Cell host & microbe最新文献_第5页

Intracellular acidification by microbiota-derived valeric acid facilitates trans-kingdom ecology limiting Candida parapsilosis colonization. 微生物群衍生的戊酸在细胞内的酸化促进了跨界生态，限制了假丝酵母的定植。

IF 18.7

Cell host & microbe Pub Date : 2026-07-08 Epub Date: 2026-06-04 DOI: 10.1016/j.chom.2026.05.008

Keiko Yasuma-Mitobe, Chen Liao, Tibor Németh, Kevin Byrne, Audrey Billips, Ruben Jose Jesus Faustino Ramos, Cristine Nicole Salinas, Eric Chan, Martina Perissinoto, Sophia Adami-Sampson, Ayesha Salman, Ashley M Sidebottom, George Plitas, Geraldine Butler, Justin R Cross, Eric G Pamer, Attila Gácser, Joao B Xavier, Tobias M Hohl

{"title":"Intracellular acidification by microbiota-derived valeric acid facilitates trans-kingdom ecology limiting Candida parapsilosis colonization.","authors":"Keiko Yasuma-Mitobe, Chen Liao, Tibor Németh, Kevin Byrne, Audrey Billips, Ruben Jose Jesus Faustino Ramos, Cristine Nicole Salinas, Eric Chan, Martina Perissinoto, Sophia Adami-Sampson, Ayesha Salman, Ashley M Sidebottom, George Plitas, Geraldine Butler, Justin R Cross, Eric G Pamer, Attila Gácser, Joao B Xavier, Tobias M Hohl","doi":"10.1016/j.chom.2026.05.008","DOIUrl":"10.1016/j.chom.2026.05.008","url":null,"abstract":"In hematopoietic cell transplant (HCT) patients, intestinal Candida parapsilosis expansion and translocation can cause life-threatening candidemia, yet whether commensal intestinal bacteria prevent Candida expansion remains incompletely defined. Here, we trained a machine learning model on supernatant metabolomic profiles of Lachnospiraceae to identify bacteria-derived inhibitors of fungal growth, identifying valeric and butyric acids as top hits. Fecal samples from HCT patients supported this association, with valeric and butyric acid levels inversely correlating with C. parapsilosis growth. In cell culture and mice, valeric acid inhibited C. parapsilosis growth by increasing intracellular acidification. Administration of glycerol valerate, or free or microencapsulated valeric acid, to release valeric acid along the entire intestinal tract blunted C. parapsilosis growth at murine intestinal sites where valeric acid was detected. Thus, machine learning identified a mechanistic driver of trans-kingdom ecology limiting C. parapsilosis intestinal expansion and may inform strategies to reduce patient risk of candidiasis.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1320-1332.e6"},"PeriodicalIF":18.7,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148165847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineering commensal microbes for host health. 为宿主健康设计共生微生物。

IF 18.7

Cell host & microbe Pub Date : 2026-07-08 DOI: 10.1016/j.chom.2026.05.025

Elizabeth A Brown, Arianna Brevi, David M Zong, Amir Zarrinpar

{"title":"Engineering commensal microbes for host health.","authors":"Elizabeth A Brown, Arianna Brevi, David M Zong, Amir Zarrinpar","doi":"10.1016/j.chom.2026.05.025","DOIUrl":"10.1016/j.chom.2026.05.025","url":null,"abstract":"Engineered live biotherapeutic products (eLBPs) represent an emerging class of programmable microbial therapies capable of sensing and responding to host physiology. Advances in microbiome science and synthetic biology have driven the development of engineered bacteria that deliver therapeutic molecules, modulate host metabolism, or detect disease-associated signals. In this review, we summarize recent progress in the development of eLBPs across diverse disease indications, including inflammatory diseases, metabolic disorders, cancer, and infectious diseases. We highlight key factors that drive successful eLBP design, including chassis selection, methods for DNA delivery, approaches for tuning therapeutic expression, and genetic systems for biocontainment. Although early clinical studies demonstrate promising safety profiles, challenges remain in achieving predictable colonization, durable therapeutic activity, and robust biocontainment in vivo. By synthesizing advances across these areas, we propose a framework for the rational design of next-generation eLBPs that can more reliably translate from experimental systems to clinical application.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":"34 7","pages":"1241-1261"},"PeriodicalIF":18.7,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148414100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Suppression of host salicylic acid defense by a phloem-colonizing pathogen effector in citrus Huanglongbing. 一种韧皮部定殖病原菌效应物对柑桔水杨酸防御的抑制作用。

IF 18.7

Cell host & microbe Pub Date : 2026-07-08 Epub Date: 2026-06-19 DOI: 10.1016/j.chom.2026.05.026

Bin Hu, Tao Yuan, Rongyan Huang, Yuantao Xu, Shengjie Lin, Jingchao Lv, Kun Yang, Qinchun Wu, Gang Hu, Zhihao Lu, Chunyang He, Wang Zhang, Changxiu Xia, Xiang Yan, Ping Yin, Xia Wang, Xiuxin Deng, Fang Ding, Qiang Xu

{"title":"Suppression of host salicylic acid defense by a phloem-colonizing pathogen effector in citrus Huanglongbing.","authors":"Bin Hu, Tao Yuan, Rongyan Huang, Yuantao Xu, Shengjie Lin, Jingchao Lv, Kun Yang, Qinchun Wu, Gang Hu, Zhihao Lu, Chunyang He, Wang Zhang, Changxiu Xia, Xiang Yan, Ping Yin, Xia Wang, Xiuxin Deng, Fang Ding, Qiang Xu","doi":"10.1016/j.chom.2026.05.026","DOIUrl":"10.1016/j.chom.2026.05.026","url":null,"abstract":"Citrus Huanglongbing (HLB), caused by Candidatus Liberibacter asiaticus (CLas), severely threatens citrus production. Here, we identify Sec-delivered effector 10 (SDE10), a key effector from CLas, whose ectopic expression in citrus mimics HLB symptoms. Genetic and biochemical analyses demonstrate that SDE10 suppresses salicylic acid (SA)-mediated defense by inhibiting xylem cysteine peptidase 2 (CsXCP2). CsXCP2 positively regulates SA homeostasis through two activity-dependent mechanisms. First, it processes pathogenesis-related 1 (CsPR1) to generate cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP)-derived peptide 9 (CsCAPE9), which activates SA-mediated defense and significantly reduces CLas titers under both greenhouse and field conditions. Second, it degrades the CLas-derived SA hydroxylase (SahA), thereby preventing SA signaling disruption. Notably, engineered CsXCP2 variants that evade SDE10 binding while retaining moderate activity can counteract SDE10-mediated defense suppression. Collectively, our findings delineate a sophisticated molecular arms race between CLas virulence strategies and citrus immune countermeasures centered on SA signaling modulation, providing a mechanistic foundation for breeding HLB-resistant citrus varieties.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1415-1429.e9"},"PeriodicalIF":18.7,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148285063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An acidic welcome: How microbial metabolites keep fungi in line. 酸性的欢迎：微生物代谢物如何使真菌保持有序。

IF 18.7

Cell host & microbe Pub Date : 2026-07-08 DOI: 10.1016/j.chom.2026.06.011

Marienela Y Heredia, Gustavo Caballero-Flores

引用次数: 0

Toward precision microbiome therapeutics: From black box to blueprint. 迈向精确的微生物组治疗：从黑盒到蓝图。

IF 18.7

Cell host & microbe Pub Date : 2026-07-08 DOI: 10.1016/j.chom.2026.06.014

Diego Rivera Gelsinger, Harris H Wang

引用次数: 0

Predicting antimicrobial resistance for precision medicine. 预测精准医疗的抗菌素耐药性。

IF 18.7

Cell host & microbe Pub Date : 2026-07-08 Epub Date: 2026-06-26 DOI: 10.1016/j.chom.2026.05.031

Theresa Fink, Jan Rybniker, Tobias Bollenbach

引用次数: 0

Sweet and sour immunity: The two faces of citrus defense in Huanglongbing. 酸甜免疫：黄龙冰柑橘防御的两面。

IF 18.7

Cell host & microbe Pub Date : 2026-07-08 DOI: 10.1016/j.chom.2026.06.012

Chien-Yu Huang

引用次数: 0

Meta-analysis reveals microbiome signatures for colorectal cancer that are universal across age groups and sequencing methods. 荟萃分析显示，结直肠癌的微生物组特征在不同年龄组和测序方法中都是普遍的。

IF 18.7

Cell host & microbe Pub Date : 2026-07-08 Epub Date: 2026-06-24 DOI: 10.1016/j.chom.2026.05.030

Selin Pekel, Nicolai Karcher, Morgan Essex, Fabian Springer, Stefano Romano, Quinten R Ducarmon, Christian Schudoma, Martin Larralde, Alberto Lupatin, Sebastian Zeissig, Michael Zimmermann, Georg Zeller

{"title":"Meta-analysis reveals microbiome signatures for colorectal cancer that are universal across age groups and sequencing methods.","authors":"Selin Pekel, Nicolai Karcher, Morgan Essex, Fabian Springer, Stefano Romano, Quinten R Ducarmon, Christian Schudoma, Martin Larralde, Alberto Lupatin, Sebastian Zeissig, Michael Zimmermann, Georg Zeller","doi":"10.1016/j.chom.2026.05.030","DOIUrl":"10.1016/j.chom.2026.05.030","url":null,"abstract":"Numerous studies have linked gut microbiome alterations to colorectal cancer (CRC), but limited sample sizes and study heterogeneity have hampered cross-study comparisons and subgroup analyses. Here, we present a comprehensive single-disease gut microbiome meta-analysis based on consistently re-computed and re-analyzed shotgun and amplicon sequencing profiles (n = 6,779 samples, 27 studies). Association and machine-learning analyses delineate CRC microbiome signatures, which are robustly generalizable across studies and sequencing approaches and nearly identical between early- and late-onset cases. Meta-analysis of the tumor-resident microbiome reveals characteristic tumor-enriched microbes in concordance with fecal signatures that are clearly detectable in early-stage tumors, although their detection in feces becomes moderately higher in late-stage and distal tumors, possibly due to dilution effects in stool. The unified fecal CRC signature inversely associates with dietary fiber intake and is modifiable by dietary interventions. Finally, genome-resolved functional analysis reveals variation in virulence factor carriage and geographic enrichment across Fusobacterium subspecies.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1462-1476.e5"},"PeriodicalIF":18.7,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mining the code of life for new antibiotics. 挖掘新的抗生素的生命密码。

IF 18.7

Cell host & microbe Pub Date : 2026-07-08 DOI: 10.1016/j.chom.2026.06.007

Anna Crysler, Cesar de la Fuente-Nunez

{"title":"Mining the code of life for new antibiotics.","authors":"Anna Crysler, Cesar de la Fuente-Nunez","doi":"10.1016/j.chom.2026.06.007","DOIUrl":"https://doi.org/10.1016/j.chom.2026.06.007","url":null,"abstract":"Antimicrobial resistance (AMR) is outpacing antibiotic development, creating an urgent need for discovery strategies that are faster, broader, and more systematic. Here, we review the transition from classical \"dirt mining\" and phenotypic screening toward digital discovery approaches that treat chemical structures and biological sequences as searchable, engineerable substrates for antibiotic innovation. Modern extensions of conventional screening, including in situ cultivation, co-culture, and microfluidics, have broadened access to previously uncultured microbes. Computer-aided approaches spanning virtual screening, molecular networking, and deep learning have enabled identification of unconventional antibacterial scaffolds from ultra-large chemical libraries. Mining genomes, proteomes, and metagenomes has uncovered antimicrobial peptides, encrypted peptides, and biosynthetic gene clusters encoding novel small-molecule antibiotics. Generative AI now enables design of peptides and small molecules under multiobjective constraints, including potency, toxicity, stability, and resistance risk. Together, these advances point toward discovery platforms that improve novelty, hit rates, and long-term durability in the face of AMR.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":"34 7","pages":"1273-1284"},"PeriodicalIF":18.7,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148414211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A fungal pathobiont promotes Streptococcus vaginal persistence and pathogenesis through physical and metabolic interactions. 一种真菌病原体通过物理和代谢的相互作用促进链球菌的阴道持久性和发病机制。

IF 18.7

Cell host & microbe Pub Date : 2026-06-10 Epub Date: 2026-05-13 DOI: 10.1016/j.chom.2026.04.013

Shirli Cohen, Arianne J Crossen, Owen Jensen, Melody N Neely, Kirsty Le Doare, Angela H Nobbs, Kyla S Ost, Kelly S Doran

{"title":"A fungal pathobiont promotes Streptococcus vaginal persistence and pathogenesis through physical and metabolic interactions.","authors":"Shirli Cohen, Arianne J Crossen, Owen Jensen, Melody N Neely, Kirsty Le Doare, Angela H Nobbs, Kyla S Ost, Kelly S Doran","doi":"10.1016/j.chom.2026.04.013","DOIUrl":"10.1016/j.chom.2026.04.013","url":null,"abstract":"Group B Streptococcus (GBS) frequently colonizes the vagina asymptomatically, where the bacterium interacts with a complex microbial community. During pregnancy, colonization can trigger adverse outcomes and neonatal invasive infection. Using an adapted murine model of vaginal colonization, we show that the human pathobiont Candida albicans supports GBS fitness in the vaginal tract and ascension to the uterus. C. albicans positively associates with GBS across several human studies, and C. albicans and GBS physically interact in a mouse co-colonization model. This co-colonization contributes to GBS persistence in the vagina, cervix, and uterus and facilitates antibiotic evasion. Across clinical isolates, the hyphal form of C. albicans promotes GBS aggregation and adhesion to host epithelial cells. Contact with GBS induces arginine biosynthesis in C. albicans, which drives bacterial virulence gene expression and primes GBS adhesion. These findings show that interkingdom nutrient exchange can increase GBS pathogenic potential and highlight targets for preventive therapies.","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1118-1134.e7"},"PeriodicalIF":18.7,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0