Objectives In the past few decades, multiple-antibiotic-resistant Staphylococcus aureus has emerged and quickly spread in hospitals and communities worldwide. Additionally, the formation of antibiotic-tolerant persisters and biofilms further reduces treatment efficacy. Previously, we identified a sorafenib derivative, SC5005, with bactericidal activity against MRSA in vitro and in vivo. Here, we sought to elucidate the resistance status, mode of action and anti-persister activity of this compound. Methods The propensity of S. aureus to develop SC5005 resistance was evaluated by assessment of spontaneous resistance and by multi-passage selection. The mode of action of SC5005 was investigated using macromolecular synthesis, LIVE/DEAD and ATPlite assays and DiOC2(3) staining. The effect of SC5005 on the mammalian cytoplasmic membrane was measured using haemolytic and lactate dehydrogenase (LDH) assays and flow cytometry. Results SC5005 depolarized and permeabilized the bacterial cytoplasmic membrane, leading to reduced ATP production. Because of this mode of action, no resistance of S. aureus to SC5005 was observed after constant exposure to sub-lethal concentrations for 200 passages. The membrane-perturbing activity of SC5005 was specific to bacteria, as no significant haemolysis or release of LDH from human HT-29 cells was detected. Additionally, compared with other bactericidal antibiotics, SC5005 exhibited superior activity in eradicating both planktonic and biofilm-embedded S. aureus persisters. Conclusions Because of its low propensity for resistance development and potent persister-eradicating activity, SC5005 is a promising lead compound for developing new therapies for biofilm-related infections caused by S. aureus.

Background Atopic dermatitis (AD) occurs in exclusively breastfed infants. As fatty acids have some immunomodulatory effect, we aimed to investigate the influence of fatty acid compositions in breast milk (BM) on the development of AD in exclusively breastfed infants. Methods We enrolled two‐ to four‐month‐old exclusively breastfed infants. The objective SCORing Atopic Dermatitis (objSCORAD) was evaluated. The lipid layer of BM was analyzed by gas chromatography for fatty acid levels. Medical charts were reviewed. Results Forty‐seven AD infants and 47 healthy controls were enrolled. The objSCORAD was 20.5 ± 1.7 (shown as mean ± SEM) in the AD group. The age, sex, parental atopy history, and nutrient intake of mothers were not significantly different between two groups. The palmitate and monounsaturated fatty acid (MUFA) levels in BM positively correlated with objSCORAD, while caprylate, acetate, and short‐chain fatty acid (SCFA) levels negatively correlated with objSCORAD (p = .031, .019, .039, .013, .022, respectively). However, the butyrate levels in BM were not significantly different. The caprylate and acetate levels in BM were significantly associated with the presence of infantile AD (p = .021 and .015, respectively) after adjusting for age, sex, parental allergy history, MUFA, palmitate, and SCFA levels in BM. ObjSCORAD in infancy was significantly associated with persistent AD (p = .026) after adjusting for age, sex, parental atopy history, caprylate, palmitate, MUFA, acetate, and SCFA levels in BM. Conclusion Caprylate and acetate levels in BM for exclusively breastfed infants were negatively associated with objSCORAD. Lower caprylate and acetate in BM might be the risk factors for infantile AD, while butyrate in BM was not associated with infantile AD.