Title: The SCID Mouse Model for Identifying Virulence Determinants in Coxiella burnetii

DOI: 10.3389/fcimb.2017.00025

This study describes a SCID mouse model of Coxiella burnetii infection for predicting virulence factors, in either independent or competitive infections. Following assessment of mouse strain and bacterial dose, the SCID mouse model was used for testing C. burnetii NMII mutants for virulence. In addition, an intra-tracheal challenge was assessed as a comparison of route of infection. It is well written manuscript with a thorough literature review on what is already known about C. burnetii infection models and virulence factors. The clarity of article could be improved, particularly in the results section, as outlined in my comments below.

1. On page 5, in the first paragraph of the results section, the text refers to Figure 1B as being statistically significant, however it is not clear from the figure that it is and what statistical analysis was used to test this. Similarly for A, C and D of Figure 1, if statistical analyses were performed (although not significant) it would be useful to state in the figure legend.

2. There is a large amount of data that were not shown, however it would be useful to include them as supplementary figures so readers can see the raw data. For readability and clarity, on page 6, it would also be useful to separate the data not shown with those that are shown.

3. The number of mice used in some experiments are not stated, for example Figure 1A and B.

4. The data presented in Figure 2 on page 4 are not described in the figure legend (for example, mean and standard deviation).

5. Statistical analyses was performed on the data on Figure 4A, however for naive and heat-killed groups, the data appear to be zero. Similarly, for Tn::cvpB and Tn::EnhC, there is only one data point. The analysis should be clarified.

6. A direct comparison of intra-peritoneal and intra-tracheal infection routes in the same experiment would be useful to conclude the validity of the IP route.