| dc.description.abstract | Microbiome Precision Editing: Using PEG as a Selective Fermentation Initiator Against Methicillin-resistant Staphylococcus aureus
Recent creation of a Unified Microbiome Initiative (UMI) has the aim of understanding how microbes interact with each other and with us. When pathogenic Staphylococcus aureus (S. aureus) infects the skin, the interplay between S. aureus and skin commensal bacteria occurs. Our previous data revealed that skin commensal bacteria can mediate fermentation against the growth of USA300, a community-acquired methicillin-resistant S. aureus MRSA (CA-MRSA). By using a fermentation process with solid media on a small scale, we define poly(ethylene glycol) dimethacrylate (PEG-DMA) as a selective fermentation initiator (SFI) which can specifically intensify the probiotic ability of skin commensal Staphylococcus epidermidis (S. epidermidis) bacteria. At least five SCFAs including acetic, butyric and propionic acids with anti-USA300 activities were produced by PEG-DMA fermentation of S. epidermidis. Furthermore, the S. epidermidis-laden PEG-DMA hydrogels effectively decolonized USA300 in skin wounds in mice. The PEG-DMA and its derivatives may become novel biomaterials to specifically tailor the human skin microbiome against invading pathogens.
Colonization of Nasal Cavities by Staphylococcus epidermidis Mitigates SARS-CoV-2 Nucleocapsid Phosphoprotein-induced Interleukin (IL)-6 in the Lung
Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger excessive interleukin (IL)-6 signaling, leading to a myriad of biological effects including a cytokine storm that contributes to multiple organ failure in severe coronavirus disease 2019 (COVID-19). Using a mouse model, we demonstrated that nasal inoculation of nucleocapsid phosphoprotein (NPP) of SARS-CoV-2 increased IL-6 content in bronchoalveolar lavage fluid (BALF). Nasal administration of liquid coco-caprylate/caprate (LCC) onto Staphylococcus epidermidis (S. epidermidis)-colonized mice significantly attenuated NPP-induced IL-6. Furthermore, S. epidermidis mediated LCC fermentation to generate electricity and butyric acid that promoted bacterial colonization and activated free fatty acid receptor 2 (Ffar2), respectively. Inhibition of Ffar2 impeded the effect of S. epidermidis plus LCC on the reduction of NPP-induced IL-6. Collectively, these results suggest that nasal S. epidermidis is part of the first line of defense in ameliorating a cytokine storm induced by airway infection of SARS-CoV-2.
Information-based similarity analysis of electric signals of nasally pre-colonized Staphylococcus epidermidis in mice
Many bacteria in the human microbiome have been identified as electrogenic microorganisms. Characterization of bacterial electricity from complex electric signals in vivo relies on a feature extraction method. A Staphylococcus epidermidis (S. epidermidis) K1 strain isolated from human was pre-colonized on the nasal cavities of mice and triggered with liquid coco-caprylate/caprate (LCC) to elicit electricity. Intranasal administration of phosphate buffered saline (PBS) was used to establish a base pattern of electric signals. Compared to PBS, LCC induced a higher level of voltage changes in S. epidermidis K1 colonized nasal cavities. The patterns of electric signals elicited by PBS or LCC were distinctly separated by information-based similarity (IBS) analysis. Treatment of S. epidermidis K1 with roseoflavin significantly diminished the electricity production of S. epidermidis K1 and exhibited electric signals with high similarity to a base pattern. Collectively, our results indicated that commensal electrogenic bacteria contributed to nasal electric signals and highlighted that IBS analysis was a quantitative method to analyze the similarity and regularity of bacteria-involved electric signals.
In recent years, microbiome has been shown to affect and represent the human body, whether on the human surface, in the gastrointestinal tract, in the immune system, or even in the mind. By studying the interaction between microbiome, the more effective treatments for diseases caused by microbial imbalance can be found. The causes of several human diseases can be understood through checking the composition of microbiome. It even represents the health status of human. In this dissertation, I will propose innovative therapeutic and detection methods to address human diseases by studying the skin microbiome and discuss the future perspectives and applications. | en_US |