Advancing Pathogen Genomics: A Comprehensive Review of the Xanthomonas(*) Genome's Impact on Bacterial Research and Control Strategies

Dear colleagues from the Managing Board of PCI Infections,
Dear Damien,
 
First of all, we would like to thank you for editing our manuscript. Special thanks go to the four reviewers for their positive and encouraging comments. 
 
We have addressed and corrected all points raised by Reviewer 4 (Boris Vinatzer). 
 
Anonymous reviewers 2 and 3 had no specific comments that needed to be considered in the revision of the manuscript.
 
Anonymous Reviewer 1 had the most comments, which we have addressed as explained below. Some comments called for further discussion on possible applications or implications. In order to maintain the balance of the individual contributions in this article, we have tried not to go into too much detail, but have nevertheless outlined important developments.
 
Our revisions are visible in the uploaded document with the modifications marked in TrackChange mode.
 
We hope that our revised manuscript is now suitable for publication in PCI Infections.
 
With kind regards,
Ralf Koebnik
 
 
 
Response to Reviewer 1:
 
Reviewer 1 – Page 7-9:
-The section could benefit from clearer organization and structure. It transitions between different topics, including the use of ancient DNA and taxonomic studies, without a clear delineation.
-The section could engage the reader more effectively by providing a clearer introduction or context for the importance of ancient genomics and taxonomic studies in the field of plant pathology. This would help readers understand why these topics are significant.
 
Our answer: We have reorganized this section and hope that it is now clearer. We prefer not to include taxonomic studies here, as this aspect will be developed later by Marion Fischer-Le Saux. However, we have changed the introduction on genomics and added a conclusion to the second paragraph to better structure the transition between the two paragraphs.
 
Reviewer 1 – Pages 10-22:
Constantin and Co-workers' Taxonomic Reclassification: The work by Constantin and co-workers on the taxonomic reclassification of Xanthomonas strains is commendable. However, it's essential to acknowledge that there are still unresolved taxonomic issues, particularly in Rademaker group 9.1 and some unclassified pathovars. The absence of a clear classification for these strains might hinder precise research and diagnostics in the field. Addressing these ambiguities should be a priority for future taxonomic studies.
 
Our answer: We have commented on the problem with Rademaker group 9.1, which was unfortunately not addressed by Constantin et al. in their study on the taxonomic revision of the so-called X. axonopodis species complex, which correspond to Rademaker group 9. 
 
Reviewer 1 – Emergence of Xylella fastidiosa in Europe:
The emergence of Xylella fastidiosa and its comparison with Xanthomonas is indeed a fascinating area of research. However, it's important to note that while these bacteria share phylogenetic relations, their biological characteristics and niches significantly differ. The section provides valuable insights into the epidemiology and ecological impact of X. fastidiosa, but further discussions on potential preventive measures and strategies to mitigate its spread would be beneficial.
 
Our answer: We have added our perspective on potential preventive measures and strategies to mitigate its spread. 
 
Reviewer 1 – Type 4 Protein Secretion and Bacterial Competition: The discovery of type 4 protein secretion as a mechanism for bacterial competition in Xanthomonas is groundbreaking. However, this subsection primarily focuses on the historical context and initial discoveries. To enhance the reader's understanding, it would be helpful to include more recent developments and ongoing research in this area. Additionally, discussing potential applications or implications of this discovery in biotechnology or agriculture could add value. 
 
Our answer: We have added some implications of this discovery in the context of biological control, where two genera related to Xanthomonas, Lysobacter and Stenotrophomonas, contain potential biological control organisms and where knowledge of contact-dependent killing will facilitate the engineering of beneficial synthetic communities.
 
Reviewer 1 – Cracking the DNA-binding Code of TAL Effectors: The TAL effector research has indeed been a captivating field, especially with the discovery of the TAL code. However, the subsection briefly mentions this significant discovery without delving into its broader implications or recent advancements. Providing more context on how this code has revolutionized our understanding of TAL effectors and its applications
 
Our answer: We have added some stunning applications of TALENs and discuss their advantages over CRISPR-Cas technologies in the context of organelle genome engineering. Such striking applications are of course a matter of taste, and as this essay reflects the personal opinions of the authors, others may think of other applications in this rapidly developing field.