Staphylococcus aureus Exploits a Non-ribosomal Cyclic Dipeptide to Modulate Survival within Epithelial Cells and Phagocytes
Fig 5
The S. aureus NRPS is required for full virulence in S. aureus-induced pneumonia.
a) Next-generation sequencing of transposon insertion sites was used to detect changes of read frequencies in bacteria from transposon mutant recovered from mouse lungs when compared to the inoculum library. The box and whisker plot represents the median and range of the relative difference (log2 fold change) in frequency of transposon insertion sites detected in ausA (see also S5 Table). b) ausB mutants are attenuated in a pneumonia infection model. S. aureus JE2, an isogenic ausB mutant, as well as the ausB complementation strain were instilled intranasally into Balb/c mice (n = 10) and animal health (disease activity index, DAI) was continuously recorded over 48 hours at the indicated time points. The graph shows mean DAI ± SEM. Statistics were determined by linear models of DAI as a function of infection group and time; *P<0.05. c) In vivo competition of a 1:1 mixture of wild-type and the ausB mutant strain at a sublethal dosage shows that the mutant is outcompeted by the wild-type. Although these effects were subtle, ausB mutants are recovered at reduced frequencies (43.55% of total CFU, P = 0.037 for difference from 50%). d) The resulting competitive index of 0.96 is only slightly, but significantly different from 1 (P = 0.0446).