PLoS Biology最新文献_第6页

The human posterior parietal cortices orthogonalize the representation of different streams of information concurrently coded in visual working memory. 人类的后顶叶皮层将视觉工作记忆中同时编码的不同信息流正交化。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-11-21 eCollection Date: 2024-11-01 DOI: 10.1371/journal.pbio.3002915

Yaoda Xu

{"title":"The human posterior parietal cortices orthogonalize the representation of different streams of information concurrently coded in visual working memory.","authors":"Yaoda Xu","doi":"10.1371/journal.pbio.3002915","DOIUrl":"10.1371/journal.pbio.3002915","url":null,"abstract":"The key to adaptive visual processing lies in the ability to maintain goal-directed visual representation in the face of distraction. In visual working memory (VWM), distraction may come from the coding of distractors or other concurrently retained targets. This fMRI study reveals a common representational geometry that our brain uses to combat both types of distractions in VWM. Specifically, using fMRI pattern decoding, the human posterior parietal cortex is shown to orthogonalize the representations of different streams of information concurrently coded in VWM, whether they are targets and distractors, or different targets concurrently held in VWM. The latter is also seen in the human occipitotemporal cortex. Such a representational geometry provides an elegant and simple solution to enable independent information readout, effectively combating distraction from the different streams of information, while accommodating their concurrent representations. This representational scheme differs from mechanisms that actively suppress or block the encoding of distractors to reduce interference. It is likely a general neural representational principle that supports our ability to represent information beyond VWM in other situations where multiple streams of visual information are tracked and processed simultaneously.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002915"},"PeriodicalIF":9.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689364","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}

引用次数: 0

Stochastic models allow improved inference of microbiome interactions from time series data. 通过随机模型，可以更好地从时间序列数据中推断微生物组的相互作用。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-11-21 eCollection Date: 2024-11-01 DOI: 10.1371/journal.pbio.3002913

Román Zapién-Campos, Florence Bansept, Arne Traulsen

{"title":"Stochastic models allow improved inference of microbiome interactions from time series data.","authors":"Román Zapién-Campos, Florence Bansept, Arne Traulsen","doi":"10.1371/journal.pbio.3002913","DOIUrl":"10.1371/journal.pbio.3002913","url":null,"abstract":"How can we figure out how the different microbes interact within microbiomes? To combine theoretical models and experimental data, we often fit a deterministic model for the mean dynamics of a system to averaged data. However, in the averaging procedure a lot of information from the data is lost-and a deterministic model may be a poor representation of a stochastic reality. Here, we develop an inference method for microbiomes based on the idea that both the experiment and the model are stochastic. Starting from a stochastic model, we derive dynamical equations not only for the average, but also for higher statistical moments of the microbial abundances. We use these equations to infer distributions of the interaction parameters that best describe the biological experimental data-improving identifiability and precision. The inferred distributions allow us to make predictions but also to distinguish between fairly certain parameters and those for which the available experimental data does not give sufficient information. Compared to related approaches, we derive expressions that also work for the relative abundance of microbes, enabling us to use conventional metagenome data, and account for cases where not a single host, but only replicate hosts, can be tracked over time.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002913"},"PeriodicalIF":9.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689362","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}

引用次数: 0

Turnover of retroelements and satellite DNA drives centromere reorganization over short evolutionary timescales in Drosophila. 在果蝇的短进化时间尺度内，逆转录素和卫星 DNA 的交替推动了中心粒的重组。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-11-21 eCollection Date: 2024-11-01 DOI: 10.1371/journal.pbio.3002911

Cécile Courret, Lucas W Hemmer, Xiaolu Wei, Prachi D Patel, Bryce J Chabot, Nicholas J Fuda, Xuewen Geng, Ching-Ho Chang, Barbara G Mellone, Amanda M Larracuente

{"title":"Turnover of retroelements and satellite DNA drives centromere reorganization over short evolutionary timescales in Drosophila.","authors":"Cécile Courret, Lucas W Hemmer, Xiaolu Wei, Prachi D Patel, Bryce J Chabot, Nicholas J Fuda, Xuewen Geng, Ching-Ho Chang, Barbara G Mellone, Amanda M Larracuente","doi":"10.1371/journal.pbio.3002911","DOIUrl":"10.1371/journal.pbio.3002911","url":null,"abstract":"Centromeres reside in rapidly evolving, repeat-rich genomic regions, despite their essential function in chromosome segregation. Across organisms, centromeres are rich in selfish genetic elements such as transposable elements and satellite DNAs that can bias their transmission through meiosis. However, these elements still need to cooperate at some level and contribute to, or avoid interfering with, centromere function. To gain insight into the balance between conflict and cooperation at centromeric DNA, we take advantage of the close evolutionary relationships within the Drosophila simulans clade-D. simulans, D. sechellia, and D. mauritiana-and their relative, D. melanogaster. Using chromatin profiling combined with high-resolution fluorescence in situ hybridization on stretched chromatin fibers, we characterize all centromeres across these species. We discovered dramatic centromere reorganization involving recurrent shifts between retroelements and satellite DNAs over short evolutionary timescales. We also reveal the recent origin (<240 Kya) of telocentric chromosomes in D. sechellia, where the X and fourth centromeres now sit on telomere-specific retroelements. Finally, the Y chromosome centromeres, which are the only chromosomes that do not experience female meiosis, do not show dynamic cycling between satDNA and TEs. The patterns of rapid centromere turnover in these species are consistent with genetic conflicts in the female germline and have implications for centromeric DNA function and karyotype evolution. Regardless of the evolutionary forces driving this turnover, the rapid reorganization of centromeric sequences over short evolutionary timescales highlights their potential as hotspots for evolutionary innovation.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002911"},"PeriodicalIF":9.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689368","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}

引用次数: 0

Thalamic spindles and Up states coordinate cortical and hippocampal co-ripples in humans. 丘脑纺锤体和上升状态协调人类皮层和海马的共同损伤。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-11-19 eCollection Date: 2024-11-01 DOI: 10.1371/journal.pbio.3002855

Charles W Dickey, Ilya A Verzhbinsky, Sophie Kajfez, Burke Q Rosen, Christopher E Gonzalez, Patrick Y Chauvel, Sydney S Cash, Sandipan Pati, Eric Halgren

{"title":"Thalamic spindles and Up states coordinate cortical and hippocampal co-ripples in humans.","authors":"Charles W Dickey, Ilya A Verzhbinsky, Sophie Kajfez, Burke Q Rosen, Christopher E Gonzalez, Patrick Y Chauvel, Sydney S Cash, Sandipan Pati, Eric Halgren","doi":"10.1371/journal.pbio.3002855","DOIUrl":"10.1371/journal.pbio.3002855","url":null,"abstract":"In the neocortex, ~90 Hz ripples couple to ~12 Hz sleep spindles on the ~1 Hz Down-to-Up state transition during non-rapid eye movement sleep. This conjunction of sleep waves is critical for the consolidation of memories into long-term storage. The widespread co-occurrences of ripples (\"co-ripples\") may integrate information across the neocortex and hippocampus to facilitate consolidation. While the thalamus synchronizes spindles and Up states in the cortex for memory, it is not known whether it may also organize co-ripples. Using human intracranial recordings during NREM sleep, we investigated whether cortico-cortical co-ripples and hippocampo-cortical co-ripples are either: (1) driven by directly projected thalamic ripples; or (2) coordinated by propagating thalamic spindles or Up states. We found ripples in the anterior and posterior thalamus, with similar characteristics as hippocampal and cortical ripples, including having a center frequency of ~90 Hz and coupling to local spindles on the Down-to-Up state transition. However, thalamic ripples rarely co-occur or phase-lock with cortical or hippocampal ripples. By contrast, spindles and Up states that propagate from the thalamus strongly coordinate co-ripples in the cortex and hippocampus. Thus, thalamo-cortical spindles and Up states, rather than thalamic ripples, may provide input facilitating spatially distributed co-rippling that integrates information for memory consolidation during sleep in humans.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002855"},"PeriodicalIF":9.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677383","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}

引用次数: 0

Correction: Dog-human vocal interactions match dogs' sensory-motor tuning. 更正：狗与人之间的声音互动与狗的感觉运动调谐相匹配。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-11-19 eCollection Date: 2024-11-01 DOI: 10.1371/journal.pbio.3002923

Eloïse C Déaux, Théophane Piette, Florence Gaunet, Thierry Legou, Luc Arnal, Anne-Lise Giraud

引用次数: 0

Trajectories of human brain functional connectome maturation across the birth transition. 跨越出生过渡期的人脑功能连接组成熟轨迹。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-11-19 eCollection Date: 2024-11-01 DOI: 10.1371/journal.pbio.3002909

Lanxin Ji, Iris Menu, Amyn Majbri, Tanya Bhatia, Christopher J Trentacosta, Moriah E Thomason

{"title":"Trajectories of human brain functional connectome maturation across the birth transition.","authors":"Lanxin Ji, Iris Menu, Amyn Majbri, Tanya Bhatia, Christopher J Trentacosta, Moriah E Thomason","doi":"10.1371/journal.pbio.3002909","DOIUrl":"10.1371/journal.pbio.3002909","url":null,"abstract":"Understanding the sequence and timing of brain functional network development at the beginning of human life is critically important from both normative and clinical perspectives. Yet, we presently lack rigorous examination of the longitudinal emergence of human brain functional networks over the birth transition. Leveraging a large, longitudinal perinatal functional magnetic resonance imaging (fMRI) data set, this study models developmental trajectories of brain functional networks spanning 25 to 55 weeks of post-conceptual gestational age (GA). The final sample includes 126 fetal scans (GA = 31.36 ± 3.83 weeks) and 58 infant scans (GA = 48.17 ± 3.73 weeks) from 140 unique subjects. In this study, we document the developmental changes of resting-state functional connectivity (RSFC) over the birth transition, evident at both network and graph levels. We observe that growth patterns are regionally specific, with some areas showing minimal RSFC changes, while others exhibit a dramatic increase at birth. Examples with birth-triggered dramatic change include RSFC within the subcortical network, within the superior frontal network, within the occipital-cerebellum joint network, as well as the cross-hemisphere RSFC between the bilateral sensorimotor networks and between the bilateral temporal network. Our graph analysis further emphasized the subcortical network as the only region of the brain exhibiting a significant increase in local efficiency around birth, while a concomitant gradual increase was found in global efficiency in sensorimotor and parietal-frontal regions throughout the fetal to neonatal period. This work unveils fundamental aspects of early brain development and lays the foundation for future work on the influence of environmental factors on this process.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002909"},"PeriodicalIF":9.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677389","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}

引用次数: 0

Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. 突触前 cAMP-PKA 介导的电位诱导海马苔藓纤维突触小泡池及通道-小泡耦合的重新配置。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-11-18 eCollection Date: 2024-11-01 DOI: 10.1371/journal.pbio.3002879

Olena Kim, Yuji Okamoto, Walter A Kaufmann, Nils Brose, Ryuichi Shigemoto, Peter Jonas

{"title":"Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons.","authors":"Olena Kim, Yuji Okamoto, Walter A Kaufmann, Nils Brose, Ryuichi Shigemoto, Peter Jonas","doi":"10.1371/journal.pbio.3002879","DOIUrl":"10.1371/journal.pbio.3002879","url":null,"abstract":"It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy (EM) and freeze-fracture replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic transmission revealed that forskolin-induced chemical potentiation increased the readily releasable vesicle pool size and vesicular release probability by 146% and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL demonstrated an increase in the number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1, indicating an increase in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones. We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002879"},"PeriodicalIF":9.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669300","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}

引用次数: 0

Excess mortality of infected ectotherms induced by warming depends on pathogen kingdom and evolutionary history. 气候变暖导致受感染的外温动物死亡率过高，这取决于病原体的种类和进化历史。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-11-18 eCollection Date: 2024-11-01 DOI: 10.1371/journal.pbio.3002900

Jingdi Li, Nele Guttmann, Georgia C Drew, Tobias E Hector, Justyna Wolinska, Kayla C King

{"title":"Excess mortality of infected ectotherms induced by warming depends on pathogen kingdom and evolutionary history.","authors":"Jingdi Li, Nele Guttmann, Georgia C Drew, Tobias E Hector, Justyna Wolinska, Kayla C King","doi":"10.1371/journal.pbio.3002900","DOIUrl":"10.1371/journal.pbio.3002900","url":null,"abstract":"Climate change is causing extreme heating events and can lead to more infectious disease outbreaks, putting species persistence at risk. The extent to which warming temperatures and infection may together impair host health is unclear. Using a meta-analysis of >190 effect sizes representing 101 ectothermic animal host-pathogen systems, we demonstrate that warming significantly increased the mortality of hosts infected by bacterial pathogens. Pathogens that have been evolutionarily established within the host species showed higher virulence under warmer temperatures. Conversely, the effect of warming on novel infections-from pathogens without a shared evolutionary history with the host species-were more pronounced with larger differences between compared temperatures. We found that compared to established infections, novel infections were more deadly at lower/baseline temperatures. Moreover, we revealed that the virulence of fungal pathogens increased only when temperatures were shifted upwards towards the pathogen thermal optimum. The magnitude of all these significant effects was not impacted by host life-stage, immune complexity, pathogen inoculation methods, or exposure time. Overall, our findings reveal distinct patterns in changes of pathogen virulence during warming. We highlight the importance of pathogen taxa, thermal optima, and evolutionary history in determining the impact of global change on infection outcomes.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002900"},"PeriodicalIF":9.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669285","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}

引用次数: 0

Dopamine neurons that inform Drosophila olfactory memory have distinct, acute functions driving attraction and aversion. 为果蝇嗅觉记忆提供信息的多巴胺神经元具有驱动吸引和厌恶的不同的急性功能。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-11-18 eCollection Date: 2024-11-01 DOI: 10.1371/journal.pbio.3002843

Farhan Mohammad, Yishan Mai, Joses Ho, Xianyuan Zhang, Stanislav Ott, James Charles Stewart, Adam Claridge-Chang

{"title":"Dopamine neurons that inform Drosophila olfactory memory have distinct, acute functions driving attraction and aversion.","authors":"Farhan Mohammad, Yishan Mai, Joses Ho, Xianyuan Zhang, Stanislav Ott, James Charles Stewart, Adam Claridge-Chang","doi":"10.1371/journal.pbio.3002843","DOIUrl":"10.1371/journal.pbio.3002843","url":null,"abstract":"The brain must guide immediate responses to beneficial and harmful stimuli while simultaneously writing memories for future reference. While both immediate actions and reinforcement learning are instructed by dopamine, how dopaminergic systems maintain coherence between these 2 reward functions is unknown. Through optogenetic activation experiments, we showed that the dopamine neurons that inform olfactory memory in Drosophila have a distinct, parallel function driving attraction and aversion (valence). Sensory neurons required for olfactory memory were dispensable to dopaminergic valence. A broadly projecting set of dopaminergic cells had valence that was dependent on dopamine, glutamate, and octopamine. Similarly, a more restricted dopaminergic cluster with attractive valence was reliant on dopamine and glutamate; flies avoided opto-inhibition of this narrow subset, indicating the role of this cluster in controlling ongoing behavior. Dopamine valence was distinct from output-neuron opto-valence in locomotor pattern, strength, and polarity. Overall, our data suggest that dopamine's acute effect on valence provides a mechanism by which a dopaminergic system can coherently write memories to influence future responses while guiding immediate attraction and aversion.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002843"},"PeriodicalIF":9.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669282","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}

引用次数: 0

Niche-specific metabolic phenotypes can be used to identify antimicrobial targets in pathogens. 利基特异性代谢表型可用于确定病原体的抗菌靶标。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-11-18 eCollection Date: 2024-11-01 DOI: 10.1371/journal.pbio.3002907

Emma M Glass, Lillian R Dillard, Glynis L Kolling, Andrew S Warren, Jason A Papin

{"title":"Niche-specific metabolic phenotypes can be used to identify antimicrobial targets in pathogens.","authors":"Emma M Glass, Lillian R Dillard, Glynis L Kolling, Andrew S Warren, Jason A Papin","doi":"10.1371/journal.pbio.3002907","DOIUrl":"10.1371/journal.pbio.3002907","url":null,"abstract":"Bacterial pathogens pose a major risk to human health, leading to tens of millions of deaths annually and significant global economic losses. While bacterial infections are typically treated with antibiotic regimens, there has been a rapid emergence of antimicrobial resistant (AMR) bacterial strains due to antibiotic overuse. Because of this, treatment of infections with traditional antimicrobials has become increasingly difficult, necessitating the development of innovative approaches for deeply understanding pathogen function. To combat issues presented by broad- spectrum antibiotics, the idea of narrow-spectrum antibiotics has been previously proposed and explored. Rather than interrupting universal bacterial cellular processes, narrow-spectrum antibiotics work by targeting specific functions or essential genes in certain species or subgroups of bacteria. Here, we generate a collection of genome-scale metabolic network reconstructions (GENREs) of pathogens through an automated computational pipeline. We used these GENREs to identify subgroups of pathogens that share unique metabolic phenotypes and determined that pathogen physiological niche plays a role in the development of unique metabolic function. For example, we identified several unique metabolic phenotypes specific to stomach pathogens. We identified essential genes unique to stomach pathogens in silico and a corresponding inhibitory compound for a uniquely essential gene. We then validated our in silico predictions with an in vitro microbial growth assay. We demonstrated that the inhibition of a uniquely essential gene, thyX, inhibited growth of stomach-specific pathogens exclusively, indicating possible physiological location-specific targeting. This pioneering computational approach could lead to the identification of unique metabolic signatures to inform future targeted, physiological location-specific, antimicrobial therapies, reducing the need for broad-spectrum antibiotics.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002907"},"PeriodicalIF":9.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669289","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}

引用次数: 0