). These factors may induce malnutrition, as well as systemic and/or intestinal inflammation, depending on the species, intensity of infection, and host response. This study aimed at determining the effect of intestinal parasites on nutritional status and inflammatory responses in pre- and school-aged children in rural areas of the southern province of Rwanda.</div></div><div><h3>Methods</h3><div>A cross-sectional study involving 127 children under 12 years of age was conducted at two health centers in Huye District, Southern Province, Rwanda, from January to February 2022. A structured questionnaire was used to collect sociodemographic information, feeding habits, anthropometric measurements, and information on infection/malnutrition risk factors. Stool samples were collected to test for intestinal parasites by using microscope, while serum was collected to measure (anti)inflammatory markers [interleukin-10 (IL-10), tumour necrosis factor-alpha (TNF-α), total protein, and C-reactive protein (CRP)].</div></div><div><h3>Results</h3><div>The overall prevalence of IPIs was 38.6 %, with <em>Entamoeba coli</em> being the most prevalent (21.3 %), Q1: Although <em>E. coli</em> is non-pathogenic, its high prevalence serves as an indicator of fecal–oral contamination and poor environmental sanitation. Thus, it reflects the same exposure pathways responsible for pathogenic intestinal parasites. Its detection therefore signals ongoing transmission risks and inadequate hygiene conditions that contribute to the overall public health burden. followed by <em>Ascaris lumbricoides</em> (18.1 %), <em>Entamoeba histolytica</em> (11.8 %), and <em>Trichuris trichiura</em> (1.6 %). Coinfections accounted for 12.6 % of the infections. Moreover, 48.0 %, 25.2 %, and 9.4 % of the children were stunted, underweight, and stunted, respectively. Underweight, IL-10, and total protein levels were significantly associated with IPIs. Our findings also indicated that food supplements had a significant positive effect on stunting.</div></div><div><h3>Conclusion</h3><div><em>Ascaris lumbricoides</em>, <em>Entamoeba histolytica</em>, and <em>Trichuris trichiura</em> were the predominant parasites. Intestinal parasitic infections in preschool children and schoolchildren affect the nutritional status, possibly through chronic inflammation. Further mechanistic investigations will shed more light on the regulation of the inflammatory response.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108237"},"PeriodicalIF":3.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.micpath.2025.108239
Emi Tanaka , Takeaki Wajima , Kei-ichi Uchiya
Streptococcus pneumoniae is a major respiratory pathogen and a commensal bacterium of the nasopharynx. However, it remains unclear how commensal S. pneumoniae switches to a pathogenic form. Recently, a 3D human lung tissue model was established and adopted as a bacterial infection model. Here, we analysed the effects of commensal bacteria on the pathogenicity of S. pneumoniae in human tissues using a model constructed by interstitial layer of human fibroblasts mixed with collagen and an epithelial layer of layered human lung epithelial cells. When S. pneumoniae infected to the model, severe injury to the epithelial layer and interleukin-1β production were observed. Conversely, these inflammatory reactions were suppressed by co-infection with Haemophilus influenzae, without killing S. pneumoniae. Immunofluorescence staining showed that during co-infection, S. pneumoniae did not invade and remained on the surface of the epithelial layer. Notably, the suppression of epithelium injury was specifically attributed to the presence of H. influenzae, and the constant coexistence of both living bacteria was crucial for maintaining normal lung tissue. Conclusively, these findings indicate that a well-balanced coexistence of S. pneumoniae with H. influenzae and is essential for maintaining healthy lung tissues.
{"title":"Protective role of Haemophilus influenzae in Streptococcus pneumoniae-induced epithelium injury","authors":"Emi Tanaka , Takeaki Wajima , Kei-ichi Uchiya","doi":"10.1016/j.micpath.2025.108239","DOIUrl":"10.1016/j.micpath.2025.108239","url":null,"abstract":"<div><div><em>Streptococcus pneumoniae</em> is a major respiratory pathogen and a commensal bacterium of the nasopharynx. However, it remains unclear how commensal <em>S. pneumoniae</em> switches to a pathogenic form. Recently, a 3D human lung tissue model was established and adopted as a bacterial infection model. Here, we analysed the effects of commensal bacteria on the pathogenicity of <em>S. pneumoniae</em> in human tissues using a model constructed by interstitial layer of human fibroblasts mixed with collagen and an epithelial layer of layered human lung epithelial cells. When <em>S. pneumoniae</em> infected to the model, severe injury to the epithelial layer and interleukin-1β production were observed. Conversely, these inflammatory reactions were suppressed by co-infection with <em>Haemophilus influenzae</em>, without killing <em>S. pneumoniae</em>. Immunofluorescence staining showed that during co-infection, <em>S. pneumoniae</em> did not invade and remained on the surface of the epithelial layer. Notably, the suppression of epithelium injury was specifically attributed to the presence of <em>H. influenzae</em>, and the constant coexistence of both living bacteria was crucial for maintaining normal lung tissue. Conclusively, these findings indicate that a well-balanced coexistence of <em>S. pneumoniae</em> with <em>H. influenzae</em> and is essential for maintaining healthy lung tissues.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108239"},"PeriodicalIF":3.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10DOI: 10.1016/j.micpath.2025.108236
Juan Wu , Mei Shi , Lin Zhu, Xin Zheng, Chunjie Liao, Rui-Rui Peng, Fu-Quan Long
MicroRNAs, particularly miR-330-3p, are fundamentally involved in many infectious diseases and the host's response to pathogen attacks, with previous studies noting increased miR-330-3p levels in neurosyphilis patients' PBMCs compared to healthy controls. The detailed biological functions and mechanisms of miR-330-3p in neurosyphilis, however, remain poorly defined. Our research confirms elevated miR-330-3p expression in CD4+ T cells of neurosyphilis patients, correlating significantly with T cell ferroptosis. Using bioinformatic predictions and in vitro cell experiments, including gene overexpression, silencing, and ac4C dot plot, in human Jurkat-E6-1 and primary CD4+ T cell, we have shown that miR-330-3p binds to the 3′UTR of NAT10 mRNA, overexpression of miR-330-3p could significantly suppress NAT10 expression, which in turn leads to decreased acetylation of GPX4 mRNA and increased T cell ferroptosis due to reduced glutathione peroxidase activity. Overexpression of NAT10 or activation of GPX4 Glutathione Peroxidase activity could obviously reverse the elevated T cell ferroptosis induced by miR-330-3p overexpression. Additionally, our findings demonstrate that miR-330-3p enhances IFN-γ production in a NAT10-independent manner. These results unveil a novel mechanism through which miR-330-3p promotes T cell ferroptosis and IFN-γ production in neurosyphilis.
{"title":"MiR-330-3p promotes T cell ferroptosis and IFN-γ production via targeting NAT10 in neurosyphilis","authors":"Juan Wu , Mei Shi , Lin Zhu, Xin Zheng, Chunjie Liao, Rui-Rui Peng, Fu-Quan Long","doi":"10.1016/j.micpath.2025.108236","DOIUrl":"10.1016/j.micpath.2025.108236","url":null,"abstract":"<div><div>MicroRNAs, particularly miR-330-3p, are fundamentally involved in many infectious diseases and the host's response to pathogen attacks, with previous studies noting increased miR-330-3p levels in neurosyphilis patients' PBMCs compared to healthy controls. The detailed biological functions and mechanisms of miR-330-3p in neurosyphilis, however, remain poorly defined. Our research confirms elevated miR-330-3p expression in CD4<sup>+</sup> T cells of neurosyphilis patients, correlating significantly with T cell ferroptosis. Using bioinformatic predictions and <em>in vitro</em> cell experiments, including gene overexpression, silencing, and ac4C dot plot, in human Jurkat-E6-1 and primary CD4<sup>+</sup> T cell, we have shown that miR-330-3p binds to the 3′UTR of NAT10 mRNA, overexpression of miR-330-3p could significantly suppress NAT10 expression, which in turn leads to decreased acetylation of <em>GPX4</em> mRNA and increased T cell ferroptosis due to reduced glutathione peroxidase activity. Overexpression of NAT10 or activation of GPX4 Glutathione Peroxidase activity could obviously reverse the elevated T cell ferroptosis induced by miR-330-3p overexpression. Additionally, our findings demonstrate that miR-330-3p enhances IFN-γ production in a NAT10-independent manner. These results unveil a novel mechanism through which miR-330-3p promotes T cell ferroptosis and IFN-γ production in neurosyphilis.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108236"},"PeriodicalIF":3.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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