Frontiers in Cellular and Infection Microbiology最新文献

{"title":"Exploring the repertoire of rhomboid proteases in <i>Cryptosporidium parvum</i> parasite: phylogenesis, structural motifs, and cellular localization in sporozoite cells.","authors":"Ilaria Vanni, Elisabetta Pizzi, Lucia Bertuccini, Alessandra Ludovisi, Fabio Tosini","doi":"10.3389/fcimb.2026.1733450","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1733450","url":null,"abstract":"<p><p><i>Cryptosporidium parvum</i> is an apicomplexan parasite and an important pathogen of mammals and humans, which can be infected by zoonotic transmission or directly by human-to-human contact. This parasite attacks the small intestine, and the main symptom is a watery diarrhea that can be particularly severe in newborns and deadly in immunodeficient subjects. Rhomboids are ubiquitous proteases embedded in cell membranes that act by cleaving other membrane proteins in or near their transmembrane domains. Apicomplexan rhomboids play an important role in approaching and invading the host cell. This study analyzed the phylogenetic origin, the structural motifs, and the subcellular localization of <i>C. parvum</i> rhomboids. Altogether, <i>C. parvum</i> possesses three rhomboids, namely, CpRom1, CpRom2, and CpRom3. The similarity search in <i>Cryptosporidium</i> genus revealed that <i>C. parvum</i> and other \"intestinal\" species lack a PARL-like rhomboid whereas this type of mitochondrial rhomboid was present in \"gastric\" species like <i>Cryptosporidium muris</i> and <i>Cryptosporidium andersoni.</i> At the genome level, this was revealed by a precise excision of the PARL-like gene in intestinal species whereas the rest of chromosomal synteny was well conserved among the <i>Cryptosporidium</i> species. The analysis of the structural domains revealed that <i>C. parvum</i> rhomboids can be classified as mixed secretases, and the comparison with orthologs from <i>Toxoplasma gondii</i> and <i>Plasmodium falciparum</i> showed that <i>C. parvum</i> rhomboids can be distinguished in two separate clusters based on similarities at the level of the catalytic sites. The three rhomboids were expressed simultaneously in the invasive stage of sporozoite, but each of them had a different spatial distribution. Indeed, CpRom1 had a dual localization: this rhomboid was internal at the apical complex, and it was also accumulated at the posterior pole of the sporozoite. Otherwise, CpRom2 was prevalently contained in the apical complex, and a point of accumulation was on the surface of the apical end. Differently from CpRom1 and CpRom2, CpRom3 is distributed along the entire surface of sporozoites. Finally, we listed 10 membrane proteins as candidate substrates for the <i>C. parvum</i> rhomboids based on the similarities with some proven substrates of apicomplexan rhomboids and the copresence in subcellular structures with the three rhomboids.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1733450"},"PeriodicalIF":4.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionary diversification and immunoprofiling of cathepsin L toolkit in common carp.","authors":"Sagar Nayak, Jiří Kyslík, Jovana Majstorović, Tamás Dobai, Veronika Žánová, Hana Pecková, Tomáš Korytář, Pavla Bartošová-Sojková","doi":"10.3389/fcimb.2026.1805838","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1805838","url":null,"abstract":"<p><p>Cysteine cathepsins are central regulators of lysosomal proteolysis, immune and metabolic homeostasis, yet the evolutionary forces shaping their diversification in vertebrates remain incompletely understood. Teleost fishes, particularly polyploid lineages, provide a powerful system to examine how whole-genome duplication remodels protease repertoires and regulatory networks. Here, using the polyploid common carp model, we identify nine cathepsin L (<i>ctsl)</i> paralogs retained after ancestral and lineage-specific whole-genome duplications, and show that these duplicates have undergone spatially distributed expression divergence. Paralog expression is strongly partitioned across tissues and immune compartments: <i>ctsl.1A/B</i> are enriched at mucosal barriers, whereas <i>ctslaA/B</i> predominate in metabolic and systemic immune hubs and are the only <i>ctsl</i> transcripts detected in circulating blood and head kidney leukocytes. Structural modelling predicts variation in protease loop architecture and active-site cleft geometry, suggesting divergent substrate preferences and/or catalytic properties. During infection with <i>Sphaerospora molnari</i>, a myxozoan pathogen, inflammatory cytokine induction is accompanied by transient <i>ctsl</i> downregulation, followed by a cell- and time-dependent reprogramming of proteolytic profiles as disease progresses. Collectively, these findings reveal a transcriptional pattern of <i>ctsl</i> regulation uncoupled from cytokine expression dynamics, emerging from retained <i>ctsl</i> duplicates. Moreover, they demonstrate how polyploidization can generate tissue- and cell-specific regulation of lysosomal pathways that balance host defense and homeostasis.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1805838"},"PeriodicalIF":4.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual antibacterial action of ethyl ferulate as antibiofilm molecule and antibiotic synergist against <i>Escherichia coli</i>.","authors":"Zhijin Zhang, Yubin Bai, Jing Xu, Rongbin Hu, Zixuan Shang, Xiaojuan Wei, Weiwei Wang, Bing Li, Zhen Zhu, Jiyu Zhang","doi":"10.3389/fcimb.2026.1789180","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1789180","url":null,"abstract":"<p><strong>Introduction: </strong>The biofilm formed by <i>Escherichia coli</i> enhances its pathogenicity and antibiotic resistance, posing a serious threat to human and animal health.</p><p><strong>Methods: </strong>This study evaluated the anti-biofilm and synergistic antibacterial effects of ethyl ferulate (EF) on <i>E. coli</i> using crystal violet (CV) staining and Alamar Blue (AB) assay. The expression levels of biofilm-related genes were analyzed by qRT-PCR.</p><p><strong>Results: </strong>The results demonstrated that EF effectively inhibited the formation of <i>E. coli</i> biofilm and the production of exopolysaccharides (EPS), while enhancing bacterial motility without affecting bacterial growth and metabolic activity. qRT-PCR analysis revealed that EF treatment significantly downregulated the expression of curli-related gene csgD and c-di-GMP-related genes (<i>pdeR</i> and <i>dgcM</i>), while upregulating the expression of flagella-related genes (<i>fliC</i>, <i>fliM</i>, and <i>motB</i>). Notably, EF exhibited significant antimicrobial synergistic effects when combined with commercially available antibiotics (fosfomycin sodium, cefquinome, gentamicin, tetracycline, and azithromycin), markedly enhancing their antibacterial efficacy.</p><p><strong>Discussion: </strong>These findings demonstrate that EF possesses potent anti-biofilm activity and holds promise as an antibacterial synergist, offering a promising strategy for the treatment of <i>E. coli</i> infections.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1789180"},"PeriodicalIF":4.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential oil-based hydrogels for oral candidiasis: preliminary formulation development, antifungal efficacy, and computational analysis via Monte Carlo simulation.","authors":"Adeola Tawakalitu Kola-Mustapha, Favour Temidayo John, Ronke Hadiyat Bello, Oluwakorede Joshua Adedeji, Yusuf Oluwagbenga Ghazali, Fahd Adebola Khalid-Salako, George Oche Ambrose","doi":"10.3389/fcimb.2026.1774370","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1774370","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to evaluate the inhibitory activity of the essential oils (EOs) of <i>Syzygium aromaticum</i> (formerly <i>Eugenia caryophyllata</i>) (clove) and <i>Cymbopogon flexuosus</i> (lemongrass) on <i>Candida albicans</i> (individually, and in combination) and incorporate them into hydrogels for the management of oral candidiasis.</p><p><strong>Method: </strong>The antifungal activity of both essential oils singly and in combination was performed using macro and checkerboard dilution against a standard <i>C. albicans</i> (ATCC 10231) and 14 clinical isolates.</p><p><strong>Results and discussion: </strong>Both EOs exhibited MIC of 100 μL/mL and MFC of 100 to 200 μL/mL depending on isolate; and a ΣFIC value of 0.75 indicating an additive outcome among 71% of the isolates. The EOs were formulated in hydrogels, the efficacies of which were tested using agar well diffusion method. The prepared hydrogels containing 3% w/w EOs in the ratio of 2:1 exhibited the best antifungal activity with desirably physicochemical and stability properties. Monte Carlo simulations (n = 10,000) further quantified the antifungal efficacy, revealing significantly enhanced inhibition arising from a synergistic effect of both EOs in combination. These findings highlight the promise of natural compounds as antifungal agents targeting critical fungal biosynthetic pathways and provide a basis for formulating EOs in hydrogels, potentially for the management of oral candidiasis.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1774370"},"PeriodicalIF":4.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Avian influenza and coronaviruses in live animal and wet markets in Laos: prevalence and public health considerations.","authors":"Patrick Höller, Elin Asp, Julia Pärssinen, Vannaphone Phouthana, Nittakone Soulinthone, Soukangna Keopaseuth, Kaisone Chanda, Jiaxin Ling, Johanna F Lindahl, Mahmoud M Naguib","doi":"10.3389/fcimb.2026.1786183","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1786183","url":null,"abstract":"<p><strong>Background: </strong>Live animal and wet markets (LWM) serve as critical interfaces where humans closely interact with domestic and peri-domestic animals, facilitating the spillover of zoonotic pathogens. Previous outbreaks of avian influenza viruses (AIV) and coronaviruses (CoV) linked to these markets underscore their significant public health risks. Despite the high density of LWM and historical viral spillovers in Southeast Asia, studies on the prevalence of respiratory viruses in LWM in Laos remain limited.</p><p><strong>Methods: </strong>To address this gap, we conducted a study across 20 LWM in the capital region of Laos in 2023. A total of 266 oropharyngeal swab samples from live and slaughtered ducks and chickens, the environment, and the air, were collected and screened for AIV and CoV. Furthermore, a questionnaire assessed the knowledge and attitudes of vendors and shoppers regarding disease risks at LWM.</p><p><strong>Results: </strong>We found a higher prevalence of AIV in swabs from live ducks (72%) compared to chickens (18%), while CoV was more common in chickens (13%) than ducks (5%). Air samples showed a prevalence of 38% for AIV and 8% for CoV. Subtyping of AIV revealed the circulation of the high pathogenicity H5N1 strain which is genetically characterized as clade 2.3.2.1e.</p><p><strong>Conclusions: </strong>These findings highlight the significant public health risks associated with LWM in Laos and emphasize the need for continuous surveillance and control measures to mitigate the risk of future zoonotic outbreaks.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1786183"},"PeriodicalIF":4.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota and metabolome signatures in preterm infants with high versus low risk for neurodevelopmental impairment: a prospective, matched, longitudinal multi-omics study.","authors":"Yan-Ping Tian, Qing-Hong Li, Yi-Ming Li, Jia-Yuan Zhao, Xin-Xin Wei, Jin-Ying Wang, Yu-Lan Zhou, Shun-Bo Yang, Wei Li, Pi Guo, Ling-Xi Wang, Ting-Ting Dai, Su-Fen Hu, Zeng-Quan Zhong, Ying-Mei Xie, Zhi-Hai Lv","doi":"10.3389/fcimb.2026.1799859","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1799859","url":null,"abstract":"<p><p>Preterm birth is a leading global cause of neurodevelopmental impairment (NDI), yet early predictive biomarkers remain elusive. The gut microbiome, developing in parallel with the brain and communicating via the microbiota-gut-brain axis, holds potential as a source of such biomarkers. However, specific longitudinal multi-omics signatures predictive of NDI risk in preterm infants are poorly defined. We conducted a prospective, matched, longitudinal study of 60 preterm infants, classified at 3 months corrected age (CA) into high-risk (HR, n=30) or low-risk (LR, n=30) groups for NDI based on combined motor (TIMP) and neurological (GMs) assessments. Fecal samples from birth (meconium) and 3 months CA underwent shotgun metagenomic sequencing and untargeted metabolomics. Groups were rigorously matched for gestational age, birth weight, sex, and clinical exposures. While α- and β-diversity did not differ between groups, profound taxonomic and functional divergence emerged. At 3 months CA, the LR gut was enriched with <i>Akkermansia muciniphila</i>, whereas the HR gut was dominated by <i>Klebsiella variicola</i>. Functional metagenomics revealed a dysbiotic HR trajectory, enriching pathways for bacterial virulence, stress response, and-notably-multiple pathways annotated for human neurodegenerative diseases, contrasting with LR expansion of core biosynthesis. Metabolomics confirmed a dysfunctional HR state, showing impaired amino acid metabolism and aberrant neuroactive pathway enrichment. Critically, meconium features correlated with 3-month neurobehavioral scores, demonstrating ultra-early predictive potential. Integrated networks at 3 months directly linked <i>Akkermansia muciniphila</i> and co-varying glycerophospholipids to superior neurodevelopmental scores, forming a beneficial \"<i>Akkermansia</i>-lipid\" axis, while <i>Klebsiella variicola</i> and triterpenoids formed a dysbiotic hub. Our study defines a high-risk gut ecosystem trajectory in preterm infants, characterized by early commensal depletion, pathobiont expansion, and a functional shift towards inflammation and neuroinflammation. These signatures offer novel targets for early risk prediction and microbiome-targeted interventions.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1799859"},"PeriodicalIF":4.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional analysis of type VII secretion system links to host immune evasion mechanism in <i>Mycobacterium tuberculosis</i>.","authors":"Karthikeyan Sundaram, Sridhar Rathinam, Ramalingam Bethunaickan, Uma Devi Ranganathan, Venkataraman Prabhu, Madhavan Dhanapal","doi":"10.3389/fcimb.2026.1797994","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1797994","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis</i> causes tuberculosis, an infectious disease; this acid-fast bacillus has various functions that enable it to survive within the host. Importantly, the type VII secretion system plays a vital role in host immune evasion. However, the early secretory antigenic target secretion system (ESX) component is crucial for mycobacteria survival, plays a significant role in bypassing the host immune response, and is linked to the prognosis of the disease. The review aims to analyze the ESX-associated genes' functions in defence mechanisms against host immune response. There are five types of ESX, with the ESX-1 effectors consisting of the heterodimers <i>EsxA/</i>ESAT-6 and <i>EsxB</i>/CFP-10. The precise membranolytic role of <i>EsxA</i> remains unclear; however, mycobacterial mutants deficient in <i>EsxA</i> show reduced membrane lytic activity and lack the ability to perforate phagosomes. ESX-5 substrates, such as glycine-rich and repetitive <i>PE_PGRS</i> proteins, are associated with immune evasion and pathogenicity. ESX-5 releases a substantial amount of PE and PPE proteins, along with various other immune-modulating substrates. In addition, ESX-3 facilitates iron acquisition through mycobactin and regulates metal homeostasis. ESX 4 has been studied in two fast-growing mycobacterial species: <i>M. abscessus</i> and <i>M. smegmatis</i>. Notably, conjugal DNA transfer in the recipient strain of <i>M. smegmatis</i> requires ESX-4. Therefore, the type VII secretion system of ESX-associated genes plays a crucial role in bacterial survival and action against autophagosome-lysosome fusion. Thus, studying this system will explore the effects of specific antigenic structures and their relationships with autophagy and mycobacterial self-defense mechanisms.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1797994"},"PeriodicalIF":4.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From genes to clinical application: a circulating four-gene signature for early diagnosis model of refractory <i>Mycoplasma pneumoniae</i> pneumonia.","authors":"Qiuting Wu, Zhiwei Lu, Xuehui He, Heping Wang, Xiaoli Zhang, Xiangtao Wu, Weihong Lu, Qi Feng, Qiru Su, Xingliang Zhang","doi":"10.3389/fcimb.2026.1741058","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1741058","url":null,"abstract":"<p><strong>Objective: </strong>Refractory <i>Mycoplasma pneumoniae</i> pneumonia (RMPP) presents a major clinical challenge in children, largely due to the absence of reliable early diagnostic markers, which contributes to delayed intervention and an increased risk of severe complications. This study aimed to identify early diagnostic biomarkers based on peripheral blood mononuclear cell (PBMC) gene expression profiles and to develop and validate a model capable of distinguishing RMPP from general MPP (GMPP) and healthy controls (Normal).</p><p><strong>Methods: </strong>A total of 349 children (117 Normal, 123 GMPP, and 109 RMPP) were chronologically divided into a prospective training cohort (n=295) for model development and a prospective validation cohort (n=54) for external validation. Single-cell RNA sequencing (scRNA-seq) was performed on PBMCs from a discovery cohort (n=8) randomly selected from the training cohort. Differentially expressed genes that were specifically and significantly upregulated in RMPP groups were screened as candidate early diagnostic biomarkers. After primer validation, expressions of these candidate genes were subsequently measured using RT-qPCR in the entire study population. A multinomial logistic regression model with backward selection was developed on the training set, externally validated in the validation set, and its internal validation was further assessed via 1000 bootstrap resamples of the full dataset.</p><p><strong>Result: </strong>scRNA-seq identified eight specifically upregulated genes in the RMPP group. Subsequent RT-qPCR validation in the training cohort confirmed four genes-<i>IGHM</i>, <i>NEAT1</i>, <i>IL32</i>, and <i>ACTG1</i>-as early diagnostic biomarker capable of differentiating among the three groups. A combined four-gene three-category logistic regression model (Normal/GMPP/RMPP) demonstrated strong performance, with macro-average area under the curve values of 0.968 and 0.987 in the training and external validation, respectively. The final model, refit on the full dataset, attained an overall diagnostic accuracy of 88.8% for three-category classification, which was further confirmed by bootstrap resampling (macro-average AUC = 0.969).</p><p><strong>Conclusion: </strong>We established a robust PBMC-based four-gene signature diagnostic model that accurately discriminates among Normal, GMPP, and RMPP statuses at an early disease stage. This model provides a clinically accessible and precise tool to facilitate early intervention and improve patient management.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1741058"},"PeriodicalIF":4.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate immune recognition and microenvironmental reprogramming in HPV-induced cervical cancer: from pattern recognition receptor activation to immune tolerance disruption.","authors":"Shahid Ullah Khan, Mustafa H Halawi, Mazen Almehmadi, Ramadan Taha, Ahmed Ezzat Ahmed, Mohammad Y Alfaifi, Ali A Shati, Serag Eldin I Elbehairi, Saleem Ahmad, Yasmene F Alanazi, Mohammed Al-Rasheed, Nuruliarizki Shinta Pandupuspitasari, Endang Widiastuti, Munir Ullah Khan","doi":"10.3389/fcimb.2026.1758873","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1758873","url":null,"abstract":"<p><p>Innate immune recognition plays a central role in determining the outcome of human papillomavirus (HPV) infection and the subsequent development of cervical cancer. This mini-review highlights how the reproductive tract's innate immune system, particularly Pattern Recognition Receptors (PRRs) such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs), detects HPV-associated molecular patterns and initiates antiviral defenses. HPV has evolved sophisticated strategies to evade these responses by suppressing PRR signaling, altering cytokine networks, reprogramming cellular metabolism, and reshaping the cervical microenvironment. These viral mechanisms contribute to the formation of a persistent post-infection microenvironment (PIM), characterized by impaired antigen presentation, regulatory immune cell infiltration, chronic inflammation, and metabolic and stromal remodeling, which collectively promote immune tolerance and carcinogenesis. Emerging evidence also highlights the roles of inflammasomes, type I interferon pathways, and extracellular vesicles in modulating innate immune responses during HPV infection. Understanding how innate immunity senses HPV and how the virus circumvents these pathways provides crucial insight into cervical cancer progression and offers opportunities for developing more effective immunotherapies, vaccines, and prevention strategies. This review synthesizes current advances in HPV-driven innate immune dysregulation within the reproductive tract and their implications for reproductive immunology and infection-associated malignancy.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1758873"},"PeriodicalIF":4.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of a carbapenem-resistant <i>Klebsiella pneumoniae</i> ST15-KL19 clone with elevated virulence potential in a tertiary hospital in China.","authors":"Guiling Li, Yujing Zhang, Guqi Ren, Longlong Tian, Xinan Jiao, Lin Sun, Chuanli Ren","doi":"10.3389/fcimb.2026.1745492","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1745492","url":null,"abstract":"<p><strong>Introduction: </strong>Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) has become a significant global health concern. The convergence of carbapenem resistance and elevated virulence potential has led to increasingly difficult-to-treat <i>K. pneumoniae</i> strains. Among these, ST15 is an expanding global high-risk clone, yet variants with elevated virulence potential carrying the KL19 capsular type remain rarely reported.</p><p><strong>Methods: </strong>In this study, we characterized the phenotypic and genomic features of a carbapenem-resistant <i>K. pneumoniae</i> ST15-KL19 clone exhibiting elevated virulence potential, isolated from a tertiary hospital in eastern China.</p><p><strong>Results: </strong>All isolates exhibited extensive drug resistance, including resistance to carbapenems, and carried the <i>bla</i> _KPC-2 gene. Whole-genome sequencing revealed a conserved chromosomal virulence-associated profile and hybrid plasmids carrying multiple resistance determinants. The <i>bla</i> _KPC-2 gene was located within a stable composite transposon, suggesting efficient mobility and long-term maintenance. Phylogenetic analysis demonstrated that the isolates were closely related to other Chinese ST15-KL19 strains, indicating recent clonal expansion and local dissemination.</p><p><strong>Discussion: </strong>The identification of this clone highlights the ongoing convergence of multidrug resistance and elevated virulence potential in <i>K. pneumoniae</i>, which poses challenges for infection control and clinical management. These findings emphasize the importance of continuous genomic surveillance to monitor the spread of high-risk <i>K. pneumoniae</i> lineages.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1745492"},"PeriodicalIF":4.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}