Microbial pathogenesis最新文献

{"title":"First isolation and characterization of caprine parainfluenza virus type 3 from cattle in China","authors":"Yao Zhang ,&nbsp;Kaicheng Wang ,&nbsp;Youyi Lu ,&nbsp;Xuwen Li ,&nbsp;Wenliang Li ,&nbsp;Zihao Pan ,&nbsp;Huochun Yao","doi":"10.1016/j.micpath.2025.108061","DOIUrl":"10.1016/j.micpath.2025.108061","url":null,"abstract":"<div><div>Caprine parainfluenza virus type 3 (CPIV3) is an enveloped single-stranded negative-sense RNA virus, commonly found in respiratory tract infections of goats and sheep. However, there have been no reports of CPIV3 infection in cattle. In this study, a strain of CPIV3 named HB2304S3 was isolated from a cattle with respiratory symptoms using Madin-Darby bovine kidney cells. The strain was verified by PCR and high-throughput sequencing, and the complete genomic sequence was obtained. After purification of the virus, hemagglutination tests and physicochemical property tests were conducted on this CPIV3 strain. The hemagglutination titer of the isolate was 1:40, and it was sensitive to ether, trypsin, temperature, and pH. To further investigate CPIV3 epidemiology in Chinese cattle populations, we conducted molecular surveillance across multiple provinces. The results revealed that 52 samples were positive for CPIV3, with a total positive rate of 34.21 % (52/152). Moreover, CPIV3 was detected in 12 cattle farms, with a farm positive rate of 70.59 % (12/17). These findings provide the first conclusive evidence of CPIV3 cross-species transmission to cattle and reveal its significant prevalence within cattle populations in China.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108061"},"PeriodicalIF":3.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137951","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}

{"title":"Advance Helicobacter pylori eradication: Current therapeutic strategies and the potential of lipid-based nanocarriers for targeting receptors","authors":"Mohamed Sharaf ,&nbsp;Tehsin Ullah Khan ,&nbsp;Chen-Guang Liu","doi":"10.1016/j.micpath.2025.108060","DOIUrl":"10.1016/j.micpath.2025.108060","url":null,"abstract":"<div><div><em>Helicobacter pylori</em> (<em>H. pylori</em>) is a Gram-negative bacteria microaerophilic, and spiral-shaped. <em>H. pylori</em> infection remains one of the most difficult challenges, resulting in chronic gastritis and peptic ulcers, increasing the mortality rate due to stomach cancer, exposed to more than 90 % worldwide. New treatment strategies are urgently needed to improve current advances in modern medicine. The lipid-based nanocarrier gained the advantages of drug encapsulation and high retention time in the stomach with the drug release rate for long periods and targeting <em>H. pylori</em> site infection accurately, with more than one strategy. This review article discusses bacterial pathogenesis, virulence mechanism of bacterial infection, and current different therapeutic effectiveness of fighting <em>H. pylori</em> infections. Moreover, this review provides an overview of how to use the novel designs of drugs-loaded lipid micro and nano delivery systems prepared through various biomaterials and natural processes to combat <em>H. pylori</em> infection through impact gastro-maintenance properties, discharge rates, which contributes to the perfection of therapeutic approaches. Moreover, combinatory studies of lipid-based nanocarrier have proven efficiency against <em>H. pylori</em> infection, with an advantage of lower cytotoxicity, minimal side effects, and stronger antibacterial potential. This review will have potential contribution in combating infectious pathogens using lipid-based nano delivery systems.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108060"},"PeriodicalIF":3.5,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131310","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}

{"title":"Antimicrobial, antioxidant, wound healing, and cytotoxic effects of maggot extract from molecularly identified Chrysomya albiceps (Diptera: Calliphoridae)","authors":"Ghada E. Dawwam ,&nbsp;Abdelwahab A. Ibrahim ,&nbsp;Ramy E. El-Ansary ,&nbsp;Abeer H.A. Abdelhafiz ,&nbsp;Aya S. Omara ,&nbsp;Abla D. Abdel-Meguid ,&nbsp;Mohamed M. Baz","doi":"10.1016/j.micpath.2025.108056","DOIUrl":"10.1016/j.micpath.2025.108056","url":null,"abstract":"<div><div>The medical industry is currently experiencing a deficit of effective therapies to prevent infections, as the evolution of multidrug resistance has outpaced the research and development of new effective medications. Blowfly maggots have attracted high interest for their medicinal and therapeutic potential. This study was conducted to assess the antibacterial efficacy of <em>Chrysomya albiceps</em> larval extract against four multidrug-resistant pathogenic bacteria, including Gram-positive (<em>Listeria monocytogenes</em> ATCC 19155 and <em>Staphylococcus aureus</em> ATCC 43300) and Gram-negative bacteria (<em>Escherichia coli</em> ATCC 8739 and <em>Salmonella</em> sp. ATCC 14028). The extract strongly inhibited all tested bacterial species with inhibition zones ranging from 18 to 25 mm, showing the highest effect on <em>S. aureus</em>. Additionally, the extract exhibited potent antioxidant activity with an IC₅₀ of 44.89 μg/mL and was non-toxic to human fibroblast (HFB4) cells up to 250 μg/mL. In vitro wound healing assays demonstrated that the extract significantly accelerated wound closure within 48 h. GC-MS analysis identified 17 bioactive compounds, most with known antimicrobial properties. Molecular docking studies confirmed stable interactions between these compounds and key bacterial protein targets, supporting the observed bioactivity. As part of the genetic diversity, larval samples were identified by nucleotide sequencing of the mitochondrial cytochrome <em>c</em> oxidase subunit I (COXI gene). These results were then compared with similar sequences that had already been put in GenBank. Moreover, a molecular docking study was performed to confirm and rationalize the observed biological activity. Overall, these results suggest that <em>C. albiceps</em> larval extract possesses antibacterial, antioxidant, and wound-healing activities and represents a safe, natural candidate for developing novel pharmaceutical and therapeutic agents.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108056"},"PeriodicalIF":3.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125046","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}

{"title":"Effect of lauric acid on efflux pump inhibition in Staphylococcus aureus K2068: Regulation of the mepA gene and membrane permeability alterations","authors":"Zildene de Sousa Silveira ,&nbsp;Nair Silva Macêdo ,&nbsp;Cristina Rodrigues dos Santos Barbosa ,&nbsp;Ana Carolina Ferreira Araujo ,&nbsp;Gustavo Marinho Miranda ,&nbsp;João Arthur de Oliveira Borges ,&nbsp;Cícera Datiane de Morais Oliveira-Tintino ,&nbsp;Saulo Relison Tintino ,&nbsp;João Victor de Oliveira Alves ,&nbsp;Maria Tereza dos Santos Correia ,&nbsp;Emmanuel Silva Marinho ,&nbsp;Hélcio Silva dos Santos ,&nbsp;Matheus Nunes da Rocha ,&nbsp;Marcia Machado Marinho ,&nbsp;Henrique Douglas Melo Coutinho ,&nbsp;Francisco Assis Bezerra da Cunha ,&nbsp;Márcia Vanusa da Silva","doi":"10.1016/j.micpath.2025.108057","DOIUrl":"10.1016/j.micpath.2025.108057","url":null,"abstract":"<div><div>MepA efflux protein found in <em>Staphylococcus aureus</em> belongs to the MATE (Multidrug and Toxic Compound Extrusion) family and plays an important role in bacterial resistance. We investigated the potential of lauric acid as an inhibitor of the MepA efflux pump by means of Minimum Inhibitory Concentration (MIC) assays and modulation of the MICs of ciprofloxacin and ethidium bromide (EtBr) against <em>S. aureus</em>; the compound's ability to increase the fluorescence of EtBr and Sytox Green, as well as its ability to inhibit the expression of the <em>mepA</em> gene. The results showed that lauric acid had no antibacterial effect against <em>S. aureus</em> K2068. When combined with ciprofloxacin, the compound potentiated the effect of the antibiotic, reducing the MIC from 64 to 32 μg/mL and increasing the fluorescence of EtBr and Sytox Green, suggesting inhibition of MepA and greater permeabilization of the cell membrane. Furthermore, qPCR assays revealed that lauric acid promoted a reduction in <em>mepA</em> gene expression. Molecular docking indicated that lauric acid interacts with the efflux pump in a similar way to chlorpromazine through hydrophobic interaction with the Phe153 residue. ADME modeling suggested that lauric acid's moderate lipophilicity favors passive cell permeability. The results of the toxicity assays in <em>D. melanogaster</em> indicate that lauric acid and ciprofloxacin exhibit low toxicity in the evaluated model. Together, these findings suggest that lauric acid could be a promising antibiotic adjuvant and MepA efflux pump inhibitor in <em>S. aureus.</em></div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108057"},"PeriodicalIF":3.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113664","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}

{"title":"Immunological aspects of mucosal vaccine-based bacterial-like particles (BLPs) – An updated review","authors":"T.D. Phuong Nguyen ,&nbsp;P. Thuan Cu ,&nbsp;Teerajet Laohasatian ,&nbsp;Thu-Dung Doan","doi":"10.1016/j.micpath.2025.108055","DOIUrl":"10.1016/j.micpath.2025.108055","url":null,"abstract":"<div><div>Mucosal vaccine-based Bacterium-like particles (BLP) adjuvants are recognised for their safety, ease of preparation, excellent stability, and efficient delivery to mucosal surfaces. Remarkable progress has been achieved in the development of BLP-based mucosal vaccines. This review aims to provide a comprehensive understanding of the current application of BLP adjuvants in vaccine development, focusing on their efficacy, effectiveness, and mechanisms of adjuvanticity. Specifically, this review highlights the promising potential of BLP as a mucosal adjuvant to elicit protective and immune responses. The information presented will offer updated and thorough insights into the application of BLP in vaccination strategies for a wide range of hosts. Additionally, this review discusses the potential benefits and challenges associated with BLP adjuvants, aiming to provide valuable suggestions for future research and vaccine design efforts.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108055"},"PeriodicalIF":3.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113704","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}

{"title":"Effects of probiotics on gut microbiota in diarrheal Chinese pangolins (Manis pentadactyla) analyzed through 16S rRNA sequencing","authors":"Lina Zhang ,&nbsp;Qihui Li ,&nbsp;Yan Hua","doi":"10.1016/j.micpath.2025.108036","DOIUrl":"10.1016/j.micpath.2025.108036","url":null,"abstract":"<div><div>The gut microbiota plays important roles in intestinal health, but the changes and functions of microbiota in diarrheal pangolins remain poorly understood. This study analyzed gut microbiota changes in 12 Chinese pangolins (<em>Manis pentadactyla</em>) from diarrhea to recovery using <em>16S rRNA</em> amplicon sequencing. Fecal samples of Chinese pangolins were achieved at day 1 (diarrhea) and day 5 (post-probiotic treatment). Results showed significantly increased microbial diversity and structural shifts in gut microbiota following probiotics treatment. A total of 18 phyla were identified in the fecal microorganisms of Chinese pangolins. <em>Firmicutes</em>, <em>Proteobacteria</em>, <em>Bacteroidetes</em>, and <em>Fusobacteria</em> were predominant bacteria. At the genus level, <em>Clostridium_sensu_stricto_1</em>, <em>Bacteroides</em>, <em>Clostridium</em>, <em>Streptococcus</em>, <em>Escherichia-Shigella</em>, <em>Megasphaera</em>, <em>Cellulosilyticum,</em> and <em>Lactococcus</em> were the predominant in both diarrheal groups and recovery group. After probiotic treatment, <em>Streptococcus</em> (<em>P</em> = 0.00001), and <em>Escherichia-Shigella</em> (<em>P</em> = 0.04) were significantly decreased<em>,</em> and similar phenomenon was observed in <em>Limosilactobacillus</em> (<em>P</em> = 0.0003) and <em>Lactobacillus</em> (<em>P</em> = 0.0002). In conclusion, this study provides a comprehensive analysis of gut microbiota shifts during diarrhea treatment in Chinese pangolins, indicating that probiotic agents could be an adjuvant therapy when treating diarrhea in captive pangolins.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108036"},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102697","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}

{"title":"Antimicrobial and antibiofilm effects of a leucine-substituted rice peptide against Porphyromonas gingivalis and Fusobacterium nucleatum","authors":"Yukari Aoki-Nonaka ,&nbsp;Aoi Matsugishi-Nasu ,&nbsp;Hnin Yu Lwin,&nbsp;Yukako Minato,&nbsp;Daiki Ando,&nbsp;Yuko Warita,&nbsp;Naoki Takahashi,&nbsp;Koichi Tabeta","doi":"10.1016/j.micpath.2025.108052","DOIUrl":"10.1016/j.micpath.2025.108052","url":null,"abstract":"<div><div>The aim of this study to elucidate the antibacterial and antibiofilm effects of a leucine-substituted peptide against periodontal pathogen. N3L peptide was designed as a leucine-substituted variant of the rice-derived AmyI-1-18 peptide. Subsequently, the minimum inhibitory concentration and minimum bactericidal concentration of N3L against <em>Porphyromonas gingivalis</em> and <em>Fusobacterium nucleatum</em> were determined. Furthermore, its membrane permeability was investigated by propidium iodide (PI) staining. Moreover, the effects of N3L on the gene expression of virulence factors were analyzed by reverse transcriptase quantitative polymerase chain reaction. The biofilm amount was assessed by crystal violet staining to analyze the biofilm control ability of N3L peptide. N3L demonstrated bactericidal activity against <em>P. gingivalis</em> and <em>F. nucleatum</em>, with notably enhanced antimicrobial activity against <em>P. gingivalis</em> compared with the parent peptide AmyI-1-18. PI staining indicated that N3L showed bacterial membrane permeability against <em>P. gingivalis</em> and <em>F. nucleatum</em>. Moreover, N3L significantly downregulated the expression levels of <em>fimA</em>, <em>rgpA</em>, <em>rgpB</em>, and <em>kgp</em> in <em>P. gingivalis</em> and <em>fadA</em> in <em>F. nucleatum</em>. This peptide also significantly inhibited biofilm formation and reduced established biofilms of <em>P. gingivalis</em> and <em>F. nucleatum</em>. The leucine-substituted rice peptide N3L, with its hydrophobicity and α-helix content higher than those of AmyI-1-18, showed enhanced antimicrobial and antibiofilm activities through membrane disruption and modulation of gene expressions related to adherence and metabolism. The leucine-substituted rice peptide N3L showed enhanced antimicrobial and antibiofilm activities against <em>P. gingivalis</em> and <em>F. nucleatum</em>.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108052"},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102716","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}

{"title":"pCramoll therapy decreases mortality and fungal burden in immunosuppressed mice infected with Cryptococcus gattii","authors":"Jannyson José Braz Jandú ,&nbsp;Marliete Carvalho Costa ,&nbsp;Elenildo Dário da Silva Júnior ,&nbsp;Fernanda Miguel de Andrade ,&nbsp;Marcia Vanusa da Silva ,&nbsp;Luana Cassandra Breitenbach Barroso Coelho ,&nbsp;Daniel Assis Santos ,&nbsp;Ronald Silva Jesus ,&nbsp;Karina Raquel Guilhon Machado ,&nbsp;Maria das Graças Carneiro da Cunha ,&nbsp;Luis Cláudio Nascimento Silva ,&nbsp;Maria Tereza dos Santos Correia","doi":"10.1016/j.micpath.2025.108043","DOIUrl":"10.1016/j.micpath.2025.108043","url":null,"abstract":"<div><div>Cryptococcosis is an infectious disease caused mainly by two species <em>Cryptococcus neoformans</em> and <em>C. gattii</em>, and presents a myriad of symptoms and courses with pulmonary and central nervous system (CNS) clinical manifestations. The infection occurs mainly in immunosuppressed individuals, but <em>C. gattii</em> infections has garnered attention due to its prevalence among seemingly healthy individuals. The main treatment consolidated is lipid formulation amphotericin B plus 5-flucytosine, used on moderate-to-severe pulmonary and disseminated infection, followed by fluconazole. Fluconazole is used for mild-to-moderate pulmonary infection, but resistance phenomena have improved the focus on the search for new antimicrobials and immunoregulatory agents. The purpose of this work is analyze the use of pCramoll, an immunomodulatory lectin obtained from seeds of <em>Cratylia mollis</em> Mart [an endemic plant of Caatinga (Northeastern Brazil semi-arid area)], as therapy against the cryptococcosis in infected mice under iatrogenic immunosuppression by 200 mg/kg cyclophosphamide and 150 mg/kg of 5-fluorouracil association. We observed that the immunosuppression promotes susceptibility to <em>C. gattii</em> infection (Graphical Abstract), resulting in a reduction of 21 days median of mice survival, and an increase in the lung fungal burden at the seventh- and forty-day post-infection. With 1 μg/animal/day pCramoll treatment, the immunosuppressed mice exhibited less fungal burden on the lungs and brain, and were observed to have an increase of 100 % in their survival rate (Graphical Abstract). This work shows for the first time the use of plant lectins as possible immunoregulatory tools in immunosuppressed animals infected with <em>C. gattii</em>.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108043"},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102753","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}

{"title":"Impact of gut microbiota dysbiosis on intestinal barrier integrity and systemic inflammation in a pre-eclampsia mouse model","authors":"Yefang Zhao ,&nbsp;Bingjie Wang ,&nbsp;Xujing Wei ,&nbsp;Dengxiang Liu ,&nbsp;Ruiping Wang ,&nbsp;Shasha Xie ,&nbsp;Zongxu Qiao ,&nbsp;Dan Cui ,&nbsp;Shaoke Hou ,&nbsp;Hongzhen Zhang","doi":"10.1016/j.micpath.2025.108053","DOIUrl":"10.1016/j.micpath.2025.108053","url":null,"abstract":"<div><div>Pre-eclampsia is characterized by systemic inflammation and endothelial dysfunction, with growing evidence suggesting a significant role for gut microbiota in its pathogenesis. This study investigated the effects of fecal microbiota transplantation from pre-eclamptic and healthy donors on intestinal barrier integrity and systemic inflammation in a mouse model. Fecal bacteria solutions from pre-eclamptic and healthy pregnant women were transplanted into pseudo-sterile mice. The expression of ZO-1 and Occludin in colon tissue was assessed using PCR, Western Blot, and immunohistochemistry. Urinary protein content, serum lipopolysaccharide (LPS), TNF-α, and IL-6 levels were measured by ELISA. Fecal microbiota transplantation from pre-eclamptic and healthy donors did not affect tissue morphology in mice but significantly compromised intestinal barrier integrity in the pre-eclampsia model group (PET). This was indicated by reduced levels of the tight junction proteins TJP1 and Occludin. The PET group also exhibited elevated urinary protein levels (4456.24 ± 1509.05 μg/ml) and increased serum levels of LPS (10.26 ± 3.91 μg/ml), TNF-α (13.34 ± 1.07 pg/ml), and IL-6 (16.48 ± 5.33 pg/ml), underscoring systemic inflammation associated with gut microbiota dysbiosis in pre-eclampsia. This study indicates that the dysregulation of the intestinal microbiota in patients with preeclampsia may disrupt the intestinal barrier function and exacerbate systemic inflammation. However, due to the limited number of donors and experimental conditions, the specific mechanism still requires further investigation.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108053"},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102756","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}

{"title":"Efficacy of bacteriophage cocktails administered through mucosal and non-mucosal routes for urinary tract infections caused by Enterobacter cloacae: A preclinical study","authors":"Srishti Singh ,&nbsp;Alok Kumar Singh ,&nbsp;Alakh Narayan Singh ,&nbsp;Sudhir Kumar Singh ,&nbsp;Virendra Bahadur Yadav ,&nbsp;Mayank Gangwar ,&nbsp;Minakshi Sahu ,&nbsp;Deepak Kumar ,&nbsp;Gopal Nath","doi":"10.1016/j.micpath.2025.108024","DOIUrl":"10.1016/j.micpath.2025.108024","url":null,"abstract":"<div><div>This preclinical study assessed the effectiveness of a phage cocktail in completely curing <em>Enterobacter cloacae</em>-associated urinary tract infections (UTIs) in a mouse model, employing various routes and dosages (both in quantity and frequency). Three lytic phages, designated ΦENT1, ΦENT2, and ΦENT3, were identified and characterised phenotypically using transmission electron microscopy (TEM) and genotypically through ERIC and restriction enzyme analysis. To induce a UTI, ten groups of female Swiss albino mice were inoculated with 100 μL containing 1 × 10⁹ CFU/mL via the urethral route with <em>E. cloacae</em> GNENT11213. The mice were subsequently treated with the phage cocktail via subcutaneous, oral, transurethral, and rectal routes. The efficacy of these routes was optimised at two doses of phages, namely 1 × 10⁹ PFU/mL (5 mice) and 1 × 10⁵ PFU/mL (5 mice). Furthermore, the levels of Endotoxins and Interleukin-6 (IL-6) were measured to assess the negative impact of phage therapy. Our findings indicated that <em>E. cloacae</em> GNENT11213 could be effectively eliminated with one dosage of 1 × 10⁹ Plaque-Forming Units per mouse (PFU/mouse) and two doses of the phage cocktail containing 1 × 10⁵ PFU/mouse administered through the urethra (local mucosa). Interestingly, higher concentrations of phage particles and multiple doses were necessary for other mucosal routes, such as oral and rectal administration, to effectively eradicate <em>E. cloacae</em> GNENT11213 at any stage of acute illness UTI. Furthermore, phage treatment did not significantly alter the levels of IL-6 and Endotoxins. Non-mucosal routes, such as subcutaneous, were ineffective in curing the infection.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108024"},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102710","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}