Analysing the integrated quorum sensing system its potential role in Pseudomonas aeruginosa pathogenesis

Juan Raya^*

• Spanish National Research Council (CSIC), Madrid, Spain

Barcelona, 24th of March, 2025 Dear Editor, Please find the revised version of the paper by Raya et al entitled Analysing the integrated quorum sensing (Iqs) system and its potential role in Pseudomonas aeruginosa pathogenesis. We have followed all the reviewer suggestions, which I think have significantly contributed to increase the quality of the paper. We hope that the present version will suitable for publication in Frontiers in Cellular and Infection Microbiology.The manuscript entitled "Analyzing the Integrated Quorum Sensing (Iqs) System and Its Potential Role in Pseudomonas aeruginosa Pathogenesis" discusses the fourth IQS system and highlights how it controls the hierarchy of quorum sensing in Pseudomonas aeruginosa. The authors did a great job comprehensively detailing the IQS, and I liked the way they connected it with the ambantimetabolite in Pseudomonas aeruginosa and its correlation with pyochelin. They discussed how it is synthesized as a byproduct of the pyochelin synthesis pathway, dihydroaerugionic acid, and how it converts to IQS through a simple dehydrating step. They also highlighted compound B11, which has shown promising results in the initial screening as a QS inhibitor, reducing the pathogenicity of Pseudomonas aeruginosa by inhibiting various virulence factors. Overall, it is a very good review of IQS, focusing on every detail, from its synthesis to its role in regulation and applicationIn the Review manuscript "Analysing the integrated quorum sensing (Iqs) system and its 6 potential role in Pseudomonas aeruginosa pathogenesis" the authors have discussed the discovery and role of IQS system in P. aeruginosa. The article is well written. However, I have encountered some minor errors that need to be responded to and some details need to be added. AbstractLine 40-"survival mechanisms" ….of whom complete the sentence IntroductionWe would like thank the reviewer for noticing this error. In the present version, the sentence has been completed.2. Either add more details about the pathogenicity of P. aeruginosa in the introduction section or make a new section. Discuss its various virulence factors and their role in biofilm formation and pathogenicity. Also mention the implications of P. aeruginosa in the healthcare system, food industry, etc. You may add some details from https://doi.org/10.1007/s42770-021-00624-x, https://doi.org/10.1002/jobm.202000678, https://doi.org/10.1016/j.micres.2022.127173 We greatly appreciate the comments you have provided and consider it very appropriate to include the information you requested. For this reason, a paragraph has been included providing more details on the pathogenicity of P. aeruginosa, mentioning the different virulence factors of the bacterium. Another paragraph has been added with more details on the biofilms formed by the bacterium and their relationship with Quorum Sensing. Additionally, a paragraph has been included explaining the issues related to P. aeruginosa in the food industry.3. Can we target IQS system for drug designing against P. aeruginosa. Discuss in detail.It is challenging to establish a therapeutic system targeting the IQS system because it is not entirely clear whether it functions as a true Quorum Sensing system. Additionally, the receptor and the gene cluster responsible for its biosynthesis have not been fully identified. Without a clear understanding of these fundamental aspects, designing drugs specifically targeting the IQS system is highly complex.