| dc.description.abstract | Probiotic bacteria, in which commensal bacteria are used to prevent the colonization of the host by pathogens, have been shown to be a promising modality for the prevention and treatment of infections. The methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) has become a major threat to public health and soft tissue infections. It remains an unmet challenge to develop effective therapeutic approaches for MRSA treatment because of its formidable resistance against multiple traditional antibiotics. The first study showed that commensal S. aureus bacteria isolated from human skin demonstrated the ability to mediate the glycerol fermentation to produce short-chain fatty acids (SCFAs), which can be defined as a part of skin innate immunity to inhibited the growth of USA300. Quantitative proteomic analysis of enzymes involved in glycerol fermentation demonstrated that the expression levels of six enzymes, including glycerol-3-phosphate dehydrogenase (GPDH) and phosphoglycerate mutase (PGM), in commensal S. aureus are more than three-fold higher than those in USA300. Western blotting validated the low expression levels of GPDH in USA300, MRSA252 (a strain of hospital-acquired MRSA), and invasive methicillin-susceptible S. aureus (MSSA). In the presence of glycerol, commensal S. aureus effectively suppressed the growth of USA300 in vitro and in vivo. Active immunization of mice with lysates or recombinant α-hemolysin of commensal S. aureus or passive immunization with neutralizing sera provided immune protection against the skin infection of USA300. As antibodies could offer protection against S. aureus infection, we speculated that natural antibodies in the bloodstream provoked by commensal S. aureus are a crucial part of host adaptive immunity to prevent the colonization of USA300 MRSA.
MRSA is often isolated from patient wounds, either in the hospital and community setting. Choosing a suitable dressing for any wound, including those colonized or infected with MRSA, should be determined by the type of wound a patient has in line with the principles of asepsis and moist wound healing. Due to hydrogels′ peculiar properties, such as high-sensitive to physiological environments, hydrophilic nature, soft tissue-like water content, and adequate flexibility, make them excellent candidates for biomedical applications. In the second study, we created a cysteine-capped hydrogel able to absorb and release copper, an ion with the capability of suppressing the growth of USA300, a community-acquired MRSA. The results of the analysis of Fourier transform infrared spectroscopy (FTIR) revealed the binding of copper to a cysteine-capped hydrogel. The topical application of a cysteine-capped hydrogel binding with copper on USA300-infected skin wounds in the dorsal skin of the Institute of Cancer Research (ICR) mice significantly enhanced wound healing, hindered the growth of USA300, and reduced the production of pro-inflammatory macrophage inflammatory protein 2-alpha (MIP-2) cytokine. Our work demonstrates a newly designed hydrogel that conjugates a cysteine molecule for copper binding. The cysteine-capped hydrogel can potentially chelate various antimicrobial metals as a novel wound dressing.
Not only in the skin, but the presence of gut probiotic in the body has beneficial effects. The gut probiotic is capable of regulating nutrients acquisition throughout the body and eventually bodyweight, leading to the development of several diseases, including obesity. The third study aimed to investigate the probiotic effect of Leuconostoc mesenteroides (L. mesenteroides) on high-fat diet (HFD)-induced Peroxisome proliferator-activated receptor gamma (PPAR-γ) activation and abdominal fat depots. Incubation of differentiated 3T3-L1 adipocytes with media of L. mesenteroides EH-1, a butyric acid-producing strain, significantly reduced the amounts of lipid droplets. The oral administration of L. mesenteroides EH-1 produced large amounts (>1 mM) of butyric acid in the cecum and attenuated the HFD-induced upregulation of PPAR-γ and accumulation of abdominal fats in mice. The combination of 2% glucose with L. mesenteroides EH-1 increased the production of butyric acid and potentiated the probiotic activity of L. mesenteroides EH-1 against the formation of lipid droplets in 3T3-L1 adipocytes as well as abdominal fats in HFD-fed mice. The inhibition of free fatty acid receptor 2 (Ffar2) by its antagonist, GLPG-0974, markedly diminished the probiotic effects of L. mesenteroides EH-1 plus glucose on the suppression of HFD-induced PPAR-γ and abdominal fats. Besides demonstrating the probiotic value of L. mesenteroides EH-1, our results highlight the possible therapy targeting the butyric acid-activated Ffar2 pathway to reduce abdominal fats. | en_US |