PLoS Pathogens最新文献

{"title":"A conserved fungal Knr4/Smi1 protein is crucial for maintaining cell wall stress tolerance and host plant pathogenesis.","authors":"Erika Kroll, Carlos Bayon, Jason Rudd, Victoria J Armer, Anjana Magaji-Umashankar, Ryan Ames, Martin Urban, Neil A Brown, Kim Hammond-Kosack","doi":"10.1371/journal.ppat.1012769","DOIUrl":"10.1371/journal.ppat.1012769","url":null,"abstract":"<p><p>Filamentous plant pathogenic fungi pose significant threats to global food security, particularly through diseases like Fusarium Head Blight (FHB) and Septoria Tritici Blotch (STB) which affects cereals. With mounting challenges in fungal control and increasing restrictions on fungicide use due to environmental concerns, there is an urgent need for innovative control strategies. Here, we present a comprehensive analysis of the stage-specific infection process of Fusarium graminearum in wheat spikes by generating a dual weighted gene co-expression network (WGCN). Notably, the network contained a mycotoxin-enriched fungal module (F12) that exhibited a significant correlation with a detoxification gene-enriched wheat module (W12). This correlation in gene expression was validated through quantitative PCR. By examining a fungal module with genes highly expressed during early symptomless infection that was correlated to a wheat module enriched in oxidative stress genes, we identified a gene encoding FgKnr4, a protein containing a Knr4/Smi1 disordered domain. Through comprehensive analysis, we confirmed the pivotal role of FgKnr4 in various biological processes, including oxidative stress tolerance, cell cycle stress tolerance, morphogenesis, growth, and pathogenicity. Further studies confirmed the observed phenotypes are partially due to the involvement of FgKnr4 in regulating the fungal cell wall integrity pathway by modulating the phosphorylation of the MAP-kinase MGV1. Orthologues of the FgKnr4 gene are widespread across the fungal kingdom but are absent in other Eukaryotes, suggesting the protein has potential as a promising intervention target. Encouragingly, the restricted growth and highly reduced virulence phenotypes observed for ΔFgknr4 were replicated upon deletion of the orthologous gene in the wheat fungal pathogen Zymoseptoria tritici. Overall, this study demonstrates the utility of an integrated network-level analytical approach to pinpoint genes of high interest to pathogenesis and disease control.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012769"},"PeriodicalIF":5.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines.","authors":"Zhaoling Shen, Cheng Li, Wenping Song, Litong Liu, Yu Kong, Ailing Huang, Qingui Bao, Tianlei Ying, Yanling Wu","doi":"10.1371/journal.ppat.1012845","DOIUrl":"10.1371/journal.ppat.1012845","url":null,"abstract":"<p><p>Vaccines are widely regarded as one of the most effective strategies for combating infectious diseases. However, significant challenges remain, such as insufficient antibody levels, limited protection against rapidly evolving variants, and poor immune durability, particularly in subunit vaccines, likely due to their short in vivo exposure. Recent advances in extending the half-life of protein therapeutics have shown promise in improving drug efficacy, yet whether increasing in vivo persistence can enhance the efficacy of subunit vaccines remains underexplored. In this study, we developed two trimeric SARS-CoV-2 subunit vaccines with distinct pharmacokinetic profiles to evaluate the impact of vaccine persistence on immune efficacy. A self-assembling trimeric subunit vaccine (RBD-HR/trimer) was designed, followed by an extended-persistence variant (RBD-sFc-HR/trimer) incorporating a soluble monomeric IgG1 fragment crystallizable. We demonstrated that RBD-sFc-HR/trimer elicited more robust and higher levels of neutralizing antibodies, with potent and broad neutralization activity against multiple SARS-CoV-2 variants. Notably, RBD-sFc-HR/trimer induced a durable immune response, significantly increasing the number of memory B cells and T cells. This study provides critical insights for designing vaccines that achieve potent and long-lasting immune responses against infectious diseases.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012845"},"PeriodicalIF":5.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An interferon-stimulated long non-coding RNA USP30-AS1 as an immune modulator in influenza A virus infection.","authors":"Yi Cao, Alex W H Chin, Haogao Gu, Mengting Li, Yuner Gu, Sylvia P N Lau, Kenrie P Y Hui, Michael C W Chan, Leo L M Poon","doi":"10.1371/journal.ppat.1012854","DOIUrl":"10.1371/journal.ppat.1012854","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are essential components of innate immunity, maintaining the functionality of immune systems that control virus infection. However, how lncRNAs engage immune responses during influenza A virus (IAV) infection remains unclear. Here, we show that lncRNA USP30-AS1 is up-regulated by infection of multiple different IAV subtypes and is required for tuning inflammatory and antiviral response in IAV infection. Genetically inactivation of USP30-AS1 enhances viral protein synthesis and viral growth. USP30-AS1 is an interferon-stimulated gene, and the induction of USP30-AS1 can be achieved by JAK-STAT mediated signaling activation. The immune regulation of USP30-AS1 is independent of its proximal protein-coding gene USP30. In IAV infection, deletion of USP30-AS1 unleashes high systemic inflammatory responses involving a broad range of pro-inflammatory factors, suggesting USP30-AS1 as a critical modulator of immune responses in IAV infection. Furthermore, we established a database providing well-annotated host gene expression profiles IAV infection or immune stimulation.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012854"},"PeriodicalIF":5.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FlbB forms a distinctive ring essential for periplasmic flagellar assembly and motility in Borrelia burgdorferi.","authors":"Jack M Botting, Md Khalesur Rahman, Hui Xu, Jian Yue, Wangbiao Guo, Joshua T Del Mundo, Michal Hammel, Md A Motaleb, Jun Liu","doi":"10.1371/journal.ppat.1012812","DOIUrl":"10.1371/journal.ppat.1012812","url":null,"abstract":"<p><p>Spirochetes are a widespread group of bacteria with a distinct morphology. Some spirochetes are important human pathogens that utilize periplasmic flagella to achieve motility and host infection. The motors that drive the rotation of periplasmic flagella have a unique spirochete-specific feature, termed the collar, crucial for the flat-wave morphology and motility of the Lyme disease spirochete Borrelia burgdorferi. Here, we deploy cryo-electron tomography and subtomogram averaging to determine high-resolution in-situ structures of the B. burgdorferi flagellar motor. Comparative analysis and molecular modeling of in-situ flagellar motor structures from B. burgdorferi mutants lacking each of the known collar proteins (FlcA, FlcB, FlcC, FlbB, and Bb0236/FlcD) uncover a complex protein network at the base of the collar. Importantly, our data suggest that FlbB forms a novel periplasmic ring around the rotor but also acts as a scaffold supporting collar assembly and subsequent recruitment of stator complexes. The complex protein network based on the FlbB ring effectively bridges the rotor and 16 torque-generating stator complexes in each flagellar motor, thus contributing to the specialized motility and lifestyle of spirochetes in complex environments.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012812"},"PeriodicalIF":5.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Widespread release of translational repression across Plasmodium's host-to-vector transmission event.","authors":"Kelly T Rios, James P McGee, Aswathy Sebastian, Sanjaya Aththawala Gedara, Robert L Moritz, Marina Feric, Sabrina Absalon, Kristian E Swearingen, Scott E Lindner","doi":"10.1371/journal.ppat.1012823","DOIUrl":"10.1371/journal.ppat.1012823","url":null,"abstract":"<p><p>Malaria parasites must respond quickly to environmental changes, including during their transmission between mammalian and mosquito hosts. Therefore, female gametocytes proactively produce and translationally repress mRNAs that encode essential proteins that the zygote requires to establish a new infection. While the release of translational repression of individual mRNAs has been documented, the details of the global release of translational repression have not. Moreover, changes in the spatial arrangement and composition of the DOZI/CITH/ALBA complex that contribute to translational control are also not known. Therefore, we have conducted the first quantitative, comparative transcriptomics and DIA-MS proteomics of Plasmodium parasites across the host-to-vector transmission event to document the global release of translational repression. Using female gametocytes and zygotes of P. yoelii, we found that ~200 transcripts are released for translation soon after fertilization, including those encoding essential functions. Moreover, we identified that many transcripts remain repressed beyond this point. TurboID-based proximity proteomics of the DOZI/CITH/ALBA regulatory complex revealed substantial spatial and/or compositional changes across this transmission event, which are consistent with recent, paradigm-shifting models of translational control. Together, these data provide a model for the essential translational control mechanisms that promote Plasmodium's efficient transmission from mammalian host to mosquito vector.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012823"},"PeriodicalIF":5.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key virulence factors responsible for differences in pathogenicity between clinically proven live-attenuated Japanese encephalitis vaccine SA14-14-2 and its pre-attenuated highly virulent parent SA14.","authors":"Byung-Hak Song, Sang-Im Yun, Joseph L Goldhardt, Jiyoun Kim, Young-Min Lee","doi":"10.1371/journal.ppat.1012844","DOIUrl":"10.1371/journal.ppat.1012844","url":null,"abstract":"<p><p>Japanese encephalitis virus (JEV), a neuroinvasive and neurovirulent orthoflavivirus, can be prevented in humans with the SA14-14-2 vaccine, a live-attenuated version derived from the wild-type SA14 strain. To determine the viral factors responsible for the differences in pathogenicity between SA14 and SA14-14-2, we initially established a reverse genetics system that includes a pair of full-length infectious cDNAs for both strains. Using this cDNA pair, we then systematically exchanged genomic regions between SA14 and SA14-14-2 to generate 20 chimeric viruses and evaluated their replication capability in cell culture and their pathogenic potential in mice. Our findings revealed the following: (i) The single envelope (E) protein of SA14-14-2, which contains nine mutations (eight in the ectodomain and one in the stem region), is both necessary and sufficient to render SA14 non-neuroinvasive and non-neurovirulent. (ii) Conversely, the E protein of SA14 alone is necessary for SA14-14-2 to become highly neurovirulent, but it is not sufficient to make it highly neuroinvasive. (iii) The limited neuroinvasiveness of an SA14-14-2 derivative that contains the E gene of SA14 significantly increases (approaching that of the wild-type strain) when two viral nonstructural proteins are replaced by their counterparts from SA14: (a) NS1/1', which has four mutations on the external surface of the core β-ladder domain; and (b) NS2A, which has two mutations in the N-terminal region, including two non-transmembrane α-helices. In line with their roles in viral pathogenicity, the E, NS1/1', and NS2A genes all contribute to the enhanced spread of the virus in cell culture. Collectively, our data reveal for the first time that the E protein of JEV has a dual function: It is the master regulator of viral neurovirulence and also the primary initiator of viral neuroinvasion. After the initial E-mediated neuroinvasion, the NS1/1' and NS2A proteins act as secondary promoters, further amplifying viral neuroinvasiveness.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012844"},"PeriodicalIF":5.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microsporidian Nosema bombycis secretes serine protease inhibitor to suppress host cell apoptosis via Caspase BmICE.","authors":"Maoshuang Ran, Jialing Bao, Boning Li, Yulian Shi, Wenxin Yang, Xianzhi Meng, Jie Chen, Junhong Wei, Mengxian Long, Tian Li, Chunfeng Li, Guoqing Pan, Zeyang Zhou","doi":"10.1371/journal.ppat.1012373","DOIUrl":"10.1371/journal.ppat.1012373","url":null,"abstract":"<p><p>Microsporidia are a group of intracellular pathogens that actively manipulate host cell biological processes to facilitate their intracellular niche. Apoptosis is an important defense mechanism by which host cell control intracellular pathogens. Microsporidia modulating host cell apoptosis has been reported previously, however the molecular mechanism is not yet clear. In this report, we describe that the microsporidia Nosema bombycis inhibits apoptosis of Bombyx mori cells through a secreted protein NbSPN14, which is a serine protease inhibitor (Serpin). An immunofluorescent assay demonstrated that upon infection with N. bombycis, NbSPN14 was initially found in the B. mori cell cytoplasm and then became enriched in the host cell nucleus. Overexpression and RNA-interference (RNAi) of NbSPN14 in B. mori' embryo cell confirmed that NbSPN14 inhibited host cells apoptosis. Immunofluorescent and Co-IP assays verified the co-localization and interaction of NbSPN14 with the BmICE, the Caspase 3 homolog in B. mori. Knocking out of BmICE or mutating the BmICE-interacting P1 site of NbSPN14, eliminated the localization of NbSPN14 into the host nucleus and prevented the apoptosis-inhibiting effect of NbSPN14, which also proved that the interaction between BmICE and NbSPN14 occurred in host cytoplasm and the NbSPN14 translocation into host cell nucleus depends on BmICE. These data elucidate that N. bombycis secretory protein NbSPN14 inhibits host cell apoptosis by directly inhibiting the Caspase protease BmICE, which provides an important insight for understanding pathogen-host interactions and a potential therapeutic target for N. bombycis proliferation.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012373"},"PeriodicalIF":5.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-species recognition of two porcine coronaviruses to their cellular receptor aminopeptidase N of dogs and seven other species.","authors":"Yuyang Tian, Junqing Sun, Xiaohan Hou, Zhimin Liu, Zeao Chen, Xiaoqian Pan, Ying Wang, Jianle Ren, Ding Zhang, Bo Yang, Longlong Si, Yuhai Bi, Kefang Liu, Guijun Shang, Wen-Xia Tian, Qihui Wang, George Fu Gao, Sheng Niu","doi":"10.1371/journal.ppat.1012836","DOIUrl":"10.1371/journal.ppat.1012836","url":null,"abstract":"<p><p>Porcine deltacoronavirus (PDCoV) and transmissible gastroenteritis coronavirus (TGEV), the two causative agents of porcine diarrhea, have been reported to be at risk of cross-species transmission, including to humans. However, the potential host range in which these two CoVs interact remains unclear. We screened 16 animal counterparts for porcine aminopeptidase N (APN), the receptor of PDCoV and TGEV, and found that APNs from eight of 17 animals could bind to the receptor-binding domains (RBDs) of PDCoV and TGEV. Furthermore, the animal APNs that could bind to the RBDs could mediate cellular infection by both viruses. Dog APN (dAPN) has been identified as the animal receptor with the highest capability to mediate the virus infection. We further resolved the complex structures of dAPN bound to the PDCoV RBD/TGEV RBD, respectively, establishing its divergent receptor-binding modes. We identified R325 of dAPN as an important residue in the PDCoV RBD-dAPN interaction, and found the central role of Q746 and T749 in dAPN in the interaction with the TGEV RBD. These findings provide the molecular basis of the potential cross-species transmission of these two porcine CoVs and shed light on future surveillance of these CoVs.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012836"},"PeriodicalIF":5.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2-induced cytokine storm drives prolonged testicular injury and functional impairment in mice that are mitigated by dexamethasone.","authors":"Stefanos Giannakopoulos, Jin Pak, Jackson Bakse, Monika A Ward, Vivek R Nerurkar, Michelle D Tallquist, Saguna Verma","doi":"10.1371/journal.ppat.1012804","DOIUrl":"10.1371/journal.ppat.1012804","url":null,"abstract":"<p><p>Compromised male reproductive health, including reduced testosterone and sperm count, is one of the long COVID symptoms in individuals recovering from mild-severe disease. COVID-19 patients display testicular injury in the acute stage and altered serum fertility markers in the recovery phase, however, long-term implications on the testis remain unknown. This study characterized the consequences of SARS-CoV-2 on testis function. The K18-hACE2 mice that survived SARS-CoV-2 infection were followed for one month after infection and the testicular injury and function markers were assessed at different stages of infection and recovery. The long-term impact of infection on key testes function-related hormones and male fertility was measured. The efficacy of inflammation-suppressing drug in preventing testicular injury was also evaluated. The morphological defects like sloughing of spermatids into the lumen and increased apoptotic cells sustained for 2-4 weeks after infection and correlated with testicular inflammation and immune cell infiltration. Transcriptomic analysis revealed dysregulation of inflammatory, cell death, and steroidogenic pathways. Furthermore, reduced testosterone levels associated with a transient reduction in sperm count and male fertility. Most testicular impairments resolved within one month of infection. Importantly, dexamethasone treatment attenuated testicular damage, inflammation, and immune infiltration. Our results implicate virus-induced cytokine storm as the major driver of testicular injury and functional impairments, timely prevention of which limits testis damage. These findings serve as a model for evaluating therapeutics in long COVID patients and may guide clinical strategies to improve male reproductive health outcomes post-SARS-CoV-2 infection.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012804"},"PeriodicalIF":5.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Avirulence depletion assay: Combining R gene-mediated selection with bulk sequencing for rapid avirulence gene identification in wheat powdery mildew.","authors":"Lukas Kunz, Jigisha Jigisha, Fabrizio Menardo, Alexandros G Sotiropoulos, Helen Zbinden, Shenghao Zou, Dingzhong Tang, Ralph Hückelhoven, Beat Keller, Marion C Müller","doi":"10.1371/journal.ppat.1012799","DOIUrl":"10.1371/journal.ppat.1012799","url":null,"abstract":"<p><p>Wheat production is threatened by multiple fungal pathogens, such as the wheat powdery mildew fungus (Blumeria graminis f. sp. tritici, Bgt). Wheat resistance breeding frequently relies on the use of resistance (R) genes that encode diverse immune receptors which detect specific avirulence (AVR) effectors and subsequently induce an immune response. While R gene cloning has accelerated recently, AVR identification in many pathogens including Bgt lags behind, preventing pathogen-informed deployment of resistance sources. Here we describe a new \"avirulence depletion (AD) assay\" for rapid identification of AVR genes in Bgt. This assay relies on the selection of a segregating, haploid F1 progeny population on a resistant host, followed by bulk sequencing, thereby allowing rapid avirulence candidate gene identification with high mapping resolution. In a proof-of-concept experiment we mapped the AVR component of the wheat immune receptor Pm3a to a 25 kb genomic interval in Bgt harboring a single effector, the previously described AvrPm3a2/f2. Subsequently, we applied the AD assay to map the unknown AVR effector recognized by the Pm60 immune receptor. We show that AvrPm60 is encoded by three tandemly arrayed, nearly identical effector genes that trigger an immune response upon co-expression with Pm60 and its alleles Pm60a and Pm60b. We furthermore provide evidence that Pm60 outperforms Pm60a and Pm60b through more efficient recognition of AvrPm60 effectors, suggesting it should be prioritized for wheat breeding. Finally, we show that virulence towards Pm60 is caused by simultaneous deletion of all AvrPm60 gene paralogs and that isolates lacking AvrPm60 are especially prevalent in the US thereby limiting the potential of Pm60 in this region. The AD assay is a powerful new tool for rapid and inexpensive AVR identification in Bgt with the potential to contribute to pathogen-informed breeding decisions for the use of novel R genes and regionally tailored gene deployment.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012799"},"PeriodicalIF":5.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}