Figure 1.

The growth of S. aureus (ATCC® 25904™) and MRSA (ATCC® BAA1717™) was inhibited by SLs 5-29. (A) The X-ray crystallographic structure of SLs 5-29 and the screened SLs compounds. (B) Left panel: The transparency of S. aureus (ATCC® 25904™), showed as SA, co-cultured with different concentrations of SLs 5-29 (2, 5 and 10 μM) for 10 h, with DMSO and ampicillin (50 μg/mL) as control; Middle panel: The growth of S. aureus (ATCC® 25904™) after cultured with SLs 5-29 for 5 h by plate counting; Right panel: The growth of S. aureus (ATCC® 25904™) after being cultured with SLs 5-29 for 10, 15 and 20 h as assessed by plate counting. (C) Left panel: The transparency of MRSA (ATCC® BAA1717™) co-cultured with different concentrations of SLs 5-29 (1, 2, 5 and 10 μM) for 10 h, with DMSO as control; Middle panel: The growth of MRSA (ATCC® BAA1717™) after cultured with SLs 5-29 for 5 h by plate counting; Right panel: The growth of MRSA (ATCC® BAA1717™) after being cultured with SLs 5-29 for 10, 15 and 20 h as assessed by plate counting. (D) The numbers of bacteria in the peripheral blood after being infected with MRSA (ATCC® BAA1717™) for 24 and 48 h as assessed by plate counting (Vac, vancomycin). (E) The survival times were monitored. (F) Left panel: RNAseq data of S. aureus (ATCC® 25904™) co-cultured with SLs 5-29 for 10 h showing the oppA, oppB, oppC, oppD, oppF, opuCB, opuCC and opuCD genes were down-regulated; Right panel: Q-PCR was used to verify the results of RNAseq data. (G) Diagrammatic representation of the action mechanism of SLs 5-29 inhibition of S. aureus bacteria: SLs 5-29 blocked the transport channels of nutrients or signaling molecules and osmoprotectants by binding to the oligopeptide permeases, oppB, oppC and oppD, and the osmoprotectant uptake of opuCB and opuCD in gram-positive bacteria. All results were carried out at least in triplicates and the Student's t-test was used for two-group comparisons; ∗P < 0.05, ∗∗P < 0.01 and ∗∗∗P < 0.001; mean ± SEM. n = 8.