BMC BiologyPub Date : 2024-11-19DOI: 10.1186/s12915-024-02060-3
William T Kay, Paul O'Neill, Sarah J Gurr, Helen N Fones
{"title":"Long-term survival of asexual Zymoseptoria tritici spores in the environment.","authors":"William T Kay, Paul O'Neill, Sarah J Gurr, Helen N Fones","doi":"10.1186/s12915-024-02060-3","DOIUrl":"https://doi.org/10.1186/s12915-024-02060-3","url":null,"abstract":"<p><strong>Background: </strong>The fungal phytopathogen Zymoseptoria tritici, causal agent of the economically damaging Septoria tritici blotch of wheat, is different from most foliar fungal pathogens in that its germination occurs slowly and apparently randomly after arrival on the leaf surface and is followed by a potentially prolonged period of epiphytic growth and even reproduction, during which no feeding structures are formed by the fungus. Thus, understanding the cues for germination and the mechanisms that underpin survival in low-nutrient environments could provide key new avenues for disease control.</p><p><strong>Results: </strong>In this work, we examine survival, culturability and virulence of spores following transfer from a high nutrient environment to water. We find that a sub-population of Z. tritici spores can survive and remain virulent for at least 7 weeks in water alone, during which time multicellular structures split to single cells. The fungus relies heavily on stored lipids; however, if cell suspensions in water are dried, the cells survive without lipid utilisation. Changes in gene expression in the first hours after suspension in water reflect adaptation to stress, while longer term starvation (7 days) induces changes particularly in primary metabolism and cytochrome P450 (CYP) gene expression. Importantly, we also found that Z. tritici spores are equally or better able to survive in soil as in water, and that rain-splash occurring 49 days after soil inoculation can transfer cells to wheat seedlings growing in inoculated soil and cause Septoria leaf blotch disease.</p><p><strong>Conclusions: </strong>Z. tritici blastospores can survive in water or soil for long periods, potentially spanning the intercrop period for UK winter wheat. They rely on internal lipid stores, with no external nutrition, and although a large proportion of spores do not survive for such an extended period, those that do remain as virulent as spores grown on rich media. Thus, Z. tritici has exceptional survival strategies, which are likely to be important in understanding its population genetics and in developing novel routes for Septoria leaf blotch control.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"265"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675273","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}
BMC BiologyPub Date : 2024-11-19DOI: 10.1186/s12915-024-02067-w
Sanan Wu, Xiaoyang Gao, Di Wu, Lu Liu, Han Yao, Xiangjun Meng, Xianglei Zhang, Fang Bai
{"title":"Motif-guided identification of KRAS-interacting proteins.","authors":"Sanan Wu, Xiaoyang Gao, Di Wu, Lu Liu, Han Yao, Xiangjun Meng, Xianglei Zhang, Fang Bai","doi":"10.1186/s12915-024-02067-w","DOIUrl":"https://doi.org/10.1186/s12915-024-02067-w","url":null,"abstract":"<p><strong>Background: </strong>For decades, KRAS has always been a huge challenge to the field of drug discovery for its significance in cancer progression as well as its difficulties in being targeted as an \"undruggable\" protein. KRAS regulates downstream signaling pathways through protein-protein interactions, whereas many interaction partners of KRAS remain unknown.</p><p><strong>Results: </strong>We developed a workflow to computationally predict and experimentally validate the potential KRAS-interacting proteins based on the interaction mode of KRAS and its known binding partners. We extracted 17 KRAS-interacting motifs from all experimentally determined KRAS-containing protein complexes as queries to identify proteins containing fragments structurally similar to the queries in the human protein structure database using our in-house protein-protein interaction prediction method, PPI-Miner. Finally, out of the 78 predicted potential interacting proteins of KRAS, 10 were selected for experimental validation, including BRAF, a previously reported interacting protein, which served as the positive control in our validation experiments. Additionally, a known peptide that binds to KRAS, KRpep-2d, was also used as a positive control. The predicted interacting motifs of these 10 proteins were synthesized to perform biolayer interferometry assays, with 4 out of 10 exhibiting binding affinities to KRAS, and the strongest, GRB10, was selected for further validation. Additionally, the interaction between GRB10 (RA-PH domain) and KRAS was confirmed via immunofluorescence and co-immunoprecipitation.</p><p><strong>Conclusions: </strong>These results demonstrate the effectiveness of our workflow in predicting potential interacting proteins for KRAS and deepen the understanding of KRAS-driven tumor mechanisms and the development of therapeutic strategies.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"264"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675246","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}
BMC BiologyPub Date : 2024-11-18DOI: 10.1186/s12915-024-02065-y
Paula Ávila-Fernández, Miguel Etayo-Escanilla, David Sánchez-Porras, Ricardo Fernández-Valadés, Fernando Campos, Ingrid Garzón, Víctor Carriel, Miguel Alaminos, Óscar Darío García-García, Jesús Chato-Astrain
{"title":"Spatiotemporal characterization of extracellular matrix maturation in human artificial stromal-epithelial tissue substitutes.","authors":"Paula Ávila-Fernández, Miguel Etayo-Escanilla, David Sánchez-Porras, Ricardo Fernández-Valadés, Fernando Campos, Ingrid Garzón, Víctor Carriel, Miguel Alaminos, Óscar Darío García-García, Jesús Chato-Astrain","doi":"10.1186/s12915-024-02065-y","DOIUrl":"10.1186/s12915-024-02065-y","url":null,"abstract":"<p><strong>Background: </strong>Tissue engineering techniques offer new strategies to understand complex processes in a controlled and reproducible system. In this study, we generated bilayered human tissue substitutes consisting of a cellular connective tissue with a suprajacent epithelium (full-thickness stromal-epithelial substitutes or SESS) and human tissue substitutes with an epithelial layer generated on top of an acellular biomaterial (epithelial substitutes or ESS). Both types of artificial tissues were studied at sequential time periods to analyze the maturation process of the extracellular matrix.</p><p><strong>Results: </strong>Regarding epithelial layer, ESS cells showed active proliferation, positive expression of cytokeratin 5, and low expression of differentiation markers, whereas SESS epithelium showed higher differentiation levels, with a progressive positive expression of cytokeratin 10 and claudin. Stromal cells in SESS tended to accumulate and actively synthetize extracellular matrix components such as collagens and proteoglycans in the stromal area in direct contact with the epithelium (zone 1), whereas these components were very scarce in ESS. Regarding the basement membrane, ESS showed a partially differentiated structure containing fibronectin-1 and perlecan. However, SESS showed higher basement membrane differentiation, with positive expression of fibronectin 1, perlecan, nidogen 1, chondroitin-6-sulfate proteoglycans, agrin, and collagens types IV and VII, although this structure was negative for lumican. Finally, both ESS and SESS proved to be useful tools for studying metabolic pathway regulation, revealing differential activation and upregulation of the transforming growth factor-β pathway in ESS and SESS.</p><p><strong>Conclusions: </strong>These results confirm the relevance of epithelial-stromal interaction for extracellular matrix development and differentiation, especially regarding basement membrane components, and suggest the usefulness of bilayered artificial tissue substitutes to reproduce ex vivo the extracellular matrix maturation and development process of human tissues.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"263"},"PeriodicalIF":4.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667365","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}
BMC BiologyPub Date : 2024-11-15DOI: 10.1186/s12915-024-02062-1
Shaoyu Zhong, Lu Zheng, Yi Wu, Shujin Sun, Qing Luo, Guanbin Song, Dongyuan Lü, Mian Long
{"title":"Rotating culture regulates the formation of HepaRG-derived liver organoids via YAP translocation.","authors":"Shaoyu Zhong, Lu Zheng, Yi Wu, Shujin Sun, Qing Luo, Guanbin Song, Dongyuan Lü, Mian Long","doi":"10.1186/s12915-024-02062-1","DOIUrl":"10.1186/s12915-024-02062-1","url":null,"abstract":"<p><strong>Background: </strong>Liver organoid serves as an alternative model for liver pathophysiology in carbohydrate or lipid metabolism and xenobiotic metabolism transformation. Biomechanical cues including spaceflight mission can affect liver organoid construction and their related functions, but their underlying mechanisms are not fully understood yet. Here, a rotating cell culture device, namely Rotating Flat Chamber (RFC), was specifically designed for adhering cells or cell aggregated to elucidate the effects of altered gravity vector on HepaRG-derived liver organoids construction.</p><p><strong>Results: </strong>The organoids so formed under RFC presented the fast growth rate and large projection area. Meanwhile, the expressions of two pluripotency markers of SOX9 and CD44 were enhanced. This finding was positively correlated with the increased YAP expression and nuclear translocation as well as the elevated α<sub>4</sub>β<sub>6</sub>-integrin expression. Inhibition of YAP expression and nuclear translocation decreased the expression of SOX9 and CD44 under RFC, thereby attenuating the pluripotency of HepaRG-derived liver organoids.</p><p><strong>Conclusions: </strong>In conclusion, we proposed a novel liver organoid construction method using rotating culture, by which the pluripotency of liver organoids so constructed is mediated by α<sub>4</sub>β<sub>6</sub>-integrin and YAP translocation. This work furthered the understanding in how the gravity vector orientation affects the construction of liver organoids and the related mechanotransductive pathways.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"262"},"PeriodicalIF":4.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643434","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}
BMC BiologyPub Date : 2024-11-15DOI: 10.1186/s12915-024-02063-0
Antoinette J Piaggio, Luke Gierus, Daniel R Taylor, Nick D Holmes, David J Will, Neil J Gemmell, Paul Q Thomas
{"title":"Building an eDNA surveillance toolkit for invasive rodents on islands: can we detect wild-type and gene drive Mus musculus?","authors":"Antoinette J Piaggio, Luke Gierus, Daniel R Taylor, Nick D Holmes, David J Will, Neil J Gemmell, Paul Q Thomas","doi":"10.1186/s12915-024-02063-0","DOIUrl":"10.1186/s12915-024-02063-0","url":null,"abstract":"<p><strong>Background: </strong>Invasive management strategies range from preventing new invasive species incursions to eliminating established populations, with all requiring effective monitoring to guide action. The use of DNA sampled from the environment (eDNA) is one such tool that provides the ability to surveille and monitor target invasive species through passive sampling. Technology being developed to eliminate invasive species includes genetic biocontrol in the form of gene drive. This approach would drive a trait through a population and could be used to eliminate or modify a target population. Once a gene drive organism is released into a population then monitoring changes in density of the target species and the spread of the drive in the population would be critical.</p><p><strong>Results: </strong>In this paper, we use invasive Mus musculus as a model for development of an eDNA assay that detects wild-type M. musculus and gene drive M. musculus. We demonstrate successful development of an assay where environmental samples could be used to detect wild-type invasive M. musculus and the relative density of wild-type to gene drive M. musculus.</p><p><strong>Conclusions: </strong>The development of a method that detects both wild-type M. musculus and a gene drive M. musculus (t<sub>CRISPR</sub>) from environmental samples expands the utility of environmental DNA. This method provides a tool that can immediately be deployed for invasive wild M. musculus management across the world. This is a proof-of-concept that a genetic biocontrol construct could be monitored using environmental samples.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"261"},"PeriodicalIF":4.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643398","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}
BMC BiologyPub Date : 2024-11-14DOI: 10.1186/s12915-024-02058-x
Kui Wang, Tian-Lun Chen, Xin-Xin Zhang, Jian-Bin Cao, Pengcheng Wang, Mingcang Wang, Jiu-Lin Du, Yu Mu, Rongkun Tao
{"title":"Unveiling tryptophan dynamics and functions across model organisms via quantitative imaging.","authors":"Kui Wang, Tian-Lun Chen, Xin-Xin Zhang, Jian-Bin Cao, Pengcheng Wang, Mingcang Wang, Jiu-Lin Du, Yu Mu, Rongkun Tao","doi":"10.1186/s12915-024-02058-x","DOIUrl":"10.1186/s12915-024-02058-x","url":null,"abstract":"<p><strong>Background: </strong>Tryptophan is an essential amino acid involved in critical cellular processes in vertebrates, serving as a precursor for serotonin and kynurenine, which are key neuromodulators to influence neural and immune functions. Systematic and quantitative measurement of tryptophan is vital to understanding these processes.</p><p><strong>Results: </strong>Here, we utilized a robust and highly responsive green ratiometric indicator for tryptophan (GRIT) to quantitatively measure tryptophan dynamics in bacteria, mitochondria of mammalian cell cultures, human serum, and intact zebrafish. At the cellular scale, these quantitative analyses uncovered differences in tryptophan dynamics across cell types and organelles. At the whole-organism scale, we revealed that inflammation-induced tryptophan concentration increases in zebrafish brain led to elevated serotonin and kynurenine levels, prolonged sleep duration, suggesting a novel metabolic connection between immune response and behavior. Moreover, GRIT's application in detecting reduced serum tryptophan levels in patients with inflammation symptoms suggests its potential as a high-throughput diagnostic tool.</p><p><strong>Conclusions: </strong>In summary, this study introduces GRIT as a powerful method for studying tryptophan metabolism and its broader physiological implications, paving the way for new insights into the metabolic regulation of health and disease across multiple biological scales.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"258"},"PeriodicalIF":4.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615265","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}
BMC BiologyPub Date : 2024-11-14DOI: 10.1186/s12915-024-02038-1
Richard J McDowell, Altug Didikoglu, Tom Woelders, Mazie J Gatt, Finn Moffatt, Saba Notash, Roelof A Hut, Timothy M Brown, Robert J Lucas
{"title":"Beyond Lux: methods for species and photoreceptor-specific quantification of ambient light for mammals.","authors":"Richard J McDowell, Altug Didikoglu, Tom Woelders, Mazie J Gatt, Finn Moffatt, Saba Notash, Roelof A Hut, Timothy M Brown, Robert J Lucas","doi":"10.1186/s12915-024-02038-1","DOIUrl":"10.1186/s12915-024-02038-1","url":null,"abstract":"<p><strong>Background: </strong>Light is a key environmental regulator of physiology and behaviour. Mistimed or insufficient light disrupts circadian rhythms and is associated with impaired health and well-being across mammals. Appropriate lighting is therefore crucial for indoor housed mammals. Light is commonly measured in lux. However, this employs a spectral weighting function for human luminance and is not suitable for 'non-visual' effects of light or use across species. In humans, a photoreceptor-specific (α-opic) metrology system has been proposed as a more appropriate way of measuring light.</p><p><strong>Results: </strong>Here we establish technology to allow this α-opic measurement approach to be readily extended across mammalian species, accounting for differences in photoreceptor types, photopigment spectral sensitivities, and eye anatomy. We develop a high-throughput method to derive spectral sensitivities for recombinantly expressed mammalian opsins and use it to establish the spectral sensitivity of melanopsin from 13 non-human mammals. We further address the need for simple measurement strategies for species-specific α-opic measures by developing an accessible online toolbox for calculating these units and validating an open hardware multichannel light sensor for 'point and click' measurement. We finally demonstrate that species-specific α-opic measurements are superior to photopic lux as predictors of physiological responses to light in mice and allow ecologically relevant comparisons of photosensitivity between species.</p><p><strong>Conclusions: </strong>Our study presents methods for measuring light in species-specific α-opic units that are superior to the existing unit of photopic lux and holds the promise of improvements to the health and welfare of animals, scientific research reproducibility, agricultural productivity, and energy usage.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"257"},"PeriodicalIF":4.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615249","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}
BMC BiologyPub Date : 2024-11-14DOI: 10.1186/s12915-024-02064-z
Jing Li, Shida He, Jian Zhang, Feng Zhang, Quan Zou, Fengming Ni
{"title":"T4Seeker: a hybrid model for type IV secretion effectors identification.","authors":"Jing Li, Shida He, Jian Zhang, Feng Zhang, Quan Zou, Fengming Ni","doi":"10.1186/s12915-024-02064-z","DOIUrl":"10.1186/s12915-024-02064-z","url":null,"abstract":"<p><strong>Background: </strong>The type IV secretion system is widely present in various bacteria, such as Salmonella, Escherichia coli, and Helicobacter pylori. These bacteria use the type IV secretion system to secrete type IV secretion effectors, infect host cells, and disrupt or modulate the communication pathways. In this study, type III and type VI secretion effectors were used as negative samples to train a robust model.</p><p><strong>Results: </strong>The area under the curve of T4Seeker on the validation and independent test sets were 0.947 and 0.970, respectively, demonstrating the strong predictive capacity and robustness of T4Seeker. After comparing with the classic and state-of-the-art T4SE identification models, we found that T4Seeker, which is based on traditional features and large language model features, had a higher predictive ability.</p><p><strong>Conclusion: </strong>The T4Seeker proposed in this study demonstrates superior performance in the field of T4SEs prediction. By integrating features at multiple levels, it achieves higher predictive accuracy and strong generalization capability, providing an effective tool for future T4SE research.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"259"},"PeriodicalIF":4.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615255","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}
BMC BiologyPub Date : 2024-11-14DOI: 10.1186/s12915-024-02055-0
Chao Cao, Chunyu Wang, Qi Dai, Quan Zou, Tao Wang
{"title":"CRBPSA: CircRNA-RBP interaction sites identification using sequence structural attention model.","authors":"Chao Cao, Chunyu Wang, Qi Dai, Quan Zou, Tao Wang","doi":"10.1186/s12915-024-02055-0","DOIUrl":"10.1186/s12915-024-02055-0","url":null,"abstract":"<p><strong>Background: </strong>Due to the ability of circRNA to bind with corresponding RBPs and play a critical role in gene regulation and disease prevention, numerous identification algorithms have been developed. Nevertheless, most of the current mainstream methods primarily capture one-dimensional sequence features through various descriptors, while neglecting the effective extraction of secondary structure features. Moreover, as the number of introduced descriptors increases, the issues of sparsity and ineffective representation also rise, causing a significant burden on computational models and leaving room for improvement in predictive performance.</p><p><strong>Results: </strong>Based on this, we focused on capturing the features of secondary structure in sequences and developed a new architecture called CRBPSA, which is based on a sequence-structure attention mechanism. Firstly, a base-pairing matrix is generated by calculating the matching probability between each base, with a Gaussian function introduced as a weight to construct the secondary structure. Then, a Structure_Transformer is employed to extract base-pairing information and spatial positional dependencies, enabling the identification of binding sites through deeper feature extraction. Experimental results using the same set of hyperparameters on 37 circRNA datasets, totaling 671,952 samples, show that the CRBPSA algorithm achieves an average AUC of 99.93%, surpassing all existing prediction methods.</p><p><strong>Conclusions: </strong>CRBPSA is a lightweight and efficient prediction tool for circRNA-RBP, which can capture structural features of sequences with minimal computational resources and accurately predict protein-binding sites. This tool facilitates a deeper understanding of the biological processes and mechanisms underlying circRNA and protein interactions.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"260"},"PeriodicalIF":4.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615252","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}
BMC BiologyPub Date : 2024-11-11DOI: 10.1186/s12915-024-02056-z
Narendra K Dewangan, Sayed Golam Mohiuddin, Shayne Sensenbach, Prashant Karki, Mehmet A Orman
{"title":"Uncovering bacterial-mammalian cell interactions via single-cell tracking.","authors":"Narendra K Dewangan, Sayed Golam Mohiuddin, Shayne Sensenbach, Prashant Karki, Mehmet A Orman","doi":"10.1186/s12915-024-02056-z","DOIUrl":"10.1186/s12915-024-02056-z","url":null,"abstract":"<p><strong>Background: </strong>The interactions between bacterial pathogens and host cells are characterized by a multitude of complexities, leading to a wide range of heterogeneous outcomes. Despite extensive research, we still have a limited understanding of how bacterial motility in complex environments impacts their ability to tolerate antibiotics and adhere to mammalian cell surfaces. The challenge lies in unraveling the complexity of these interactions and developing quantitative microscopy approaches to predict the behavior of bacterial populations.</p><p><strong>Results: </strong>To address this challenge, we directed our efforts towards Pseudomonas aeruginosa, a pathogenic bacterium known for producing thick films in the lungs of cystic fibrosis patients, and Escherichia coli, used as a proof of concept to develop and demonstrate our single-cell tracking approaches. Our results revealed that P. aeruginosa exhibits diverse and complex interactions on mammalian cell surfaces, such as adhesion, rotational motion, and swimming, unlike the less interactive behavior of Escherichia coli. Our analysis indicated that P. aeruginosa demonstrated lower mean-squared displacement (MSD) values and greater adherence to mammalian cells compared to E. coli, which showed higher MSD slopes and less frequent adherence. Genetic mutations in membrane proteins of P. aeruginosa resulted in altered displacement patterns and reduced adhesion, with the ΔfliD mutant displaying a more Gaussian displacement distribution and significantly less adherence to mammalian cells. Adhesion and tolerance mechanisms are diverse and complex, potentially involving distinct pathways; however, our findings highlight the therapeutic potential of targeting the fliD gene (encoding a critical flagellum protein), as its deletion not only reduced adherence but also antibiotic tolerance.</p><p><strong>Conclusions: </strong>Overall, our findings underscore the importance of single cell tracking in accurately assessing bacterial behavior over short time periods and highlight its significant potential in guiding effective intervention strategies.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"22 1","pages":"256"},"PeriodicalIF":4.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615259","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}