Therapeutic potential of kaempferol on Streptococcus pneumoniae infection |
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Institution: | 1. State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China;2. Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China;3. The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China;4. College of Animal Science of Guizhou University, Guiyang, Guizhou, China |
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Abstract: | Co-infections with pathogens and secondary bacterial infections play significant roles during the pandemic coronavirus disease 2019 (COVID-19) pathogenetic process, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Notably, co-infections with Streptococcus pneumoniae (S. pneumoniae), as a major Gram-positive pathogen causing pneumonia or meningitis, severely threaten the diagnosis, therapy, and prognosis of COVID-19 worldwide. Accumulating evidences have emerged indicating that S. pneumoniae evolves multiple virulence factors, including pneumolysin (PLY) and sortase A (SrtA), which have been extensively explored as alternative anti-infection targets. In our study, natural flavonoid kaempferol was identified as a potential candidate drug for infection therapeutics via anti-virulence mechanisms. We found that kaempferol could interfere with the pore-forming activity of PLY by engaging with catalytic active sites and consequently inhibit PLY-mediated cytotoxicity. Additionally, exposed to kaempferol significantly reduced the SrtA peptidase activity by occupying the active sites of SrtA. Further, the biofilms formation and bacterial adhesion to the host cells could be significantly thwarted by kaempferol incubation. In vivo infection model by S. pneumoniae highlighted that kaempferol oral administration exhibited notable treatment benefits, as evidenced by decreased bacterial burden, suggesting that kaempferol has tremendous potential to attenuate S. pneumoniae pathogenicity. Scientifically, our study implies that kaempferol is a promising therapeutic option by targeting bacterial virulence factors. |
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Keywords: | Pneumolysin Sortase A Anti-virulence Kaempferol CDC"} {"#name":"keyword" "$":{"id":"kwrd0040"} "$$":[{"#name":"text" "_":"cholesteroldependent cytolysin CFU"} {"#name":"keyword" "$":{"id":"kwrd0050"} "$$":[{"#name":"text" "_":"colony forming units CMC"} {"#name":"keyword" "$":{"id":"kwrd0060"} "$$":[{"#name":"text" "_":"sodium carboxymethylcellulose COVID-19"} {"#name":"keyword" "$":{"id":"kwrd0070"} "$$":[{"#name":"text" "_":"coronavirus disease 2019 CV"} {"#name":"keyword" "$":{"id":"kwrd0080"} "$$":[{"#name":"text" "_":"crystal violet FRET"} {"#name":"keyword" "$":{"id":"kwrd0090"} "$$":[{"#name":"text" "_":"fluorescence resonance energy transfer HylA"} {"#name":"keyword" "$":{"id":"kwrd0100"} "$$":[{"#name":"text" "_":"hyaluronidase MOI"} {"#name":"keyword" "$":{"id":"kwrd0110"} "$$":[{"#name":"text" "_":"multiplicity of infection NanA"} {"#name":"keyword" "$":{"id":"kwrd0120"} "$$":[{"#name":"text" "_":"Neuraminidase A PLY"} {"#name":"keyword" "$":{"id":"kwrd0130"} "$$":[{"#name":"text" "_":"pneumolysin RBCs"} {"#name":"keyword" "$":{"id":"kwrd0140"} "$$":[{"#name":"text" "_":"rabbit red blood cells SARS-CoV-2"} {"#name":"keyword" "$":{"id":"kwrd0150"} "$$":[{"#name":"text" "_":"Severe Acute Respiratory Syndrome Coronavirus 2 SrtA"} {"#name":"keyword" "$":{"id":"kwrd0170"} "$$":[{"#name":"text" "_":"sortase A |
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