{"title":"Eugenol nanoparticle as a therapeutic agent against Pseudomonas infection in mice.","authors":"Sourav Ghosh, Tarakdas Basu","doi":"10.1093/femspd/ftaf014","DOIUrl":"10.1093/femspd/ftaf014","url":null,"abstract":"<p><p>We reported earlier about development of nano-formulation of an essential oil \"eugenol\" through its entrapment within animal protein \"gelatin,\" using a simple ultrasonication technique, followed by purification via ultracentrifugation. The synthesized eugenol nanoparticle (ENP) exhibited promising antibacterial and antibiofilm activity on pathogenic strain Pseudomonas aeruginosa MTCC 2488 in vitro. Here, we report on in vivo therapeutic efficacy of ENP against Pseudomonas-administered lung infection, developed in BALB/c mice. Our findings revealed that ENP treatment significantly reduced bacterial burden in infected lung tissues and promoted recovery from infection-associated weight loss, hypothermia, and fluid accumulation in mice. In addition, histopathological and immunological studies showed that the elevated level of inflammatory cytokines TNF-α, IL-1β, MCP-1, GM-CSF, and IFN-γ in lung tissue, serum, and broncho-alveolar lavage (BAL) fluid of Pseudomonas-infected mice were considerably attenuated to almost normal level by ENP treatment. Notably, free eugenol had not so high antipseudomonal action as ENP.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12741951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Akkermansia muciniphila attenuates sepsis-induced immunosuppression by shaping endotoxin-tolerant macrophage phenotypes.","authors":"Hang Qian, Fei Zhao","doi":"10.1093/femspd/ftaf013","DOIUrl":"10.1093/femspd/ftaf013","url":null,"abstract":"<p><p>Sepsis is a life-threatening condition characterized by immunosuppression, largely mediated by endotoxin tolerance. Akkermansia muciniphila (AKK), a gut probiotic, has been shown to modulate immune responses. In this study, 16S rRNA sequencing revealed decreased AKK levels in immunosuppressed individuals. In vitro experiments using RAW 264.7 macrophages demonstrated that endotoxin tolerance induced an M2 phenotype, which was reversed by AKK treatment, promoting an M1 phenotype. Additionally, AKK enhanced bacterial clearance of Pseudomonas aeruginosa. In vivo, AKK administration alleviated immunosuppression in an endotoxin-tolerant mouse model by modulating macrophage phenotypes. These findings highlight AKK as a potential therapeutic candidate for sepsis-induced immunosuppression.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12741952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression of Concern: Protective effects of Lactobacillus rhamnosus GG against human rotavirus-induced diarrhoea in a neonatal mouse model.","authors":"","doi":"10.1093/femspd/ftaf007","DOIUrl":"https://doi.org/10.1093/femspd/ftaf007","url":null,"abstract":"","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"83 ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer Kintner, Morgan Callaghan, Lillith Bulawa, Angela Chu, Zuchao Ma, David L Williams, Robert V Schoborg, Michael D Kruppa, Jennifer V Hall
{"title":"Dectin-1 stimulating β-glucans inhibit Chlamydia infections both in vitro and in vivo.","authors":"Jennifer Kintner, Morgan Callaghan, Lillith Bulawa, Angela Chu, Zuchao Ma, David L Williams, Robert V Schoborg, Michael D Kruppa, Jennifer V Hall","doi":"10.1093/femspd/ftaf002","DOIUrl":"10.1093/femspd/ftaf002","url":null,"abstract":"<p><p>Chlamydia trachomatis and Candida albicans are common inhabitants of the female genital tract. Candida albicans can impact the viability and pathogenesis of some bacteria. Previously, we investigated physical interactions between Ch. trachomatis elementary bodies (EBs) and Ca. albicans. This work indicated that EBs bind to Ca. albicans and become noninfectious by 24 h post-binding. Here, we continue our investigation of these interkingdom, polymicrobial interactions. Candida albicans adheres to bacteria or host surfaces via agglutinin-like sequence or heat shock 70 (Ssa) proteins. Chlamydia trachomatis EBs did not bind Ca. albicans Ssa2 deficient strains as efficiently as wild-type or complemented strains, indicating a role for this protein in chlamydial adherence to Candida. Additionally, Ca. albicans β-glucans inhibit chlamydial infection when exposure occurs during EB adsorption onto cervical cells. Laminarin, a β-glucan agonist of the C-type lectin receptor Dectin-1, inhibited chlamydial infection in both cervical epithelial cells and mice when exposure occurred prior to, during, or immediately following EB inoculation. Conversely, a Dectin-1 antagonist laminarin did not inhibit infection in vitro, suggesting that β-glucan inhibition of Ch. trachomatis requires C-type lectin receptor signaling. Overall, our data demonstrate that β-glucans from multiple species, including Ca. albicans, inhibit Chlamydia via stimulation of host-signaling pathways.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ashlesh K Murthy, Erika Wright-McAfee, Katerina Warda, Lindsay N Moy, Nhi Bui, Tarakarama Musunuri, S Manam, Clemence Z Chako, Kyle H Ramsey, Weidang Li
{"title":"Protective Anti-Chlamydial Vaccine Regimen-Induced CD4+ T cell Response Mediates Early Inhibition of Pathogenic CD8+ T cell Response Following Genital Challenge","authors":"Ashlesh K Murthy, Erika Wright-McAfee, Katerina Warda, Lindsay N Moy, Nhi Bui, Tarakarama Musunuri, S Manam, Clemence Z Chako, Kyle H Ramsey, Weidang Li","doi":"10.1093/femspd/ftae008","DOIUrl":"https://doi.org/10.1093/femspd/ftae008","url":null,"abstract":"We have demonstrated previously that TNF-α-producing CD8 + T cells mediate chlamydial pathogenesis, likely in an antigen (Ag)-specific fashion. Here we hypothesize that inhibition of Ag-specific CD8 + T cell response after immunization and/or challenge would correlate with protection against oviduct pathology induced by a protective vaccine regimen. Intranasal (i.n.) live chlamydial elementary body (EB), intramuscular (i.m.) live EB, or i.n. irrelevant antigen, bovine serum albumin (BSA), immunized animals induced near-total protection, 50% protection, or no protection, respectively against oviduct pathology following i.vag. C. muridarum challenge. In these models, we evaluated Ag-specific CD8 + T cell cytokine response at various time-periods after immunization or challenge. The results show protective efficacy of vaccine regimens correlated with reduction of Ag-specific CD8 + T cell TNF-α responses following i.vag. chlamydial challenge, not after immunization. Depletion of CD4 + T cells abrogated, whereas adoptive transfer of Ag-specific CD4 + T cells induced the significant reduction of Ag-specific CD8+ T cell TNF- α response after chlamydial challenge. In conclusion, protective anti-chlamydial vaccine regimens induce Ag-specific CD4 + T cell response that mediate early inhibition of pathogenic CD8 + T cell response following challenge and may serve as a predictive biomarker of protection against Chlamydia -induced chronic pathologies.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"24 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140841265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"From Fever to Action: Diagnosis, Treatment, and Prevention of Acute Undifferentiated Febrile Illnesses","authors":"Muttiah Barathan","doi":"10.1093/femspd/ftae006","DOIUrl":"https://doi.org/10.1093/femspd/ftae006","url":null,"abstract":"Acute Undifferentiated Febrile Illness (AUFI) presents a clinical challenge, often characterized by sudden fever, non-specific symptoms, and potential life-threatening implications. This review highlights the global prevalence, types, challenges, and implications of AUFI, especially in tropical and subtropical regions where infectious diseases thrive. It delves into the difficulties in diagnosis, prevalence rates, regional variations, and potential causes, ranging from bacterial and viral infections to zoonotic diseases. Furthermore, it explores treatment strategies, preventive measures, and the critical role of the One Health approach in addressing AUFI. The paper also addresses the emerging zoonotic risks and ongoing outbreaks, including COVID-19, Rickettsia spp., and other novel pathogens, emphasizing their impact on AUFI diagnosis and management. Challenges in resource-limited settings are analyzed, highlighting the need for bolstered healthcare infrastructure, enhanced diagnostics, and collaborative One Health strategies. Amidst the complexity of emerging zoonotic threats, this review underscores the urgency for a multifaceted approach to mitigate the growing burden of AUFI, ensuring early diagnosis, appropriate treatment, and effective prevention strategies.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"57 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140598553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shan Cheng, Yi Liu, Bei He, Jinrong Zhang, Yewei Yang, Xinglv Wang, Zhongyu Li
{"title":"Chlamydia trachomatis upregulates lncRNA CYTOR to mediate autophagy through miR-206/MAPK1 axis.","authors":"Shan Cheng, Yi Liu, Bei He, Jinrong Zhang, Yewei Yang, Xinglv Wang, Zhongyu Li","doi":"10.1093/femspd/ftae011","DOIUrl":"10.1093/femspd/ftae011","url":null,"abstract":"<p><p>Chlamydia trachomatis infection can be regulated by autophagy-related genes. LncRNA CYTOR has been proven to be involved in autophagy. In this research, we investigated the role of CYTOR in autophagy induced by C. trachomatis and the potential mechanisms. After C. trachomatis infection, CYTOR and MAPK1 were up-regulated and miR-206 was down-regulated, meanwhile, the autophagy-related protein Beclin1 and LC3-Ⅱ/LC3-Ⅰ ratio were increased. Interference with CYTOR or overexpression with miR-206 downregulated the autophagy-related protein Beclin1 and the number of autophagic spots LC3, decreased the protein ratio of LC3-II/LC3-I, and upregulated the expression of P62 protein. The luciferase reporter assay confirmed that CYTOR acted as a sponge for miR-206 to target MAPK1. In addition, CYTOR promoted autophagy induced by C. trachomatis infection through the MAPK1/ERK signaling pathway activation. Taken together, we have identified a novel molecular mechanism that the CYTOR/miR-206/MAPK1 axis was involved in the regulation of autophagy in C. trachomatis infection. This work provides an experimental basis for elucidating the pathogenesis of C. trachomatis for the treatment, prevention and control of related infectious diseases.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Raguib Munif, Robert A Hart, Rukshan A M Rafeek, Amali C Mallawaarachchi, Lyndal Anderson, David J McMillan, Kadaba S Sriprakash, Natkunam Ketheesan
{"title":"Mechanisms that potentially contribute to the development of post-streptococcal glomerulonephritis.","authors":"Mohammad Raguib Munif, Robert A Hart, Rukshan A M Rafeek, Amali C Mallawaarachchi, Lyndal Anderson, David J McMillan, Kadaba S Sriprakash, Natkunam Ketheesan","doi":"10.1093/femspd/ftae024","DOIUrl":"10.1093/femspd/ftae024","url":null,"abstract":"<p><p>Post-streptococcal glomerulonephritis (PSGN) is primarily associated with preceding group A streptococcal skin or throat infections, now mainly observed in economically disadvantaged communities. This condition significantly predisposes individuals to later-life chronic kidney disease and concurrent renal complications, with the elderly experiencing increased severity and less favourable outcomes. Streptococcal pyrogenic exotoxin B and nephritis-associated plasmin receptor are identified nephritogenic antigens (nephritogens). Pathogenesis of PSGN is multifactorial. It can involve the formation of antigen-antibody immune complexes, causing inflammatory damage to renal glomeruli. Deposition of circulating immune complexes or in situ formation of immune complexes in glomeruli, or both, results in glomerulonephritis. Additionally, molecular mimicry is hypothesized as a mechanism, wherein cross-reactivity between anti-streptococcal antibodies and glomerular intrinsic matrix proteins leads to glomerulonephritis. Besides, as observed in clinical studies, streptococcal inhibitor of complement, a streptococcal-secreted protein, can also be associated with PSGN. However, the interplay between these streptococcal antigens in the pathogenesis of PSGN necessitates further investigation. Despite the clinical significance of PSGN, the lack of credible animal models poses challenges in understanding the association between streptococcal antigens and the disease process. This review outlines the postulated mechanisms implicated in the development of PSGN with possible therapeutic approaches.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eva Vaňková, Jaroslav Julák, Anna Machková, Klára Obrová, Anja Klančnik, Sonja Smole Možina, Vladimír Scholtz
{"title":"Overcoming antibiotic resistance: non-thermal plasma and antibiotics combination inhibits important pathogens.","authors":"Eva Vaňková, Jaroslav Julák, Anna Machková, Klára Obrová, Anja Klančnik, Sonja Smole Možina, Vladimír Scholtz","doi":"10.1093/femspd/ftae007","DOIUrl":"10.1093/femspd/ftae007","url":null,"abstract":"<p><p>Antibiotic resistance (ATBR) is increasing every year as the overuse of antibiotics (ATBs) and the lack of newly emerging antimicrobial agents lead to an efficient pathogen escape from ATBs action. This trend is alarming and the World Health Organization warned in 2021 that ATBR could become the leading cause of death worldwide by 2050. The development of novel ATBs is not fast enough considering the situation, and alternative strategies are therefore urgently required. One such alternative may be the use of non-thermal plasma (NTP), a well-established antimicrobial agent actively used in a growing number of medical fields. Despite its efficiency, NTP alone is not always sufficient to completely eliminate pathogens. However, NTP combined with ATBs is more potent and evidence has been emerging over the last few years proving this is a robust and highly effective strategy to fight resistant pathogens. This minireview summarizes experimental research addressing the potential of the NTP-ATBs combination, particularly for inhibiting planktonic and biofilm growth and treating infections in mouse models caused by methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. The published studies highlight this combination as a promising solution to emerging ATBR, and further research is therefore highly desirable.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11094553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative analysis of genomic characteristics and immune response between Mycobacterium tuberculosis strains cultured continuously for 25 years and H37Rv.","authors":"Chuanzhi Zhu, Jing Dong, Yuheng Duan, Hongyan Jia, Lanyue Zhang, Aiying Xing, Boping Du, Qi Sun, Yinxia Huang, Zongde Zhang, Liping Pan, Zihui Li","doi":"10.1093/femspd/ftae014","DOIUrl":"10.1093/femspd/ftae014","url":null,"abstract":"<p><p>Tuberculosis (TB) continues to pose a significant global health challenge, emphasizing the critical need for effective preventive measures. Although many studies have tried to develop new attenuated vaccines, there is no effective TB vaccine. In this study, we report a novel attenuated Mycobacterium tuberculosis (M. tb) strain, CHVAC-25, cultured continuously for 25 years in the laboratory. CHVAC-25 exhibited significantly reduced virulence compared to both the virulent H37Rv strain in C57BL/6J and severe combined immunodeficiency disease mice. The comparative genomic analysis identified 93 potential absent genomic segments and 65 single nucleotide polymorphic sites across 47 coding genes. Notably, the deletion mutation of ppsC (Rv2933) involved in phthiocerol dimycocerosate synthesis likely contributes to CHVAC-25 virulence attenuation. Furthermore, the comparative analysis of immune responses between H37Rv- and CHVAC-25-infected macrophages showed that CHVAC-25 triggered a robust upregulation of 173 genes, particularly cytokines crucial for combating M. tb infection. Additionally, the survival of CHVAC-25 was significantly reduced compared to H37Rv in macrophages. These findings reiterate the possibility of obtaining attenuated M. tb strains through prolonged laboratory cultivation, echoing the initial conception of H37Ra nearly a century ago. Additionally, the similarity of CHVAC-25 to genotypes associated with attenuated M. tb vaccine positions it as a promising candidate for TB vaccine development.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}