Combining the In Silico and In Vitro Assays to Identify Strobilanthes cusia Kuntze Bioactives against Penicillin-Resistant Streptococcus pneumoniae

Xiaoyu Han; Lu Jin; Zhimin Zhao; Xinjun Xu; Shiyi Liu; Yuquan Huang; Xiaoli Liu; Yuehong Xu; Depo Yang; Wei Huang; Li Wang

doi:10.3390/ph16010105

Combining the In Silico and In Vitro Assays to Identify Strobilanthes cusia Kuntze Bioactives against Penicillin-Resistant Streptococcus pneumoniae

Pharmaceuticals (Basel). 2023 Jan 10;16(1):105. doi: 10.3390/ph16010105.

Authors

Xiaoyu Han¹, Lu Jin¹, Zhimin Zhao¹, Xinjun Xu¹, Shiyi Liu², Yuquan Huang³, Xiaoli Liu⁴, Yuehong Xu¹, Depo Yang¹, Wei Huang², Li Wang^{4

5}

Affiliations

¹ School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
² Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518001, China.
³ China Resources Sanjiu Medical & Pharmaceutical Co., Ltd., Shenzhen 518110, China.
⁴ Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518000, China.
⁵ Kunpeng Institute of Modern Agriculture at Foshan, Foshan 528225, China.

Abstract

Leaves of Strobilanthes cusia Kuntze (S. cusia) are a widely used alexipharmic Traditional Chinese Medicine (TCM) in southern China for the prevention of cold and respiratory tract infectious diseases. One of the most common bacterial pathogens in the respiratory tract is the gram-positive bacterium Streptococcus pneumoniae. The antibiotic resistance of colonized S. pneumoniae makes it a more serious threat to public health. In this study, the leaves of S. cusia were found to perform antibacterial effects on the penicillin-resistant S. pneumoniae (PRSP). Confocal assay and Transmission Electron Microscopy (TEM) monitored the diminished cell wall integrity and capsule thickness of the PRSP with treatment. The following comparative proteomics analysis revealed that the glycometabolism-related pathways were enriched for the differentially expressed proteins between the samples with treatment and the control. To further delve into the specific single effective compound, the bio-active contents of leaves of S. cusia were analyzed by UPLC-UV-ESI-Q-TOF/MS, and 23 compounds were isolated for anti-PRSP screening. Among them, Tryptanthrin demonstrated the most promising effect, and it possibly inhibited the N-glycan degradation proteins, as suggested by reverse docking analysis in silico and further experimental verification by the surface plasmon resonance assay (SPR). Our study provided a research foundation for applications of the leaves of S. cusia as a TCM, and supplied a bio-active compound Tryptanthrin as a candidate drug skeleton for infectious diseases caused by the PRSP.

Keywords: Strobilanthes cusia; penicillin-resistant Streptococcus pneumoniae; proteomics; reverse docking.

Grants and funding

This study was supported by the Agricultural Science and Technology Innovation and Promotion in Guangdong (No. 2023KJ142), the Provincial Key R&D Program of Guangdong (No. 2020B020221002), the National Key Research and Development Program of China (Grant No. 2020YFA0907900), the National Natural Science Foundation of China (Grant No. 32070242), the National Nature Science Foundation of China (No. 82173859, China), the Shenzhen Key Laboratory of Prevention and Treatment of Severe Infections (ZDSYS20200811142804014, China).