C. Spalding, Sandeep Shirgill, E. Taylor, A. Krachler, S. Jabbari
{"title":"铜绿假单胞菌L型的数学模型揭示了宿主防御机制和假定处理之间的复杂相互作用","authors":"C. Spalding, Sandeep Shirgill, E. Taylor, A. Krachler, S. Jabbari","doi":"10.3389/fsysb.2022.899990","DOIUrl":null,"url":null,"abstract":"The bacterium Pseudomonas aeruginosa has been shown to undergo a morphological transition akin to L-forms under exposure to antibiotics, a process which may contribute to persistent infections. With the further consideration of antibiotic-resistance mechanisms, this transition renders the design of effective treatment strategies challenging. Through a mathematical model, we illustrate that additionally incorporating the complexities of the host immune response can render somewhat surprising predictions from the simulations. In particular, scenarios arise whereby the addition of a treatment strategy to directly target the L-forms results in a worsened infection, while in others this treatment could turn an antibiotic-resistant infection from persistent to treatable. The study highlights the importance of understanding the in vivo interplay between immune cells and pathogens for successful treatment design.","PeriodicalId":73109,"journal":{"name":"Frontiers in systems biology","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mathematical Modelling of Pseudomonas aeruginosa L-forms Reveals Complex Interplay Between Host Defence Mechanisms and Putative Treatments\",\"authors\":\"C. Spalding, Sandeep Shirgill, E. Taylor, A. Krachler, S. Jabbari\",\"doi\":\"10.3389/fsysb.2022.899990\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The bacterium Pseudomonas aeruginosa has been shown to undergo a morphological transition akin to L-forms under exposure to antibiotics, a process which may contribute to persistent infections. With the further consideration of antibiotic-resistance mechanisms, this transition renders the design of effective treatment strategies challenging. Through a mathematical model, we illustrate that additionally incorporating the complexities of the host immune response can render somewhat surprising predictions from the simulations. In particular, scenarios arise whereby the addition of a treatment strategy to directly target the L-forms results in a worsened infection, while in others this treatment could turn an antibiotic-resistant infection from persistent to treatable. The study highlights the importance of understanding the in vivo interplay between immune cells and pathogens for successful treatment design.\",\"PeriodicalId\":73109,\"journal\":{\"name\":\"Frontiers in systems biology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-06-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in systems biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3389/fsysb.2022.899990\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in systems biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/fsysb.2022.899990","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Mathematical Modelling of Pseudomonas aeruginosa L-forms Reveals Complex Interplay Between Host Defence Mechanisms and Putative Treatments
The bacterium Pseudomonas aeruginosa has been shown to undergo a morphological transition akin to L-forms under exposure to antibiotics, a process which may contribute to persistent infections. With the further consideration of antibiotic-resistance mechanisms, this transition renders the design of effective treatment strategies challenging. Through a mathematical model, we illustrate that additionally incorporating the complexities of the host immune response can render somewhat surprising predictions from the simulations. In particular, scenarios arise whereby the addition of a treatment strategy to directly target the L-forms results in a worsened infection, while in others this treatment could turn an antibiotic-resistant infection from persistent to treatable. The study highlights the importance of understanding the in vivo interplay between immune cells and pathogens for successful treatment design.