Edward B. Irvine, Angel Nikolov, Mehak Z. Khan, Joshua M. Peters, Richard Lu, Jaimie Sixsmith, Aaron Wallace, Esther van Woudenbergh, Sally Shin, Wiktor Karpinski, Jeff C. Hsiao, Arturo Casadevall, Bryan D. Bryson, Lisa Cavacini, Patricia S. Grace, Galit Alter, Sarah M. Fortune
{"title":"Fc-engineered antibodies promote neutrophil-dependent control of Mycobacterium tuberculosis","authors":"Edward B. Irvine, Angel Nikolov, Mehak Z. Khan, Joshua M. Peters, Richard Lu, Jaimie Sixsmith, Aaron Wallace, Esther van Woudenbergh, Sally Shin, Wiktor Karpinski, Jeff C. Hsiao, Arturo Casadevall, Bryan D. Bryson, Lisa Cavacini, Patricia S. Grace, Galit Alter, Sarah M. Fortune","doi":"10.1038/s41564-024-01777-9","DOIUrl":"10.1038/s41564-024-01777-9","url":null,"abstract":"Mounting evidence indicates that antibodies can contribute towards control of tuberculosis (TB). However, the underlying mechanisms of humoral immune protection and whether antibodies can be exploited in therapeutic strategies to combat TB are relatively understudied. Here we engineered the receptor-binding Fc (fragment crystallizable) region of an antibody recognizing the Mycobacterium tuberculosis (Mtb) capsule, to define antibody Fc-mediated mechanism(s) of Mtb restriction. We generated 52 Fc variants that either promote or inhibit specific antibody effector functions, rationally building antibodies with enhanced capacity to promote Mtb restriction in a human whole-blood model of infection. While there is likely no singular Fc profile that universally drives control of Mtb, here we found that several Fc-engineered antibodies drove Mtb restriction in a neutrophil-dependent manner. Single-cell RNA sequencing analysis showed that a restrictive Fc-engineered antibody promoted neutrophil survival and expression of cell-intrinsic antimicrobial programs. These data show the potential of Fc-engineered antibodies as therapeutics able to harness the protective functions of neutrophils to promote control of TB. Fc engineering of a capsule-specific antibody identifies Fc variants which augment effector function and promote neutrophil-dependent control of Mycobacterium tuberculosis.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2369-2382"},"PeriodicalIF":20.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01777-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142022070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The adhesin RadD enhances Fusobacterium nucleatum tumour colonization and colorectal carcinogenesis","authors":"Lu Zhang, Xiao-Xu Leng, Jianxun Qi, Ni Wang, Ji-Xuan Han, Zhi-Hang Tao, Zi-Yan Zhuang, Yimeng Ren, Yi-Le Xie, Shan-Shan Jiang, Jia-Lu Li, Huimin Chen, Cheng-Bei Zhou, Yun Cui, Xiaoyu Chen, Zheng Wang, Zi-Zhen Zhang, Jie Hong, Hao-Yan Chen, Weihong Jiang, Ying-Xuan Chen, Xin Zhao, Jun Yu, Jing-Yuan Fang","doi":"10.1038/s41564-024-01784-w","DOIUrl":"10.1038/s41564-024-01784-w","url":null,"abstract":"Fusobacterium nucleatum can bind to host cells and potentiate intestinal tumorigenesis. Here we used a genome-wide screen to identify an adhesin, RadD, which facilitates the attachment of F. nucleatum to colorectal cancer (CRC) cells in vitro. RadD directly binds to CD147, a receptor overexpressed on CRC cell surfaces, which initiated a PI3K–AKT–NF–κB–MMP9 cascade, subsequently enhancing tumorigenesis in mice. Clinical specimen analysis showed that elevated radD gene levels in CRC tissues correlated positively with activated oncogenic signalling and poor patient outcomes. Finally, blockade of the interaction between RadD and CD147 in mice effectively impaired F. nucleatum attachment and attenuated F. nucleatum-induced oncogenic response. Together, our study provides insights into an oncogenic mechanism driven by F. nucleatum RadD and suggests that the RadD–CD147 interaction could be a potential therapeutic target for CRC. The bacterial adhesin, RadD, enhances the ability of Fusobacterium nucleatum to interact with colorectal cancer cells and promote tumour development in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2292-2307"},"PeriodicalIF":20.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bacteria induce metabolic perturbations in ticks","authors":"W. Robert Shaw, Flaminia Catteruccia","doi":"10.1038/s41564-024-01787-7","DOIUrl":"10.1038/s41564-024-01787-7","url":null,"abstract":"A metabolomics approach to study microbe–tick interactions reveals that host β-aminoisobutyric acid contributes both to tick fitness and bacterial infection.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2206-2207"},"PeriodicalIF":20.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yaohui Sun, Fernando Ferreira, Brian Reid, Kan Zhu, Li Ma, Briana M. Young, Catherine E. Hagan, Renée M. Tsolis, Alex Mogilner, Min Zhao
{"title":"Gut epithelial electrical cues drive differential localization of enterobacteria","authors":"Yaohui Sun, Fernando Ferreira, Brian Reid, Kan Zhu, Li Ma, Briana M. Young, Catherine E. Hagan, Renée M. Tsolis, Alex Mogilner, Min Zhao","doi":"10.1038/s41564-024-01778-8","DOIUrl":"10.1038/s41564-024-01778-8","url":null,"abstract":"Salmonella translocate to the gut epithelium via microfold cells lining the follicle-associated epithelium (FAE). How Salmonella localize to the FAE is not well characterized. Here we use live imaging and competitive assays between wild-type and chemotaxis-deficient mutants to show that Salmonella enterica serotype Typhimurium (S. Typhimurium) localize to the FAE independently of chemotaxis in an ex vivo mouse caecum infection model. Electrical recordings revealed polarized FAE with sustained outward current and small transepithelial potential, while the surrounding villus is depolarized with inward current and large transepithelial potential. The distinct electrical potentials attracted S. Typhimurium to the FAE while Escherichia coli (E. coli) localized to the villi, through a process called galvanotaxis. Chloride flux involving the cystic fibrosis transmembrane conductance regulator (CFTR) generated the ionic currents around the FAE. Pharmacological inhibition of CFTR decreased S. Typhimurium FAE localization but increased E. coli recruitment. Altogether, our findings demonstrate that bioelectric cues contribute to S. Typhimurium targeting of specific gut epithelial locations, with potential implications for other enteric bacterial infections. Gut epithelium generated electrical potentials drive differential localization of enterobacteria, promoting Salmonella tropism for the follicle-associated epithelium while Escherichia coli localize to villi.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 10","pages":"2653-2665"},"PeriodicalIF":20.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01778-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yassine Cherrak, Miguel Angel Salazar, Nicolas Näpflin, Lukas Malfertheiner, Mathias K.-M. Herzog, Christopher Schubert, Christian von Mering, Wolf-Dietrich Hardt
{"title":"Non-canonical start codons confer context-dependent advantages in carbohydrate utilization for commensal E. coli in the murine gut","authors":"Yassine Cherrak, Miguel Angel Salazar, Nicolas Näpflin, Lukas Malfertheiner, Mathias K.-M. Herzog, Christopher Schubert, Christian von Mering, Wolf-Dietrich Hardt","doi":"10.1038/s41564-024-01775-x","DOIUrl":"10.1038/s41564-024-01775-x","url":null,"abstract":"Resource competition is a driver of gut microbiota composition. Bacteria can outcompete metabolically similar rivals through the limitation of shared growth-fuelling nutrients. The mechanisms underlying this remain unclear for bacteria with identical sets of metabolic genes. Here we analysed the lactose utilization operon in the murine commensal Escherichia coli 8178. Using in vitro and in vivo approaches, we showed that translation of the lactose utilization repressor gene lacI from its native non-canonical GTG start codon increases the basal expression of the lactose utilization cluster, enhancing adaptation to lactose consumption. Consequently, a strain carrying the wild type lacI GTG start codon outperformed the lacI ATG start codon mutant in the mouse intestine. This advantage was attenuated upon limiting host lactose intake through diet shift or altering the mutant frequency, emphasizing the context-dependent effect of a single nucleotide change on the bacterial fitness of a common member of the gut microbiota. Coupled with a genomic analysis highlighting the selection of non-ATG start codons in sugar utilization regulator genes across the Enterobacteriaceae family, our data exposed an unsuspected function of non-canonical start codons in metabolic competition. Non-canonical start codons promote carbohydrate exploitation and faster metabolic adaptation, conferring growth advantages to commensal Escherichia coli in the mouse gut.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 10","pages":"2696-2709"},"PeriodicalIF":20.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01775-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Host–gut microbiota crosstalk predicts neuroinflammation","authors":"Carolina M. Polonio, Francisco J. Quintana","doi":"10.1038/s41564-024-01790-y","DOIUrl":"10.1038/s41564-024-01790-y","url":null,"abstract":"Microbial networks and host–microbiota interactions, especially immunoglobulin A coating of resident microbiota, outperform bacterial abundance as a predictor of neuroinflammation severity in a mouse model of multiple sclerosis.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2204-2205"},"PeriodicalIF":20.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evolutionary origin of the tropical race 4 banana pathogen and mechanisms of its virulence","authors":"","doi":"10.1038/s41564-024-01783-x","DOIUrl":"10.1038/s41564-024-01783-x","url":null,"abstract":"Fusarium oxysporum f. sp. cubense tropical race 4 is threatening worldwide banana production. This study revealed a distinct evolutionary origin of tropical race 4 and how accessory genes and nitrosative pressure may have provided potential weaponries used by the pathogen to infect banana plants.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2212-2213"},"PeriodicalIF":20.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Virulence of banana wilt-causing fungal pathogen Fusarium oxysporum tropical race 4 is mediated by nitric oxide biosynthesis and accessory genes","authors":"Yong Zhang, Siwen Liu, Diane Mostert, Houlin Yu, Mengxia Zhuo, Gengtan Li, Cunwu Zuo, Sajeet Haridas, Katie Webster, Minhui Li, Igor V. Grigoriev, Ganjun Yi, Altus Viljoen, Chunyu Li, Li-Jun Ma","doi":"10.1038/s41564-024-01779-7","DOIUrl":"10.1038/s41564-024-01779-7","url":null,"abstract":"Fusarium wilt of banana, caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most damaging plant diseases known. Foc race 1 (R1) decimated the Gros Michel-based banana (Musa acuminata) trade, and now Foc tropical race 4 (TR4) threatens global production of its replacement, the Cavendish banana. Here population genomics revealed that all Cavendish banana-infecting Foc race 4 strains share an evolutionary origin distinct from that of R1 strains. Although TR4 lacks accessory chromosomes, it contains accessory genes at the ends of some core chromosomes that are enriched for virulence and mitochondria-related functions. Meta-transcriptomics revealed the unique induction of the entire mitochondrion-localized nitric oxide (NO) biosynthesis pathway upon TR4 infection. Empirically, we confirmed the unique induction of a NO burst in TR4, suggesting that nitrosative pressure may contribute to virulence. Targeted mutagenesis demonstrated the functional importance of fungal NO production and the accessory gene SIX4 as virulence factors. Population genomics and meta-transcriptomics reveal a role of nitric oxide production and accessory genes in the virulence of the banana wilt-causing fungal pathogen Fusarium oxysporum.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2232-2243"},"PeriodicalIF":20.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Translating between science and politics as a government adviser","authors":"Robin C. May","doi":"10.1038/s41564-024-01776-w","DOIUrl":"10.1038/s41564-024-01776-w","url":null,"abstract":"Moving from academia to government was challenging, but learning to translate evidence-based results into policy decisions that impact society is hugely rewarding, writes Robin May.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2202-2203"},"PeriodicalIF":20.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yun Deng, Ruyi Yu, Veit Grabe, Thomas Sommermann, Markus Werner, Marine Vallet, Christian Zerfaß, Oliver Werz, Georg Pohnert
{"title":"Bacteria modulate microalgal aging physiology through the induction of extracellular vesicle production to remove harmful metabolites","authors":"Yun Deng, Ruyi Yu, Veit Grabe, Thomas Sommermann, Markus Werner, Marine Vallet, Christian Zerfaß, Oliver Werz, Georg Pohnert","doi":"10.1038/s41564-024-01746-2","DOIUrl":"10.1038/s41564-024-01746-2","url":null,"abstract":"The bloom and bust patterns of microalgae in aquatic systems contribute massively to global biogeochemical cycles. The decline of algal blooms is mainly caused by nutrient limitation resulting in cell death, the arrest of cell division and the aging of surviving cells. Nutrient intake can re-initiate proliferation, but the processes involved are poorly understood. Here we characterize how the bloom-forming diatom Coscinodiscus radiatus recovers from starvation after nutrient influx. Rejuvenation is mediated by extracellular vesicles that shuttle reactive oxygen species, oxylipins and other harmful metabolites out of the old cells, thereby re-enabling their proliferation. By administering nutrient pulses to aged cells and metabolomic monitoring of the response, we show that regulated pathways are centred around the methionine cycle in C. radiatus. Co-incubation experiments show that bacteria mediate aging processes and trigger vesicle production using chemical signalling. This work opens new perspectives on cellular aging and rejuvenation in complex microbial communities. The release of vesicles that shuttle harmful metabolites out of aging cells of the bloom-forming Coscinodiscus radiatus is modulated by bacteria.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 9","pages":"2356-2368"},"PeriodicalIF":20.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01746-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}