Screening of Pandemic Response Box Library Reveals the High Activity of Olorofim against Pathogenic Sporothrix Species
, Rodrigo Rollin-Pinheiro 2, Yasmin da Silva Fontes 3, Giulia Maria Pires dos Santos 1,2, Glauber Ribeiro de Sousa Araújo 4, Anderson Messias Rodrigues 5, Allan J. Guimarães 6, Wanderley de Souza 7, Susana Frases 4, Antonio Ferreira-Pereira 3, Eliana Barreto-Bergter 2 and Sonia Rozental 1Round 1
Reviewer 1 Report
Sporothrix species are dimorphic pathogenic fungi. Why the yeast for of species was only used for antifungal susceptibility?
Author Response
Reviewer 1:
Sporothrix species are dimorphic pathogenic fungi. Why the yeast for of species was only used for antifungal susceptibility?
Answer: The filamentous form and the yeast phase of Sporothrix spp. do not exhibit the same susceptible profile against antifungal agents [doi: 10.1093/mmy/myu056]. Therefore, we used only Sporothrix yeasts in our studies because they are found in the host during sporotrichosis manifestations as the parasitic form of Sporothrix species (line 85).
Reviewer 2 Report
The work of Borba-Santos and cols. is an interesting and robust research article in which they screened the Pandemic Response Box library (Medicines for Malaria Venture) of 400 diverse molecules against Sporothrix pathogenic species, revealing a high antifungal activity of Olorofim against these dimorphic fungi. In general, the experimental design of the work, as well as the methods adopted were adequate and consistent with the planted objectives. Moreover, the manuscript is adequately structured and well written.
The work is very informative and I recommend the acceptance in its present form.
Author Response
Reviewer 2:
The work of Borba-Santos and cols. is an interesting and robust research article in which they screened the Pandemic Response Box library (Medicines for Malaria Venture) of 400 diverse molecules against Sporothrix pathogenic species, revealing a high antifungal activity of Olorofim against these dimorphic fungi. In general, the experimental design of the work, as well as the methods adopted were adequate and consistent with the planted objectives. Moreover, the manuscript is adequately structured and well written.
The work is very informative and I recommend the acceptance in its present form.
Answer: We thank Reviewer 2 for their comments.
Reviewer 3 Report
It's a very good work, I just have one question:
Why work with 7-day-old yeast cells? They are not in an already advanced process in terms of their metabolism, have you thought to see what happens with younger cells (3-4 days)?
There are reports mentioning cell wall bilayers after 7 days in S. schenckii and S. brasiliensis yeasts and maybe in younger cells the effects of Olorofomin are more drastic.
Author Response
Reviewer 3:
It's a very good work, I just have one question:
Why work with 7-day-old yeast cells? They are not in an already advanced process in terms of their metabolism, have you thought to see what happens with younger cells (3-4 days)?
There are reports mentioning cell wall bilayers after 7 days in S. schenckii and S. brasiliensis yeasts and maybe in younger cells the effects of Olorofomin are more drastic.
Answer: We thank Reviewer 3 for their comments. Evaluation of oloforim effects against younger cells would be interesting; however, the slow growth of the fungus is a limitation. After 3-4 days, we could not obtain enough yeast concentration to perform the experiments, considering our methodology to obtain these cells (lines 78-85).
Reviewer 4 Report
Your presentation is very interesting, the study was very well planned and written . I have only suggestion to make, change in line 79, page 2, the word filamentous by mycelial
Author Response
Reviewer 4:
Your presentation is very interesting, the study was very well planned and written . I have only suggestion to make, change in line 79, page 2, the word filamentous by mycelial
Answer: We thank Reviewer 4 for their comments. The modifications suggested by Reviewer 4 were performed.
