Next Article in Journal
Therapeutic Potential of Endophytic Microbes: Emphasizing Both Fungal and Bacterial Endophytes
Previous Article in Journal
Quinolone and Colistin Resistance Genes in Extended-Spectrum Beta-Lactamase (ESBL)-Producing Escherichia coli of Diverse Phylogenetic Groups Isolated from Seafood in Mumbai, India
 
 
Review
Peer-Review Record

TtsI: Beyond Type III Secretion System Activation in Rhizobia

Appl. Microbiol. 2025, 5(1), 4; https://doi.org/10.3390/applmicrobiol5010004
by Irene Jiménez-Guerrero 1, Sebastián Acosta-Jurado 1, Pilar Navarro-Gómez 1, Francisco Fuentes-Romero 1, Cynthia Alías-Villegas 2, Francisco-Javier López-Baena 1 and José-María Vinardell 1,*
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Reviewer 3: Anonymous
Appl. Microbiol. 2025, 5(1), 4; https://doi.org/10.3390/applmicrobiol5010004
Submission received: 2 December 2024 / Revised: 20 December 2024 / Accepted: 3 January 2025 / Published: 5 January 2025

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 

Authors presented a concise review of rhizobial TtsI, a well-known activator for T3SS and T3E genes. In addition to its conserved target genes and related regulators in the regulon responding to host symbiotic signals, this review highlighted the importance of some other TtsI target genes in the rhizobium-legume symbiosis. As discussed in this review, these non-canonical targets showed a species-dependent pattern and in most cases have not been thoroughly studied. This reviewer enjoyed reading this paper and believe that this review car inspire more efforts to explore unknown symbiotic roles of TtsI regulon. 

 

 

Minor points:   

L30, "C" and "E". It is better to show the full name here.

Figure 1, "Rhizobium" . The common name "rhizobium" or "rhizobia" seems to be more appropriate than the genus name "Rhizobium" in this context.

L212, "Zin-finger" is supposed to be Zinc-finger.

 

Author Response

Reviewer 1:

Authors presented a concise review of rhizobial TtsI, a well-known activator for T3SS and T3E genes. In addition to its conserved target genes and related regulators in the regulon responding to host symbiotic signals, this review highlighted the importance of some other TtsI target genes in the rhizobium-legume symbiosis. As discussed in this review, these non-canonical targets showed a species-dependent pattern and in most cases have not been thoroughly studied. This reviewer enjoyed reading this paper and believe that this review car inspire more efforts to explore unknown symbiotic roles of TtsI regulon. 

 

Thank you very much for your kind comments. We have followed all your suggestions:

Minor points:   

L30, "C" and "E". It is better to show the full name here.

Done.

Figure 1, "Rhizobium" . The common name "rhizobium" or "rhizobia" seems to be more appropriate than the genus name "Rhizobium" in this context.

Done.

L212, "Zin-finger" is supposed to be Zinc-finger.

Corrected.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

This is a well written review that addresses what we currently know about TtsI, the regulator of type 3 secretion system production in rhizobia.  ttsI gene is activated by NodD in most cases, and regulates the secretion of factors that can alter the symbiotic interaction (eg. blocking nodulation on some specific hosts or expanding host range in other cases).  The authors point other roles of this regulatory system in things like motility and biofilm formation.   

Overall I found it interesting and up to date, and I don't have a lot of criticisms.  I would only recommend:

1. Fixing a few minor grammar issues

2. Adding information (perhaps a table ?) indicating, to the extent possible, the frequency of occurrence of T3SS in various rhizobial species - for example I think most strains of S. meliloti and R. leguminosarum species complex don't have them.

3.  It is a bit of an oversight not to mention that in some cases, the function of T3SS can be assumed by other systems.  I am thinking particularly of Mesorhizobium japonicum (formerly loti), where some of the things (including the same effectors if I recall correctly) mediated by T3SS in MAFF303099 are carried out by the T4SSS in the related strain R7A.  I think there are two papers from the Ronson lab (first Author A. Hubber) that describe this.  A statement to this effect might be added around lines 118 to 124

Author Response

This is a well written review that addresses what we currently know about TtsI, the regulator of type 3 secretion system production in rhizobia.  ttsI gene is activated by NodD in most cases, and regulates the secretion of factors that can alter the symbiotic interaction (eg. blocking nodulation on some specific hosts or expanding host range in other cases).  The authors point other roles of this regulatory system in things like motility and biofilm formation.  

Thank you very much for your kind comments. We have followed all your suggestions:

Overall I found it interesting and up to date, and I don't have a lot of criticisms.  I would only recommend:

 

  1. Fixing a few minor grammar issues

We have revised the manuscript in order to fix these issues.

  1. Adding information (perhaps a table ?) indicating, to the extent possible, the frequency of occurrence of T3SS in various rhizobial species - for example I think most strains of S. meliloti and R. leguminosarum species complex don't have them.

Thank you for this suggestion. We have included new Table 1 summarising the current knowledge about the presence of T3SS, T4SS and T6SS in rhizobia.

  1. It is a bit of an oversight not to mention that in some cases, the function of T3SS can be assumed by other systems. I am thinking particularly of Mesorhizobium japonicum (formerly loti), where some of the things (including the same effectors if I recall correctly) mediated by T3SS in MAFF303099 are carried out by the T4SSS in the related strain R7A.  I think there are two papers from the Ronson lab (first Author A. Hubber) that describe this.  A statement to this effect might be added around lines 118 to 124

Again, thank you very much for your comment. We have added information about the presence and symbiotic relevance of T4SS and T6SS in different rhizobia strains. Please, see Table 1, lines 87-102, 124-129, and 151-155.

Reviewer 3 Report

Comments and Suggestions for Authors

The review question related to the main role of ttsI gene is already known for the activation of the rhizobial Type 3 Secretion System. In response to plant-made flavonoids and via binding to specific nod box regulatory sequences, transcription regulators of the NodD family activate nod genes as well as ttsI (Krause A, et al. 2002; Viprey V et al. 1998). Once expressed, the transcriptional activator TtsI binds to conserved promoter sequences called tts boxes found upstream of genes and operons coding for T3SS components and T3Es (Marie C et al. 2004; Lopez-Baena FJ et al. 2008; Wassem R, et al. 2008; Zehner S et al 2008; Krause A et al. 2002; Bolzan de Campos S et al. 2011). Interestingly, TtsI may regulate functions other than those needed for T3SSs, like in Ensifer fredii strain NGR234, where TtsI also activates loci needed for modifying lipopolysaccharides (LPS) into a symbiotically active form called rhamnan (Marie C et al. 2004; Reuhs BL et 2005). In contrast, activation of T3SS functions in C. taiwanensis was reported to be independent of both flavonoids and TtsI, whereas it was triggered by glutamate, like in plant pathogens such as Ralstonia solanacearum and Pseudomonas aeruginosa (Saad MM et al. 2012).

For more imformations you can check the refrence (Albin Teulet et al. 2022)

 No novelty and implication of the paper was highlighted throughout this review compared to the last paper published by the same author (Irene Jiménez-Guerrero et al. 2022) and the other existing literature, with no interest to the readers.

Author Response

The review question related to the main role of ttsI gene is already known for the activation of the rhizobial Type 3 Secretion System. In response to plant-made flavonoids and via binding to specific nod box regulatory sequences, transcription regulators of the NodD family activate nod genes as well as ttsI (Krause A, et al. 2002; Viprey V et al. 1998). Once expressed, the transcriptional activator TtsI binds to conserved promoter sequences called tts boxes found upstream of genes and operons coding for T3SS components and T3Es (Marie C et al. 2004; Lopez-Baena FJ et al. 2008; Wassem R, et al. 2008; Zehner S et al 2008; Krause A et al. 2002; Bolzan de Campos S et al. 2011). Interestingly, TtsI may regulate functions other than those needed for T3SSs, like in Ensifer fredii strain NGR234, where TtsI also activates loci needed for modifying lipopolysaccharides (LPS) into a symbiotically active form called rhamnan (Marie C et al. 2004; Reuhs BL et 2005). In contrast, activation of T3SS functions in C. taiwanensis was reported to be independent of both flavonoids and TtsI, whereas it was triggered by glutamate, like in plant pathogens such as Ralstonia solanacearum and Pseudomonas aeruginosa (Saad MM et al. 2012).

For more imformations you can check the refrence (Albin Teulet et al. 2022)

 No novelty and implication of the paper was highlighted throughout this review compared to the last paper published by the same author (Irene Jiménez-Guerrero et al. 2022) and the other existing literature, with no interest to the readers.

Thank you very much for your comments.

As you may expect (since we are the authors of the present manuscript), we are in complete disagreement with your observation: “No novelty and implication of the paper was highlighted throughout this review compared to the last paper published by the same author (Irene Jiménez-Guerrero et al. 2022) and the other existing literature, with no interest to the readers.”

As you know, there are various recent reviews about the rhizobial T3SS, including those two that you mention: Teulet et al. 2022 and Jiménez-Guerrero et al. 2022. Both of them make an exhaustive revision of the knowledge of the functioning and symbiotic involvement of the rhizobial T3SS. However, the purpose of the present manuscript is other, as it is stated in the title: we were interested in joining in a single manuscript the scattered and widespread information about other roles, nor of the T3SS, but of TtsI as a regulatory protein. To us it has been very surprising that TtsI have been found to control either swimming or surface motility, or the expression of various genes not related, directly at least, to T3SS, including different transcriptional regulators. Although this “new” roles of TtsI have only been found in certain rhizobia, maybe it can be found to be more usual if these kind of studies would be extended to other rhizobia harbouring this transcriptional regulator. And, this is precisely, the spirit of our manuscript: to encourage new studies about other putative roles of TtsI in other rhizobia. In words of reviewer 1: “this reviewer believe that this review can inspire more efforts to explore unknown symbiotic roles of TtsI regulon”.

Back to TopTop