Infection and Immunity最新文献

筛选
英文 中文
Acquisition of daptomycin resistance in patients results in decreased virulence in Drosophila. 患者获得达托霉素耐药性导致果蝇毒力下降。
IF 2.9 3区 医学
Infection and Immunity Pub Date : 2025-06-10 Epub Date: 2025-05-23 DOI: 10.1128/iai.00594-24
Brigitte Lamy, Frédéric Laurent, Carolina J Simoes Da Silva, Ashima Wadhawan, Elizabeth V K Ledger, Camille Kolenda, Patricia Martins Simoes, Andrew M Edwards, Marc S Dionne
{"title":"Acquisition of daptomycin resistance in patients results in decreased virulence in <i>Drosophila</i>.","authors":"Brigitte Lamy, Frédéric Laurent, Carolina J Simoes Da Silva, Ashima Wadhawan, Elizabeth V K Ledger, Camille Kolenda, Patricia Martins Simoes, Andrew M Edwards, Marc S Dionne","doi":"10.1128/iai.00594-24","DOIUrl":"10.1128/iai.00594-24","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> can acquire antimicrobial resistance, which in turn may affect its pathogenic potential. Using a panel of paired clinical isolates collected before and after daptomycin resistance acquisition, most frequently through a single <i>mprF</i> mutation, we show a relationship between increasing daptomycin minimum inhibitory concentration and reduced virulence in a <i>Drosophila</i> systemic infection model. Analyzing toxin production, <i>in vitro</i> bacterial growth characteristics, and cell surface properties, we failed to link daptomycin resistance-related attenuated virulence to either reduced virulence factor production, reduced fitness, or any of the cell surface characteristics investigated. Competition assays in <i>Drosophila</i> also did not support any altered ability in immune evasion. Instead, using a panel of mutant flies defective for various immune components, we show that this daptomycin resistance-related attenuated virulence is mostly explained by greater susceptibility to the activity of <i>Drosophila</i> prophenoloxidase, a tyrosinase involved in melanization, but not to antimicrobial peptides or Bomanin antimicrobial effectors. Further investigation could not link daptomycin resistance-related attenuation of virulence to differential susceptibility to reactive oxygen species or quinones prominently associated with phenoloxidase bacterial-killing activity. Taken together, it appears that daptomycin resistance attenuates <i>Staphylococcus aureus</i> virulence through enhanced sensitivity to phenoloxidase based on a complex mechanism. Our study provides new insights into the understanding of the crosstalk between antimicrobial resistance, escape from immune killing, and virulence.IMPORTANCEThis study advances current knowledge in the field of host-microbe interactions and antimicrobial resistance by exploring crosstalk between antimicrobial resistance and virulence. It shows how acquiring antimicrobial resistance can alter bacterial virulence and helps shape virulence. Relative to the parental staphylococcal strain, daptomycin-resistant clinical isolates most often varied by one single mutation in a gene involved in the composition of the bacterial membrane, and these strains were much less virulent when fruit flies were infected. The difference in virulence is unrelated to changes in bacterial toxin production, bacterial growth, immune evasion, or cell surface properties. Instead, resistant strains were more vulnerable to a host proenzyme involved in the antibacterial melanization response, an important response deployed throughout the arthropods. We predict that daptomycin resistance forces staphylococci to alter the composition of their cell surface, which causes the bacteria to become more vulnerable to killing by melanization.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0059424"},"PeriodicalIF":2.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Maternal transfer of oral vaccine induced anti-OspA antibodies protects Peromyscus spp. from tick-transmitted Borrelia burgdorferi. 口服疫苗诱导的抗ospa抗体的母体转移保护Peromyscus sps免受蜱传播的伯氏疏螺旋体。
IF 2.9 3区 医学
Infection and Immunity Pub Date : 2025-06-10 Epub Date: 2025-05-19 DOI: 10.1128/iai.00216-25
Jose F Azevedo, Greg Joyner, Suman Kundu, Kamalika Samanta, Maria Gomes-Solecki
{"title":"Maternal transfer of oral vaccine induced anti-OspA antibodies protects <i>Peromyscus</i> spp. from tick-transmitted <i>Borrelia burgdorferi</i>.","authors":"Jose F Azevedo, Greg Joyner, Suman Kundu, Kamalika Samanta, Maria Gomes-Solecki","doi":"10.1128/iai.00216-25","DOIUrl":"10.1128/iai.00216-25","url":null,"abstract":"<p><p>The efficacy and duration of passive immunity protection depend on maternal antibody levels and transfer efficiency. We investigated whether oral vaccination of <i>Peromyscus leucopus</i> dams with recombinant outer surface protein A (OspA)-expressing <i>Escherichia coli</i> could induce maternal transfer of anti-OspA antibodies and protect pups from <i>Borrelia burgdorferi</i> challenge. Dams were vaccinated until breeding pairs were created (i), until parturition (ii), and until pups were 2 weeks old (iii). Pups were challenged with nymphal <i>Ixodes scapularis</i>-transmitted <i>B. burgdorferi</i> at ~4 weeks of age. Anti-OspA IgG was quantified in dams and pups, and anti<i>-B</i>. <i>burgdorferi</i> IgG was quantified in pups. <i>B. burgdorferi</i> burden was assessed by <i>flaB</i> quantitative PCR in pups' tissues ~4 weeks after tick challenge, and viability of <i>B. burgdorferi</i> was assessed by culture of the heart tissue. <i>P. leucopus</i> pups born to dams vaccinated until breeding had low serologic anti-OspA antibody and were not protected from tick-transmitted <i>B. burgdorferi</i> infection. However, when dams' vaccination extended until parturition and until pups were 2 weeks old, significant anti-OspA antibody transfer and protection from <i>B. burgdorferi</i> infection occurred. This was evidenced by the absence of antibody to <i>B. burgdorferi</i> PepVF, absence of <i>B. burgdorferi flaB</i> DNA in heart and bladder tissues, and absence of <i>flaB</i> in culture from heart tissues from pups euthanized >9 weeks after birth. We show that the transfer of anti-OspA antibodies from vaccinated <i>P. leucopus</i> dams to offspring prevents tick transmission and infection dynamics of <i>B. burgdorferi</i> in the major reservoir host of this spirochete in the USA.IMPORTANCEThis study contributes to our understanding of how interventions based in reservoir-targeted outer surface protein A vaccines designed to block transmission of <i>B. burgdorferi</i> from infected <i>Ixodes scapularis</i> ticks may disrupt the enzootic cycle of this spirochete and reduce incidence of Lyme disease.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0021625"},"PeriodicalIF":2.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
STING contributes to the inflammation and proliferation of Staphylococcus aureus via mitochondrial reactive oxygen species-hypoxic inducible factor 1α axis in epithelial cells. STING通过上皮细胞线粒体活性氧-缺氧诱导因子1α轴参与金黄色葡萄球菌的炎症和增殖。
IF 2.9 3区 医学
Infection and Immunity Pub Date : 2025-06-10 Epub Date: 2025-05-19 DOI: 10.1128/iai.00138-25
Xing Gao, Binfeng Wu, Yawei Qiu, Shiyuan Feng, Jinqiu Zhang, Jinfeng Miao
{"title":"STING contributes to the inflammation and proliferation of <i>Staphylococcus aureus</i> via mitochondrial reactive oxygen species-hypoxic inducible factor 1α axis in epithelial cells.","authors":"Xing Gao, Binfeng Wu, Yawei Qiu, Shiyuan Feng, Jinqiu Zhang, Jinfeng Miao","doi":"10.1128/iai.00138-25","DOIUrl":"10.1128/iai.00138-25","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> infection poses a serious threat to the dairy industry and public health safety. The stimulator of interferon gene (STING) signaling pathway has been well established as effective in defending against viral infections. However, the role of STING is controversial during bacterial infections. Herein, we provide an insight into the role of STING during <i>S. aureus</i> infection. Our data revealed that the STING signaling pathway was activated in <i>S. aureus</i>-infected cells. <i>In vitro</i> investigations demonstrated that inhibiting STING reduced inflammation, hypoxia-inducible factor-1 alpha (HIF1α) expression, and mitochondrial reactive oxygen species (mROS) production. Interestingly, blocking HIF1α eliminated the escalation of inflammation associated with STING. Additionally, suppressing mROS production significantly reduced HIF1α expression and inflammation levels, while elevating mROS had the opposite effect. These results indicate that STING promoted inflammation through the mROS-HIF1α pathway. Given that glycolysis is driven by HIF1α, we investigated the role of glycolysis during infection. As expected, STING-elevated inflammation was linked with HIF1α-driven glycolysis. In terms of pathogenesis, STING contributed to <i>S. aureus</i> proliferation within cells and mouse mammary glands. Collectively, our findings demonstrate that STING facilitates infection via the mROS-HIF1α-glycolysis axis, highlighting its potential as a promising anti-inflammatory target.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0013825"},"PeriodicalIF":2.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The unique histidine kinase, AtcS, regulates motility and pathogenicity of the periodontal pathobiont, Treponema denticola. 独特的组氨酸激酶,AtcS,调节牙周病原体密螺旋体的运动和致病性。
IF 2.9 3区 医学
Infection and Immunity Pub Date : 2025-05-13 Epub Date: 2025-04-02 DOI: 10.1128/iai.00112-25
Doaa N Abdallah, Annie N Hinson, Aidan D Moylan, Dhara T Patel, Bin Zhu, Richard T Marconi, Daniel P Miller
{"title":"The unique histidine kinase, AtcS, regulates motility and pathogenicity of the periodontal pathobiont, <i>Treponema denticola</i>.","authors":"Doaa N Abdallah, Annie N Hinson, Aidan D Moylan, Dhara T Patel, Bin Zhu, Richard T Marconi, Daniel P Miller","doi":"10.1128/iai.00112-25","DOIUrl":"10.1128/iai.00112-25","url":null,"abstract":"<p><p><i>Treponema denticola</i> is an obligate colonizer of the human gingival crevice and, along with other pathobionts, is highly associated with the development of periodontal disease. As periodontal disease develops, significant environmental changes occur in the subgingival crevice and oral microbiome. The ability to sense and respond to changing environmental conditions is essential to the ability of <i>T. denticola</i> to thrive and cause disease. Yet, our understanding of <i>T. denticola</i> sensory transduction and gene regulatory mechanisms is nearly absent. The AtcSR two-component system has been predicted to regulate several cellular processes, but its role in <i>T. denticola</i> adaptive responses has not been investigated. To address this knowledge gap, we constructed a deletion of the <i>atcS</i> gene, encoding the histidine kinase. We performed RNA sequencing, demonstrating that the deletion of <i>atcS</i> results in significant changes in the transcriptome of <i>T. denticola</i>. Most notably, the transcription of genes encoding proteins involved in motility and the dentilisin protease complex was reduced. Consistent with this, the deletion mutant displayed reduced dentilisin activity and motility. These phenotypes are critical to interactions with host cells and the pathogenicity of <i>T. denticola</i>. This aligns with our observation that the <i>atcS</i>-deficient strain had attenuated attachment and invasion of gingival epithelial cells and failed to induce alveolar bone loss in a murine periodontitis model, processes that are central to <i>T. denticola</i> virulence. This study is a significant step toward defining the role of the AtcSR two-component system in <i>T. denticola</i> pathogenicity.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0011225"},"PeriodicalIF":2.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Activation of macrophages by extracellular vesicles derived from Babesia-infected red blood cells. 由巴贝虫感染的红细胞衍生的细胞外囊泡激活巨噬细胞。
IF 2.9 3区 医学
Infection and Immunity Pub Date : 2025-05-13 Epub Date: 2025-04-02 DOI: 10.1128/iai.00333-24
Biniam Hagos, Ioana Brasov, Heather Branscome, Sujatha Rashid, Rebecca Bradford, Joseph Leonelli, Fatah Kashanchi, Choukri Ben Mamoun, Robert E Molestina
{"title":"Activation of macrophages by extracellular vesicles derived from <i>Babesia</i>-infected red blood cells.","authors":"Biniam Hagos, Ioana Brasov, Heather Branscome, Sujatha Rashid, Rebecca Bradford, Joseph Leonelli, Fatah Kashanchi, Choukri Ben Mamoun, Robert E Molestina","doi":"10.1128/iai.00333-24","DOIUrl":"10.1128/iai.00333-24","url":null,"abstract":"<p><p><i>Babesia microti</i> is the primary cause of human babesiosis in North America. Despite the emergence of the disease in recent years, the pathogenesis and immune response to <i>B. microti</i> infection remain poorly understood. Studies in laboratory mice have shown a critical role for macrophages in the elimination of parasites and infected red blood cells (iRBCs). Importantly, the underlying mechanisms that activate macrophages are still unknown. Recent evidence identified the release of extracellular vesicles (EVs) from <i>Babesia</i> iRBCs. EVs are spherical particles released from cell membranes under natural or pathological conditions that have been suggested to play roles in host-pathogen interactions among diseases caused by protozoan parasites. The present study examined whether EVs released from cultured <i>Babesia</i> iRBCs could activate macrophages and alter cytokine secretion. An analysis of vesicle size in EV fractions from <i>Babesia</i> iRBCs showed diverse populations in the <100 nm size range compared to EVs from uninfected RBCs. In co-culture experiments, EVs released by <i>B. microti</i> iRBCs appeared to be associated with macrophage membranes and cytoplasm, indicating uptake of these vesicles <i>in vitro</i>. Interestingly, the incubation of macrophages with EVs isolated from <i>Babesia</i> iRBC culture supernatants resulted in the activation of NF-κB and modulation of pro-inflammatory cytokines. These results support a role for <i>Babesia</i>-derived EVs in macrophage activation and provide new insights into the mechanisms involved in the induction of the innate immune response during babesiosis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0033324"},"PeriodicalIF":2.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Species-specific components of the Helicobacter pylori Cag type IV secretion system. 幽门螺杆菌Cag IV型分泌系统的物种特异性成分。
IF 2.9 3区 医学
Infection and Immunity Pub Date : 2025-05-13 Epub Date: 2025-04-10 DOI: 10.1128/iai.00493-24
Kaeli N Bryant, Arwen E Frick-Cheng, Lauren E Solecki, Heather K Kroh, W Hayes McDonald, D Borden Lacy, Mark S McClain, Melanie D Ohi, Timothy L Cover
{"title":"Species-specific components of the <i>Helicobacter pylori</i> Cag type IV secretion system.","authors":"Kaeli N Bryant, Arwen E Frick-Cheng, Lauren E Solecki, Heather K Kroh, W Hayes McDonald, D Borden Lacy, Mark S McClain, Melanie D Ohi, Timothy L Cover","doi":"10.1128/iai.00493-24","DOIUrl":"10.1128/iai.00493-24","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> strains containing the <i>cag</i> pathogenicity island (PAI) deliver an effector protein (CagA) and non-protein substrates into gastric cells through a process that requires the Cag type IV secretion system (T4SS). The Cag T4SS outer membrane core complex (OMCC) contains multiple copies of five proteins, two of which are species-specific proteins. By using modifications of a previously described OMCC immunopurification method and optimized mass spectrometric methods, we have now isolated additional <i>cag</i> PAI-encoded proteins that are present in lower relative abundance. Four of these proteins (CagW, CagL, CagI, and CagH) do not exhibit sequence relatedness to T4SS components in other bacterial species. Size exclusion chromatography analysis of immunopurified samples revealed that CagW, CagL, CagI, and CagH co-elute with OMCC components. These four Cag proteins are copurified with the OMCC in immunopurifications from a Δ<i>cag3</i> mutant strain (lacking peripheral OMCC components), but not from a Δ<i>cagX</i> mutant strain (defective in OMCC assembly). Negative stain electron microscopy analysis indicated that OMCC preparations isolated from Δ<i>cagW, cagL::kan,</i> Δ<i>cagI, and</i> Δ<i>cagH</i> mutant strains are indistinguishable from wild-type OMCCs. In summary, by using several complementary methods, we have identified multiple species-specific Cag proteins that are associated with the Cag T4SS OMCC and are required for T4SS activity.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"93 5","pages":"e0049324"},"PeriodicalIF":2.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The protein degradation system encoded by hslUV (ClpYQ) is dispensable for the virulence of Haemophilus ducreyi in human volunteers. 由hslv (ClpYQ)编码的蛋白质降解系统对于杜氏嗜血杆菌在人类志愿者中的毒力是必不可少的。
IF 2.8 3区 医学
Infection and Immunity Pub Date : 2025-05-13 Epub Date: 2025-04-10 DOI: 10.1128/iai.00577-24
Kate R Fortney, Julie A Brothwell, Teresa A Batteiger, Rory Duplantier, Barry P Katz, Stanley M Spinola
{"title":"The protein degradation system encoded by <i>hslUV</i> (<i>ClpYQ</i>) is dispensable for the virulence of <i>Haemophilus ducreyi</i> in human volunteers.","authors":"Kate R Fortney, Julie A Brothwell, Teresa A Batteiger, Rory Duplantier, Barry P Katz, Stanley M Spinola","doi":"10.1128/iai.00577-24","DOIUrl":"10.1128/iai.00577-24","url":null,"abstract":"<p><p><i>Haemophilus ducreyi</i> causes cutaneous ulcers in children who live in yaws-endemic countries and the genital ulcer disease chancroid. In the human host, <i>H. ducreyi</i> resides in an abscess and may need to resist both heat and oxidative stress, which result in aggregation and misfolding of bacterial proteins. In <i>Escherichia coli</i>, the <i>hslUV</i> (<i>clpYQ</i>) operon encodes a proteasome-like complex that degrades misfolded proteins and is upregulated during heat shock. In previous studies, we showed that <i>hslUV</i> transcripts are upregulated in experimental lesions caused by <i>H. ducreyi</i> in human volunteers, suggesting that HslUV may help <i>H. ducreyi</i> adapt to the abscess environment. Here, we constructed an unmarked <i>hslUV</i> operon deletion mutant, 35000HPΔ<i>hslUV</i>, in <i>H. ducreyi</i>. Whole-genome sequencing showed that compared to its parent (35000HP), the mutant contained only the deletion of interest. Six volunteers were inoculated at three sites on skin overlying the deltoid on opposite arms with 35000HP and 35000HPΔ<i>hslUV</i>. Within 24 h, papules formed at 88.9% (95% CI [69%, 100%]) at both parent and mutant-inoculated sites (<i>P</i> = 1.0). Pustules formed at 44.4% (95% CI [25.6%, 64.3%]) at parent-inoculated sites and 33.3% (95% CI [2.5%, 64.1%]) at mutant-inoculated sites (<i>P</i> = 0.17). Thus, the proteosome-like complex encoded by <i>hslUV</i> was dispensable for <i>H. ducreyi</i> virulence in humans. In the absence of <i>hslUV</i>, <i>H. ducreyi</i> likely utilizes other systems such as the Lon protease, ClpXP, and ClpB/DnaK to combat protein aggregation and misfolding, underscoring the importance of the functional redundancy of such systems in gram-negative pathogens.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"93 5","pages":"e0057724"},"PeriodicalIF":2.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cranberry constituents prevent SOS-mediated filamentation of uropathogenic Escherichia coli. 蔓越莓成分阻止尿路致病性大肠杆菌的sos介导的丝状变。
IF 2.9 3区 医学
Infection and Immunity Pub Date : 2025-05-13 Epub Date: 2025-04-10 DOI: 10.1128/iai.00600-24
Tracy Prinster, Alistair Harrison, Christopher Dick, Dennis J Horvath, Birong Li, Grace Sievers, Revanth Madamsetty, Jingwen Zhang, Kevin M Mason, Christina Khoo, Sheryl S Justice
{"title":"Cranberry constituents prevent SOS-mediated filamentation of uropathogenic <i>Escherichia coli</i>.","authors":"Tracy Prinster, Alistair Harrison, Christopher Dick, Dennis J Horvath, Birong Li, Grace Sievers, Revanth Madamsetty, Jingwen Zhang, Kevin M Mason, Christina Khoo, Sheryl S Justice","doi":"10.1128/iai.00600-24","DOIUrl":"10.1128/iai.00600-24","url":null,"abstract":"<p><p>The diameter, length, and shape of bacteria are maintained with such high fidelity that these parameters are classically used as metrics in the distinction of bacterial species. Increasing evidence indicates that bacteria transiently shift their shapes into distinctive morphologies in response to environmental changes. Elongation of bacterial length into a filamentous shape provides unique survival advantages for many bacterial species. Analysis of 42 clinical isolates of uropathogenic <i>Escherichia coli</i> (UPEC) revealed that filamentation to host-derived antimicrobials is a conserved phenotype. Therefore, we hypothesize that filamentation represents a conserved mechanism of pathogenic bacterial persistence that can be targeted for narrow-spectrum, anti-virulence therapies. We demonstrate that cranberries prevent SulA-mediated filamentation of UPEC. Furthermore, we identify multiple fractions of cranberries that retain anti-filamentation properties. These studies provide mechanistic insight into the clinical efficacy of cranberry for patients with recurrent urinary tract infections. Inhibition of filamentation represents a novel approach to promote bacterial pathogen susceptibility to immune and antibiotic-mediated clearance to attenuate disease.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"93 5","pages":"e0060024"},"PeriodicalIF":2.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oral bacterium contributes to periodontal inflammation by forming advanced glycation end products. 口腔细菌通过形成晚期糖基化终产物导致牙周炎症。
IF 2.9 3区 医学
Infection and Immunity Pub Date : 2025-05-13 Epub Date: 2025-04-02 DOI: 10.1128/iai.00560-24
Rajendra P Settem, Ashu Sharma
{"title":"Oral bacterium contributes to periodontal inflammation by forming advanced glycation end products.","authors":"Rajendra P Settem, Ashu Sharma","doi":"10.1128/iai.00560-24","DOIUrl":"10.1128/iai.00560-24","url":null,"abstract":"<p><p>The oral bacterium <i>Tannerella forsythia</i> is associated with periodontitis, an inflammatory disease affecting tooth-supporting tissues. The bacterium produces a dicarbonyl compound, methylglyoxal (MGO), whose levels correlate with the severity of periodontitis. MGO can induce inflammation directly or via the generation of glycation products called advanced glycation end products (AGEs). <i>T. forsythia</i>-produced MGO has been shown to cause tissue collagen glycation, which in turn can induce pro-inflammatory cytokine secretion in monocytes via receptor for advanced glycation end product (RAGE) receptor activation. The current study investigated the impact of <i>T. forsythia</i>-secreted MGO on human gingival fibroblasts and endothelial cells. For assessing the <i>in vivo</i> impact of <i>T. forsythia</i>-secreted MGO, we employed an oral gavage-induced mouse model of periodontitis utilizing the wild-type and MGO-deficient strains of <i>T. forsythia</i>. Our results showed that the apoptotic activity was enhanced, and cell migration was reduced in fibroblasts exposed to collagen treated with the <i>T. forsythia</i> wild-type culture supernatant. Moreover, monocyte binding, reactive oxygen species production, and inflammatory cytokine secretion were increased in fibroblasts, and neutrophil transendothelial migration was enhanced in response to the <i>T. forsythia</i> wild type-treated collagen. <i>In vivo</i>, increased AGE accumulation in gingival tissues with increased alveolar bone loss was observed in wild-type <i>T. forsythia</i> as compared to the MGO-deficient strain-infected mice. These data demonstrated that <i>T. forsythia</i>-secreted MGO contributes to periodontal tissue destruction by mitigating gingival fibroblast-mediated tissue healing and promoting endothelial cell dysfunction. These findings provide a basis for targeting the <i>T. forsythia</i>-associated AGE-RAGE axis in alleviating periodontitis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0056024"},"PeriodicalIF":2.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Arginine utilization in Acinetobacter baumannii is essential for pneumonia pathogenesis and is regulated by virulence regulator GacA. 鲍曼不动杆菌对精氨酸的利用对肺炎发病至关重要,并受毒力调节剂GacA的调节。
IF 2.9 3区 医学
Infection and Immunity Pub Date : 2025-05-13 Epub Date: 2025-04-02 DOI: 10.1128/iai.00572-24
Kuldip Devnath, Avik Pathak, Perwez Bakht, Ranjana Pathania
{"title":"Arginine utilization in <i>Acinetobacter baumannii</i> is essential for pneumonia pathogenesis and is regulated by virulence regulator GacA.","authors":"Kuldip Devnath, Avik Pathak, Perwez Bakht, Ranjana Pathania","doi":"10.1128/iai.00572-24","DOIUrl":"10.1128/iai.00572-24","url":null,"abstract":"<p><p>Nutrient availability in infection niches and the ability of bacterial pathogens to alter their metabolic landscape to utilize diverse carbon sources play a major role in determining the extent of pathogenesis. The vertebrate lung is rich in amino acids, such as arginine, which are available to the pathogens as a nutrient source to establish infection. Arginine is also used by the host nitric oxide synthase to synthesize nitric oxide, which is used against invading pathogens and for lung tissue repair. In this study, we have focused on the arginine catabolic pathway and its importance in the pathophysiology of <i>Acinetobacter baumannii</i>, a nosocomial pathogen, which is one of the major causes of ventilator-associated pneumonia, catheter-associated urinary tract infection, and so on. We show that the arginine succinyltransferase (AST) pathway is the predominant arginine catabolic pathway in <i>A. baumannii</i>. The genes of the AST pathway are arranged in an operon and are conserved in <i>Acinetobacter</i> spp. We show that the deletion mutant of the AST pathway failed to utilize arginine as a carbon source, and its virulence was severely compromised in an <i>in vivo</i> murine pneumonia infection model. We identified GacA as the positive regulator of the AST operon in <i>A. baumannii</i>, which is different from other bacterial pathogens. Our study highlights the importance of arginine utilization in the pathophysiology and virulence of <i>A. baumannii</i>. Owing to its importance in the pathophysiology of <i>A. baumannii</i>, the arginine catabolic pathway can further be investigated to assess its suitability as an antibacterial drug target.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0057224"},"PeriodicalIF":2.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信