PREreview of Comparative mortality of dominantStaphylococcus aureuslineages in human bacteremia and animal infection models

This review resulted from the graduate-level course "How to Read and Evaluate Scientific Papers and Preprints" from the University of São Paulo, which aimed to provide students with the opportunity to review scientific articles, develop critical and constructive discussions on the endless frontiers of knowledge, and understand the peer review process.

SUMMARY

This study by Sánchez-Osuna et al. (doi: https://doi.org/10.1101/2025.03.11.642576) describes key molecular mechanisms behind mortality caused by a set of representative Staphylococcus aureus clones, isolated from human bacteremia. The history of clinical outcomes is compared with bacterial experimental behavior observed while avoiding host influences by studying infection in healthy models (Galleria mellonella and rabbit). The authors highlight the variability in S. aureus strains, which is evidenced by differential growth rates and biofilm formation, as well as expression of virulence factors. Transcriptomic analysis shows that ST398, a highly pathogenic strain, up-regulates the expression of a cohort of virulence factors when compared to the less aggressive CC30. In addition to that, agrC plays a crucial role in pathogenicity as the ST398 deficient strain Sau7 is significantly less aggressive. In summary, this manuscript provides valuable information, demonstrating that such animal infection models can be used as homogeneous systems for evaluating lineage-specific pathogens, while also shedding light on molecular mechanisms responsible for virulence in S.aureus.

MAJOR COMMENTS

1. Data from control strains (Newman, SAR5091 and RN4220) should be provided to be more clarifying.

2. In transcriptomic analysis, the authors treat different strains as replicates. Although they explain that the lineages have similar expression patterns, sau-22 and sau-7 exhibit slight differences in survival rates, which could suggest variations in gene expression. The addition of appropriate replicates could benefit the study robustness.

MINOR COMMENTS

1. In Figure 1, perhaps applying iTol’s colored strips or colored ranges to show clonal complexes and agr information could be more illustrative. Also, the spa and SCCmec typing results are interesting data to present.

2. No mention of the 2D figure can be found in the text.

Competing interests

The author declares that they have no competing interests.