PLoS GeneticsPub Date : 2024-10-28eCollection Date: 2024-10-01DOI: 10.1371/journal.pgen.1011448
Bayan Kharrat, Erika Gábor, Nikolett Virág, Rita Sinka, Ferenc Jankovics, Ildikó Kristó, Péter Vilmos, Gábor Csordás, Viktor Honti
{"title":"Dual role for Headcase in hemocyte progenitor fate determination in Drosophila melanogaster.","authors":"Bayan Kharrat, Erika Gábor, Nikolett Virág, Rita Sinka, Ferenc Jankovics, Ildikó Kristó, Péter Vilmos, Gábor Csordás, Viktor Honti","doi":"10.1371/journal.pgen.1011448","DOIUrl":"10.1371/journal.pgen.1011448","url":null,"abstract":"<p><p>The hematopoietic organ of the Drosophila larva, the lymph gland, is a simplified representation of mammalian hematopoietic compartments, with the presence of hemocyte progenitors in the medullary zone (MZ), differentiated hemocytes in the cortical zone (CZ), and a hematopoietic niche called the posterior signaling centre (PSC) that orchestrates progenitor differentiation. Our previous work has demonstrated that the imaginal cell factor Headcase (Hdc, Heca) is required in the hematopoietic niche to control the differentiation of hemocyte progenitors. However, the downstream mechanisms of Hdc-mediated hematopoietic control remained unknown. Here we show that Hdc exerts this function by negatively regulating the insulin/mTOR signaling in the niche. When Hdc is depleted in the PSC, the overactivation of this pathway triggers reactive oxygen species (ROS) accumulation and, in turn, the differentiation of effector lamellocytes non-cell-autonomously. Although overactivation of insulin/mTOR signaling normally leads to an increase in the size of the hematopoietic niche, this effect is concealed by cell death caused by hdc loss-of-function. Moreover, we describe here that hdc silencing in progenitors causes cell-autonomous ROS elevation and JNK pathway activation, resulting in decreased MZ size and differentiation of lamellocytes. Similarly to the PSC niche, knocking down hdc in the MZ also leads to caspase activation. Notably, depleting Hdc in the progenitors triggers proliferation, an opposing effect to what is observed in the niche. These findings further our understanding of how progenitor maintenance in the larval lymph gland is controlled autonomously and non-cell-autonomously, and point towards new mechanisms potentially regulating HSC maintenance across vertebrates.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 10","pages":"e1011448"},"PeriodicalIF":4.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS GeneticsPub Date : 2024-10-25eCollection Date: 2024-10-01DOI: 10.1371/journal.pgen.1011452
Petros Skiadas, Sofía Riera Vidal, Joris Dommisse, Melanie N Mendel, Joyce Elberse, Guido Van den Ackerveken, Ronnie de Jonge, Michael F Seidl
{"title":"Pangenome graph analysis reveals extensive effector copy-number variation in spinach downy mildew.","authors":"Petros Skiadas, Sofía Riera Vidal, Joris Dommisse, Melanie N Mendel, Joyce Elberse, Guido Van den Ackerveken, Ronnie de Jonge, Michael F Seidl","doi":"10.1371/journal.pgen.1011452","DOIUrl":"10.1371/journal.pgen.1011452","url":null,"abstract":"<p><p>Plant pathogens adapt at speeds that challenge contemporary disease management strategies like the deployment of disease resistance genes. The strong evolutionary pressure to adapt, shapes pathogens' genomes, and comparative genomics has been instrumental in characterizing this process. With the aim to capture genomic variation at high resolution and study the processes contributing to adaptation, we here leverage an innovative, multi-genome method to construct and annotate the first pangenome graph of an oomycete plant pathogen. We expand on this approach by analysing the graph and creating synteny based single-copy orthogroups for all genes. We generated telomere-to-telomere genome assemblies of six genetically diverse isolates of the oomycete pathogen Peronospora effusa, the economically most important disease in cultivated spinach worldwide. The pangenome graph demonstrates that P. effusa genomes are highly conserved, both in chromosomal structure and gene content, and revealed the continued activity of transposable elements which are directly responsible for 80% of the observed variation between the isolates. While most genes are generally conserved, virulence related genes are highly variable between the isolates. Most of the variation is found in large gene clusters resulting from extensive copy-number expansion. Pangenome graph-based discovery can thus be effectively used to capture genomic variation at exceptional resolution, thereby providing a framework to study the biology and evolution of plant pathogens.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 10","pages":"e1011452"},"PeriodicalIF":4.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS GeneticsPub Date : 2024-10-25eCollection Date: 2024-10-01DOI: 10.1371/journal.pgen.1011454
H Auguste Dutcher, James Hose, Hollis Howe, Julie Rojas, Audrey P Gasch
{"title":"The response to single-gene duplication implicates translation as a key vulnerability in aneuploid yeast.","authors":"H Auguste Dutcher, James Hose, Hollis Howe, Julie Rojas, Audrey P Gasch","doi":"10.1371/journal.pgen.1011454","DOIUrl":"10.1371/journal.pgen.1011454","url":null,"abstract":"<p><p>Aneuploidy produces myriad consequences in health and disease, yet models of the deleterious effects of chromosome amplification are still widely debated. To distinguish the molecular determinants of aneuploidy stress, we measured the effects of duplicating individual genes in cells with different chromosome duplications, in wild-type cells (SSD1+) and cells sensitized to aneuploidy by deletion of RNA-binding protein Ssd1 (ssd1Δ). We identified gene duplications that are nearly neutral in wild-type euploid cells but significantly deleterious in euploids lacking SSD1 or in SSD1+ aneuploid cells with different chromosome duplications. Several of the most deleterious genes are linked to translation. In contrast, duplication of other genes benefits multiple ssd1Δ aneuploids over controls, and this group is enriched for translational effectors. Furthermore, both wild-type and especially ssd1Δ aneuploids with different chromosome amplifications show increased sensitivity to translational inhibitor nourseothricin. We used comparative modeling of aneuploid growth defects, based on the cumulative fitness costs measured for single-gene duplication. Our results present a model in which the deleterious effects of aneuploidy emerge from an interaction between the cumulative burden of many amplified genes on a chromosome and a subset of duplicated genes that become toxic in that context. These findings provide a perspective on the dual impact of individual genes and overall genomic burden, offering new avenues for understanding aneuploidy and its cellular consequences.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 10","pages":"e1011454"},"PeriodicalIF":4.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS GeneticsPub Date : 2024-10-24eCollection Date: 2024-10-01DOI: 10.1371/journal.pgen.1011459
Nguyen Thi Khanh Nhu, Brian M Forde, Nouri L Ben Zakour, Minh-Duy Phan, Leah W Roberts, Scott A Beatson, Mark A Schembri
{"title":"Evolution of the pheV-tRNA integrated genomic island in Escherichia coli.","authors":"Nguyen Thi Khanh Nhu, Brian M Forde, Nouri L Ben Zakour, Minh-Duy Phan, Leah W Roberts, Scott A Beatson, Mark A Schembri","doi":"10.1371/journal.pgen.1011459","DOIUrl":"10.1371/journal.pgen.1011459","url":null,"abstract":"<p><p>Escherichia coli exhibit extensive genetic diversity at the genome level, particularly within their accessory genome. The tRNA integrated genomic islands (GIs), a part of the E. coli accessory genome, play an important role in pathogenicity. However, studies examining the evolution of GIs have been challenging due to their large size, considerable gene content variation and fragmented assembly in draft genomes. Here we examined the evolution of the GI integrated at pheV-tRNA (GI-pheV), with a primary focus on uropathogenic E. coli (UPEC) and the globally disseminated multidrug resistant ST131 clone. We show the gene content of GI-pheV is highly diverse and arranged in a modular configuration, with the P4 integrase encoding gene intP4 the only conserved gene. Despite this diversity, the GI-pheV gene content displayed conserved features among strains from the same pathotype. In ST131, GI-pheV corresponding to the reference strain EC958 (EC958_GI-pheV) was found in ~90% of strains. Phylogenetic analyses suggested that GI-pheV in ST131 has evolved together with the core genome, with the loss/gain of specific modules (or the entire GI) linked to strain specific events. Overall, we show GI-pheV exhibits a dynamic evolutionary pathway, in which modules and genes have evolved through multiple events including insertions, deletions and recombination.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 10","pages":"e1011459"},"PeriodicalIF":4.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS GeneticsPub Date : 2024-10-24eCollection Date: 2024-10-01DOI: 10.1371/journal.pgen.1011434
Ayana L Henderson, Rajendiran Karthikraj, Emma L Berdan, Shannan Ho Sui, Kurunthachalam Kannan, Monica P Colaiácovo
{"title":"Exposure to benzyl butyl phthalate (BBP) leads to increased double-strand break formation and germline dysfunction in Caenorhabditis elegans.","authors":"Ayana L Henderson, Rajendiran Karthikraj, Emma L Berdan, Shannan Ho Sui, Kurunthachalam Kannan, Monica P Colaiácovo","doi":"10.1371/journal.pgen.1011434","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011434","url":null,"abstract":"<p><p>Benzyl butyl phthalate (BBP), a plasticizer found in a wide range of consumer products including vinyl flooring, carpet backing, food packaging, personal care products, and children's toys, is an endocrine-disrupting chemical linked to impaired reproduction and development in humans. Despite evidence that BBP exposure perturbs the integrity of male and female gametes, its direct effect on early meiotic events is understudied. Here, using the nematode Caenorhabditis elegans, we show that BBP exposure elicits a non-monotonic dose response on the rate of X-chromosome nondisjunction measured using a high-throughput screening platform. From among the range of doses tested (1, 10, 100 and 500 μM BBP), we found that 10 μM BBP elicited the strongest effect on the germline, resulting in increased germ cell apoptosis and chromosome organization defects. Mass spectrometry analysis shows that C. elegans efficiently metabolizes BBP into its primary metabolites, monobutyl phthalate (MBP) and monobenzyl phthalate (MBzP), and that the levels of BBP, MBP, and MBzP detected in the worm are within the range detected in human biological samples. Exposure to 10 μM BBP leads to germlines with enlarged mitotic nuclei, altered meiotic progression, activation of a p53/CEP-1-dependent DNA damage checkpoint, increased double-strand break levels throughout the germline, chromosome morphology defects in oocytes at diakinesis, and increased oxidative stress. RNA sequencing analysis indicates that BBP exposure results in the altered expression of genes involved in xenobiotic metabolic processes, extracellular matrix organization, oocyte morphogenesis, meiotic cell cycle, and oxidoreduction. Taken together, we propose that C. elegans exposure to BBP leads to increased oxidative stress and double-strand break formation, thereby compromising germline genomic integrity and chromosome segregation.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 10","pages":"e1011434"},"PeriodicalIF":4.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS GeneticsPub Date : 2024-10-23eCollection Date: 2024-10-01DOI: 10.1371/journal.pgen.1011322
Sheng Fu, William Wheeler, Xiaoyu Wang, Xing Hua, Devika Godbole, Jubao Duan, Bin Zhu, Lu Deng, Fei Qin, Haoyu Zhang, Jianxin Shi, Kai Yu
{"title":"A comprehensive framework for trans-ancestry pathway analysis using GWAS summary data from diverse populations.","authors":"Sheng Fu, William Wheeler, Xiaoyu Wang, Xing Hua, Devika Godbole, Jubao Duan, Bin Zhu, Lu Deng, Fei Qin, Haoyu Zhang, Jianxin Shi, Kai Yu","doi":"10.1371/journal.pgen.1011322","DOIUrl":"10.1371/journal.pgen.1011322","url":null,"abstract":"<p><p>As more multi-ancestry GWAS summary data become available, we have developed a comprehensive trans-ancestry pathway analysis framework that effectively utilizes this diverse genetic information. Within this framework, we evaluated various strategies for integrating genetic data at different levels-SNP, gene, and pathway-from multiple ancestry groups. Through extensive simulation studies, we have identified robust strategies that demonstrate superior performance across diverse scenarios. Applying these methods, we analyzed 6,970 pathways for their association with schizophrenia, incorporating data from African, East Asian, and European populations. Our analysis identified over 200 pathways significantly associated with schizophrenia, even after excluding genes near genome-wide significant loci. This approach substantially enhances detection efficiency compared to traditional single-ancestry pathway analysis and the conventional approach that amalgamates single-ancestry pathway analysis results across different ancestry groups. Our framework provides a flexible and effective tool for leveraging the expanding pool of multi-ancestry GWAS summary data, thereby improving our ability to identify biologically relevant pathways that contribute to disease susceptibility.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 10","pages":"e1011322"},"PeriodicalIF":4.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trajectory-centric framework TrajAtlas reveals multi-scale differentiation heterogeneity among cells, genes, and gene modules in osteogenesis.","authors":"Litian Han, Yaoting Ji, Yiqian Yu, Yueqi Ni, Hao Zeng, Xiaoxin Zhang, Huan Liu, Yufeng Zhang","doi":"10.1371/journal.pgen.1011319","DOIUrl":"10.1371/journal.pgen.1011319","url":null,"abstract":"<p><p>Osteoblasts, the key cells responsible for bone formation and the maintenance of skeletal integrity, originate from a diverse array of progenitor cells. However, the mechanisms underlying osteoblast differentiation from these multiple osteoprogenitors remain poorly understood. To address this knowledge gap, we developed a comprehensive framework to investigate osteoblast differentiation at multiple scales, encompassing cells, genes, and gene modules. We constructed a reference atlas focused on differentiation, which incorporates various osteoprogenitors and provides a seven-level cellular taxonomy. To reconstruct the differentiation process, we developed a model that identifies the transcription factors and pathways involved in differentiation from different osteoprogenitors. Acknowledging that covariates such as age and tissue type can influence differentiation, we created an algorithm to detect differentially expressed genes throughout the differentiation process. Additionally, we implemented methods to identify conserved pseudotemporal gene modules across multiple samples. Overall, our framework systematically addresses the heterogeneity observed during osteoblast differentiation from diverse sources, offering novel insights into the complexities of bone formation and serving as a valuable resource for understanding osteogenesis.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 10","pages":"e1011319"},"PeriodicalIF":4.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS GeneticsPub Date : 2024-10-21eCollection Date: 2024-10-01DOI: 10.1371/journal.pgen.1011441
Grace Biondi, Gina McCormick, Maria P Fernandez
{"title":"The Drosophila circadian clock gene cycle controls the development of clock neurons.","authors":"Grace Biondi, Gina McCormick, Maria P Fernandez","doi":"10.1371/journal.pgen.1011441","DOIUrl":"10.1371/journal.pgen.1011441","url":null,"abstract":"<p><p>Daily behavioral and physiological rhythms are controlled by the brain's circadian timekeeping system, a synchronized network of neurons that maintains endogenous molecular oscillations. These oscillations are based on transcriptional feedback loops of clock genes, which in Drosophila include the transcriptional activators Clock (Clk) and cycle (cyc). While the mechanisms underlying this molecular clock are very well characterized, the roles that the core clock genes play in neuronal physiology and development are much less understood. The Drosophila timekeeping center is composed of ~150 clock neurons, among which the four small ventral lateral neurons (sLNvs) are the most dominant pacemakers under constant conditions. Here, we show that downregulating the clock gene cyc specifically in the Pdf-expressing neurons leads to decreased fasciculation both in larval and adult brains. This effect is due to a developmental role of cyc, as both knocking down cyc or expressing a dominant negative form of cyc exclusively during development lead to defasciculation phenotypes in adult clock neurons. Clk downregulation also leads to developmental effects on sLNv morphology. Our results reveal a non-circadian role for cyc, shedding light on the additional functions of circadian clock genes in the development of the nervous system.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 10","pages":"e1011441"},"PeriodicalIF":4.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS GeneticsPub Date : 2024-10-21eCollection Date: 2024-10-01DOI: 10.1371/journal.pgen.1011447
Jenna E Hountalas, Michael Bunsick, Zhenhua Xu, Andrea A Taylor, Gianni Pescetto, George Ly, François-Didier Boyer, Christopher S P McErlean, Shelley Lumba
{"title":"HTL/KAI2 signaling substitutes for light to control plant germination.","authors":"Jenna E Hountalas, Michael Bunsick, Zhenhua Xu, Andrea A Taylor, Gianni Pescetto, George Ly, François-Didier Boyer, Christopher S P McErlean, Shelley Lumba","doi":"10.1371/journal.pgen.1011447","DOIUrl":"10.1371/journal.pgen.1011447","url":null,"abstract":"<p><p>Plants monitor multiple environmental cues, such as light and temperature, to ensure they germinate at the right time and place. Some specialist plants, like ephemeral fire-following weeds and root parasitic plants, germinate primarily in response to small molecules found in specific environments. Although these species come from distinct clades, they use the same HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE 2 (HTL/KAI2) signaling pathway, to perceive different small molecules suggesting convergent evolution on this pathway. Here, we show that HTL/KAI2 signaling in Arabidopsis thaliana bypasses the light requirement for germination. The HTL/KAI2 downstream component, SUPPRESSOR OF MAX2 1 (SMAX1) accumulates in the dark and is necessary for PHYTOCHROME INTERACTING FACTOR 1/PHYTOCHROME INTERACTING FACTOR 3-LIKE 5 (PIF1/PIL5) to regulate hormone response pathways conducive to germination. The interaction of HTL/KAI2 and light signaling may help to explain how specialist plants like ephemeral and parasitic weeds evolved their germination behaviour in response to specific environments.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 10","pages":"e1011447"},"PeriodicalIF":4.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS GeneticsPub Date : 2024-10-21eCollection Date: 2024-10-01DOI: 10.1371/journal.pgen.1011449
Alena Aliashkevich, Thomas Guest, Laura Alvarez, Michael C Gilmore, Daniel Rea, Jennifer Amstutz, André Mateus, Bastian Schiffthaler, Iñigo Ruiz, Athanasios Typas, Mikhail M Savitski, Pamela J B Brown, Felipe Cava
{"title":"LD-transpeptidation is crucial for fitness and polar growth in Agrobacterium tumefaciens.","authors":"Alena Aliashkevich, Thomas Guest, Laura Alvarez, Michael C Gilmore, Daniel Rea, Jennifer Amstutz, André Mateus, Bastian Schiffthaler, Iñigo Ruiz, Athanasios Typas, Mikhail M Savitski, Pamela J B Brown, Felipe Cava","doi":"10.1371/journal.pgen.1011449","DOIUrl":"10.1371/journal.pgen.1011449","url":null,"abstract":"<p><p>Peptidoglycan (PG), a mesh-like structure which is the primary component of the bacterial cell wall, is crucial to maintain cell integrity and shape. While most bacteria rely on penicillin binding proteins (PBPs) for crosslinking, some species also employ LD-transpeptidases (LDTs). Unlike PBPs, the essentiality and biological functions of LDTs remain largely unclear. The Hyphomicrobiales order of the Alphaproteobacteria, known for their polar growth, have PG which is unusually rich in LD-crosslinks, suggesting that LDTs may play a more significant role in PG synthesis in these bacteria. Here, we investigated LDTs in the plant pathogen Agrobacterium tumefaciens and found that LD-transpeptidation, resulting from at least one of 14 putative LDTs present in this bacterium, is essential for its survival. Notably, a mutant lacking a distinctive group of 7 LDTs which are broadly conserved among the Hyphomicrobiales exhibited reduced LD-crosslinking and tethering of PG to outer membrane β-barrel proteins. Consequently, this mutant suffered severe fitness loss and cell shape rounding, underscoring the critical role played by these Hyphomicrobiales-specific LDTs in maintaining cell wall integrity and promoting elongation. Tn-sequencing screens further revealed non-redundant functions for A. tumefaciens LDTs. Specifically, Hyphomicrobiales-specific LDTs exhibited synthetic genetic interactions with division and cell cycle proteins, and a single LDT from another group. Additionally, our findings demonstrate that strains lacking all LDTs except one displayed distinctive phenotypic profiles and genetic interactions. Collectively, our work emphasizes the critical role of LD-crosslinking in A. tumefaciens cell wall integrity and growth and provides insights into the functional specialization of these crosslinking activities.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"20 10","pages":"e1011449"},"PeriodicalIF":4.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}