Shotaro Abe, Jun Ohshima, Masayoshi Morita, Nobutake Tanaka, Mikako Hayashi
{"title":"Porphyromonas gingivalis Suppresses Interferon-Gamma Signaling in Macrophages Through a Contact-Dependent, Gingipain-Mediated Mechanism","authors":"Shotaro Abe, Jun Ohshima, Masayoshi Morita, Nobutake Tanaka, Mikako Hayashi","doi":"10.1002/mbo3.70290","DOIUrl":"10.1002/mbo3.70290","url":null,"abstract":"<p>Interferon signaling serves as a crucial defense mechanism for host cells against intracellular pathogens. Interferon-gamma (IFN-γ) binding to macrophages impacts the expression of approximately 2000 genes, activating them to enhance intracellular bactericidal activity. While various immune evasion strategies of <i>Porphyromonas gingivalis</i> have been extensively studied, the specific mechanisms by which it suppresses IFN-γ-mediated macrophage activation remain insufficiently characterized. In this study, we elucidated the molecular mechanism by which <i>P. gingivalis</i> suppresses interferon signaling in macrophages, with a particular focus on <i>STAT1</i> transcript abundance, because <i>STAT1</i> encodes a central transcription factor in the IFN-γ pathway. RNA-seq analysis revealed that <i>P. gingivalis</i> infection reduced the mRNA abundance of approximately 41% of genes upregulated following IFN-γ stimulation, including <i>STAT1</i> transcripts and other interferon-related genes. Further experiments showed that direct contact between the bacterium and host cells is necessary for this inhibition. This process involves the Type IX Secretion System (T9SS) and gingipains. Notably, strains lacking all gingipains (Kgp, RgpA, and RgpB) failed to suppress <i>STAT1</i> transcript abundance and instead allowed nuclear translocation of phosphorylated STAT1. These gingipain-deficient strains also exhibited reduced invasive ability, correlating with their diminished capacity to suppress interferon signaling and macrophage activation. In conclusion, our findings demonstrate that <i>P. gingivalis</i> inhibits interferon signaling in macrophages through intracellular infiltration, with T9SS and gingipains playing essential roles in this immunosuppressive mechanism. These results provide valuable insights into the immune evasion strategies of <i>P. gingivalis</i> and suggest potential therapeutic targets for combating periodontopathic diseases.</p>","PeriodicalId":18573,"journal":{"name":"MicrobiologyOpen","volume":"15 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mbo3.70290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenwen Yu, Shuqing Ma, Fen Xu, Xiangmin Han, Ming Li, Yuanqi Zhu, Sufei Pan, Sujun Hou, Chunqing Ma, Fawen Deng, Shifu Wang, the SPARSS net Working Group
{"title":"The Influence of COVID-19 on the Composition and Drug Resistance of Pleural Effusion in Shandong Province","authors":"Wenwen Yu, Shuqing Ma, Fen Xu, Xiangmin Han, Ming Li, Yuanqi Zhu, Sufei Pan, Sujun Hou, Chunqing Ma, Fawen Deng, Shifu Wang, the SPARSS net Working Group","doi":"10.1002/mbo3.70285","DOIUrl":"10.1002/mbo3.70285","url":null,"abstract":"<p>To analyze the composition and drug resistance changes of pleural effusion in Shandong region from 2017 to 2024, and to provide a basis for clinical empirical treatment and future public health strategies. Uese the WHONET5.6 software to analyze the data reported by the SPARSS network. A total of 6336 pathogens was isolated, 3876 were Gram-positive bacteria and 2211 were Gram-negative bacteria. The top five pathogens are <i>Staphylococcus aureus</i>, <i>Staphylococcus epidermidis</i>, <i>Klebsiella pneumoniae</i>, <i>Streptococcus constellatus</i>, and <i>Escherichia coli</i>. The main pathogens in male patients are <i>S. constellatus</i>, <i>S. epidermidis</i>, and <i>K. pneumoniae</i>, while in female patients, they are mainly <i>S. aureus</i>, <i>S. epidermidis</i>, and <i>E. coli</i>. The detection rate of <i>S. constellatus</i> rose from 4.3% to 8.1% after the COVID-19 pandemic (<i>p</i> < 0.0001); <i>K. pneumoniae</i> rose from 6.9% to 8.9%(<i>p</i> = 0.0264), and its resistance rate to meropenem increased from 2.1% to 18.3% (<i>p</i> = 0.0063). The detection rate of methicillin-resistant <i>Staphylococcus aureus</i> has remained largely unaffected by the COVID-19. The resistance rate of <i>Candida albicans</i> to fluconazole is as high as 12.5%. The pathogen spectrum of pleural effusion in Shandong Province is mainly Gram-positive bacteria. Coagulase-negative staphylococci were among the most common isolates, yet their role as true pathogens versus culture contaminants remains to be clarified in clinical practice. Moreover, after the epidemic, the carbapenem resistance of <i>K. pneumoniae</i> has significantly increased, and the problem of fungal drug resistance also needs to be paid attention to continuous monitoring to guide the rational use of drugs in clinical practice.</p>","PeriodicalId":18573,"journal":{"name":"MicrobiologyOpen","volume":"15 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mbo3.70285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahmad Fadhlullah Husaini, Margaretta Christita, Rizal Maarif Rukmana, Arida Susilowati, Keni Vidilaseris
{"title":"Reduction of Hexavalent Chromium by Stenotrophomonas and Bacillus","authors":"Ahmad Fadhlullah Husaini, Margaretta Christita, Rizal Maarif Rukmana, Arida Susilowati, Keni Vidilaseris","doi":"10.1002/mbo3.70286","DOIUrl":"10.1002/mbo3.70286","url":null,"abstract":"<p>Hexavalent chromium [Cr(VI)] is a widespread environmental pollutant, posing a significant health risk to ecosystems and humans. Bioremediation using microorganisms offers a cost-effective strategy for its detoxification. This review highlights recent advances in Cr(VI) reduction by <i>Stenotrophomonas</i> and <i>Bacillus</i> species, two bacterial genera with strong potential for chromium detoxification. <i>Stenotrophomonas</i> species primarily rely on intracellular enzymatic reduction mechanisms, often mediated by chromate reductases such as ChrR and heme proteins that link chromium detoxification with iron homeostasis. In contrast, <i>Bacillus</i> species employ a broader range of strategies, combining intracellular and extracellular enzymatic reduction, biosorption, and bioaccumulation, supported by stress-response and efflux systems that confer exceptional tolerance to Cr(VI). Comparative analysis reveals complementary metabolic strengths: <i>Stenotrophomonas</i> excels in rapid enzymatic detoxification, while <i>Bacillus</i> offers long-term stability through spore formation and surface-associated sequestration. Together, these traits underscore the promise of mixed consortia featuring both genera for scalable and resilient chromium bioremediation systems. Future research integrating omics-guided pathway mapping, microbial engineering, and biosafety control is expected to accelerate the deployment of efficient and safe Cr(VI) bioremediation technologies.</p>","PeriodicalId":18573,"journal":{"name":"MicrobiologyOpen","volume":"15 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parham Parnian, Paraskevi K. Zoga, Haydar A. S. Aljaafari, Hannah Chicchelly, Michael Toops, Eric Nuxoll
{"title":"Dispersion Inhibits Thermal Mitigation of Pseudomonas aeruginosa Biofilms on Self-Heating Surfaces","authors":"Parham Parnian, Paraskevi K. Zoga, Haydar A. S. Aljaafari, Hannah Chicchelly, Michael Toops, Eric Nuxoll","doi":"10.1002/mbo3.70283","DOIUrl":"10.1002/mbo3.70283","url":null,"abstract":"<p>Bacterial biofilms on medical implants are a major problem, typically requiring explantation and replacement of the biofilm-colonized implant. Thermal mitigation of these biofilms <i>in situ</i> has shown great promise in the laboratory, where the thermal shock can be most precisely delivered by immersion in hot media. Clinical implementation requires delivering the shock from the implant surface, however, leaving the surroundings at a cooler temperature. This study hypothesized that bacteria may rapidly, reversibly disperse into the cooler surroundings to partially evade the shock and tested this hypothesis by thermally shocking <i>Pseudomonas aeruginosa</i> biofilms on thermoelectric devices under media with different heat sink conditions. The time scale and equilibrium constant of this dispersion were investigated in ambient temperature immersion studies, and the effect of thermal shock on bacterial dispersion rate was investigated in a flow cell using biofilms grown on thermoelectric devices. The results showed that biofilms equilibrate with surrounding media in seconds, that a small fraction of bacteria in the biofilm are much less prone to dispersion, that thermal shock triggers an immediate increase in dispersion, and that shocking biofilms via their substrate in cooler surrounding decreases shock efficacy compared to shocks where the surrounding's temperature approaches that of the substrate.</p>","PeriodicalId":18573,"journal":{"name":"MicrobiologyOpen","volume":"15 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Meta-Analysis of COVID-19 Cluster Events Suggestive of Long-Distance Airborne Transmission/Inhalation","authors":"Mayuko Yagi, Ryoma Tasaki, Jun Komano","doi":"10.1002/mbo3.70232","DOIUrl":"10.1002/mbo3.70232","url":null,"abstract":"<p>SARS-CoV-2 spreads through both contact and airborne routes, the latter encompassing airborne transmission/inhalation as well as the direct deposition of infectious respiratory particles. During the early phase of the COVID-19 pandemic, numerous cluster events were suspected to involve long-distance airborne transmission/inhalation. We conducted a comparative analysis of these cluster events to characterize outbreak settings and associated clinical parameters. Thirteen cluster events from 2020 attributed to the original SARS-CoV-2 strain were examined, including choral activities, indoor sports, and bus tours. Incubation periods and infection–hospitalization rates (IHRs) were compared across settings and against estimates from large-scale cohort studies that predominantly reflect transmission via direct deposition. Statistical analyses were performed using the Mann–Whitney <i>U</i> test, Student's <i>t</i>-test, and Fisher's exact test (<i>p</i> < 0.05). The mean incubation period in suspected long-distance airborne transmission/inhalation cases was 6.1 ± 3.9 days (median: 5 days; <i>N</i> = 176), with indoor sports and choral events showing significantly shorter incubation periods (<i>p</i> = 0.034). The average IHR was 6.7 ± 12.5%, with significantly higher rates in choral clusters (<i>p</i> = 0.013). Age-adjusted IHRs were lower in long-distance airborne transmission/inhalation-related clusters than those reported from contact-tracing datasets. This analysis provides an integrated evaluation of long-distance airborne transmission/inhalation settings and their associated clinical characteristics. Activities involving vigorous respiration may contribute to shorter incubation periods and higher disease severity, potentially reflecting increased viral inoculum at exposure.</p>","PeriodicalId":18573,"journal":{"name":"MicrobiologyOpen","volume":"15 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tatjana Kazaka, Nikita Zrelovs, Inara Akopjana, Janis Bogans, Juris Jansons, Andris Dislers, Andris Kazaks
{"title":"Investigation of Recombinantly Produced Endolysins Reveals a Modular Enzyme Shared by Several Enterobacteria Phages to Exhibit Broad-Range Lytic Activity Against Different Orders of Gammaproteobacteria.","authors":"Tatjana Kazaka, Nikita Zrelovs, Inara Akopjana, Janis Bogans, Juris Jansons, Andris Dislers, Andris Kazaks","doi":"10.1002/mbo3.70293","DOIUrl":"10.1002/mbo3.70293","url":null,"abstract":"<p><p>Endolysins or murein hydrolases are hydrolytic enzymes produced by bacteriophages to cleave the host's cell wall during the final stage of the lytic cycle. Whereas globular endolysins are composed of a single enzymatically active domain (EAD), modular endolysins have at least two recognizable modules, often comprising a cell wall binding domain coupled to an EAD. Although such enzymes seem to be rarer, their activity often exceeds that of their globular counterparts. Here, we explored five previously uncharacterized modular endolysins for their expression, purification, and activity against a panel of distinct environmental Gram-negative bacteria. Out of the selected endolysins derived from Enterobacteria-infecting phages, two were soluble and were purified to near homogeneity. Among them, endolysin shared by several Enterobacteria phages, referred to as El1, exhibited a notable bacteriolytic activity not only from within, but also from without the cells. The effects of the studied enzyme on bacterial growth and viability were studied in detail in Escherichia coli. Visual inspection of the treated cells verified that the enzyme could penetrate the E. coli cell membrane when applied exogenously. Interestingly, El1 was active in the absence of ethylenediaminetetraacetic acid (EDTA) against multiple environmental Gram-negative bacteria representing different Gammaproteobacteria orders. Although the exact Gram-negative lysis mechanism of El1 remains unknown, the breadth of its target range suggests El1 as a promising candidate for future studies to scrutinize natural endolysin interactions differences against evolutionary distinct bacteria.</p>","PeriodicalId":18573,"journal":{"name":"MicrobiologyOpen","volume":"15 2","pages":"e70293"},"PeriodicalIF":4.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tianyu Luo, Mengyao Xue, Yi Du, Huiying Chen, Ying Sun, Haidong Sun
{"title":"The Mechanism of Gut Microbiota in Breast Cancer Based on the Bulk Transcriptome, Mendelian Randomization Analysis and Single Cell RNA Sequencing.","authors":"Tianyu Luo, Mengyao Xue, Yi Du, Huiying Chen, Ying Sun, Haidong Sun","doi":"10.1002/mbo3.70284","DOIUrl":"10.1002/mbo3.70284","url":null,"abstract":"<p><p>Breast cancer (BC) is the leading cause of cancer death in women. Bidirectional regulation between BC and gut microbiota (GM) is established, but GM's mechanistic role in BC pathogenesis remains unclear. Public BC/control samples and GM genome-wide association study data underwent Mendelian randomization to identify GM-BC associations and GMRGs. DEGs between BC and controls were analyzed. Candidate genes were derived from intersecting DEGs and GMRGs. Machine learning identified biomarkers, validated by expression analysis. GSEA, immune infiltration, drug screening with molecular docking, and scRNA-seq were performed. Intersecting 3455 DEGs with GMRGs yielded eight candidates; MCM6 and NR3C1 were validated as biomarkers, enriched in DNA replication pathways. Immune infiltration showed 13 differential immune cells, with macrophages notably influencing biomarkers. Etoposide exhibited strong binding to biomarkers via docking. scRNA-seq identified epithelial cells as key, with stage-dependent biomarker expression. This study redefines BC as a microbiome-regulated network, identifying the MCM6/NR3C1 biomarker pair for early diagnosis and microbiome-targeted interventions.</p>","PeriodicalId":18573,"journal":{"name":"MicrobiologyOpen","volume":"15 2","pages":"e70284"},"PeriodicalIF":4.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paul D Veith, Michael G Leeming, Yu Yen Chen, Eric C Reynolds
{"title":"Cargo Secreted by the Type IX Secretion System of Porphyromonas gingivalis Are Tethered to O-Lipopolysaccharides via a Pentasaccharide Linker.","authors":"Paul D Veith, Michael G Leeming, Yu Yen Chen, Eric C Reynolds","doi":"10.1002/mbo3.70296","DOIUrl":"10.1002/mbo3.70296","url":null,"abstract":"<p><p>The Gram-negative oral pathogen, Porphyromonas gingivalis, uses the Type IX Secretion System (T9SS) to secrete major virulence factors (cargo proteins) and anchor them to the cell surface via a novel linking sugar, 2-N-seryl, 3-N-acetylglucuronamide (SAGA), which is a component of a specific type of lipopolysaccharide, A-LPS. The reported structure of the polysaccharide component (A-PS) was a repeating phosphorylated mannan whereas the PS of conventional O-LPS (O-PS) is a repeating Gal-Glu-Rha-GalNAc unit. Here, we have performed extensive mass spectrometric analyses of cargo protein-linked LPS with and without proteinase K treatment to determine the structure of A-LPS. Limited acid hydrolysis of the PS backbone with trifluoromethanesulfonic acid enabled long PS fragments linked to cargo-derived peptides to be identified for the first time. Unexpectedly, rather than finding A-PS units, up to eleven O-PS repeating units were found linked to cargo via a novel pentasaccharide linker designated A-LS, composed of SAGA-Hex-dHex(C<sub>4</sub>H<sub>4</sub>O<sub>3</sub>)(Pent)-Hex. In addition, samples from a wzzP/porT double mutant that produced free truncated O-PS were specifically hydrolyzed to cleave lipid A prior to MS analysis. In these samples A-LS was found attached to a limited number of O-PS repeating units that in turn were associated with a putative core oligosaccharide that included the LPS-specific sugar, 3-deoxy-d-manno-octulosonic acid (Kdo). The proposed structure of A-LPS explains all 11 genes specific to A-LPS biosynthesis, and provides the first structural evidence that cargo proteins such as the gingipains are anchored to the cell surface via a complete LPS molecule.</p>","PeriodicalId":18573,"journal":{"name":"MicrobiologyOpen","volume":"15 2","pages":"e70296"},"PeriodicalIF":4.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marietta Wolf, Jennifer Metz, Annette Wittmer, Klaus Pelz, Kirstin Vach, Christiane von Ohle, Diana Wolff, Cornelia Frese, Fabian Cieplik, Ali Al-Ahmad
{"title":"Using Selective Agar Containing Ciprofloxacin and Tetracycline Reveals Resistant Oral Microbiota in Healthy and Periodontitis Patients.","authors":"Marietta Wolf, Jennifer Metz, Annette Wittmer, Klaus Pelz, Kirstin Vach, Christiane von Ohle, Diana Wolff, Cornelia Frese, Fabian Cieplik, Ali Al-Ahmad","doi":"10.1002/mbo3.70298","DOIUrl":"https://doi.org/10.1002/mbo3.70298","url":null,"abstract":"<p><p>The oral cavity may act as a reservoir for antibiotic resistance. This study aimed to directly isolate and identify phenotypically resistant bacteria from the oral biofilm of healthy individuals and patients with periodontitis, using tetracycline, and ciprofloxacin containing selective agar. Furthermore, resistance of selected bacteria towards ampicillin was also evaluated. Plaque samples were collected from 12 patients (six healthy, six with periodontitis). Bacteria were cultured on selective agar containg defined antibiotic concentration and non-selective media under aerobic and anaerobic conditions, identified by MALDI-TOF mass spectrometry and 16S rDNA sequencing. The selected bacteria were subsequently tested for susceptibility using disk diffusion, E-test, and β-lactamase assay. 495 strains representing 106 species were isolated, including 54 aerobes/facultative anaerobes and 52 obligate anaerobes. Antibiotic resistance was observed in all subjects: 15.2% of isolates were resistant to tetracycline, 32.9% to ciprofloxacin, and 0.6% to ampicillin, with no significant differences between healthy and periodontitis groups. Tetracycline resistance was most frequent in the Streptococcus mitis group and Eubacterium spp., while ciprofloxacin resistance was dominated by Actinomyces-Schaalia group. Concluding, prevalence of antibiotic-resistance was comparable between healthy and periodontitis patients. Resistance was most prevalent against ciprofloxacin and tetracycline, highlighting the oral cavity as a relevant reservoir for antibiotic resistance.</p>","PeriodicalId":18573,"journal":{"name":"MicrobiologyOpen","volume":"15 2","pages":"e70298"},"PeriodicalIF":4.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Serena Messali, Anna Bertelli, Marta Giovanetti, Leonardo Sclavi, Massimo Ciccozzi, Mark Slevin, Arnaldo Caruso, Francesca Caccuri
{"title":"Decoding HIV-1 Next Move Through Matrix Protein p17 Quasi-Species.","authors":"Serena Messali, Anna Bertelli, Marta Giovanetti, Leonardo Sclavi, Massimo Ciccozzi, Mark Slevin, Arnaldo Caruso, Francesca Caccuri","doi":"10.1002/mbo3.70280","DOIUrl":"10.1002/mbo3.70280","url":null,"abstract":"<p><p>Since the introduction of combined antiretroviral therapy, acquired immune deficiency syndrome (AIDS)-related lymphomas account for a growing proportion of deaths among people living with human immunodeficiency virus (PLWHIV). In addition to the immune deficiency caused by AIDS and other cofactors, it has been shown that circulating HIV-1 proteins play a critical role in lymphoma development. The HIV-1 matrix protein p17 (refp17) is released from infected cells and accumulates in lymph nodes of PLWHIV, even during effective pharmacological control of viral replication. Circulating refp17 deregulates the biological activity of different immune cells. Moreover, p17 variants (vp17s) characterized by peculiar amino acid insertions occurring in the C-terminal region of the protein, differently from the refp17, also induce B-cell growth and clonogenicity. Notably, vp17s were found at a significantly higher prevalence in PLWHIV with than without lymphoma. HIV-1 mutants expressing clonogenic vp17s are actively spreading, and their prevalence is globally increasing worldwide. RNA viruses exist as a population of quasi-species, transmitted from one host to another, which ultimately leads to viral evolution by generating new master sequences. Here, we developed a next-generation sequence approach to evaluate the frequency of vp17 quasi-species in PLWHIV upon time and demonstrated that the incidence of vp17s also increases at quasi-species levels. Additionally, we established a regression model capable of predicting the insertions with higher probability to be fixed, further highlighting the evolutionary relevance of the C-terminal region in the adaptation of p17 to the human host.</p>","PeriodicalId":18573,"journal":{"name":"MicrobiologyOpen","volume":"15 2","pages":"e70280"},"PeriodicalIF":4.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}