開發全新種類抗生素—有機碲化合物應用於細菌感染症治療
開發全新種類抗生素—有機碲化合物應用於細菌感染症治療
這項研究最初關注對抗藥性的鮑氏不動桿菌和克雷伯氏肺炎菌等院內感染細菌的治療。研究者們通過體外和體內實驗評估治療效果，在敗血症感染模型中取得了相當好的治療成果。
淋病是一種性傳播疾病，每年全球約有8700萬人受感染。症狀包括排尿疼痛、外陰疼痛、異常分泌等。值得注意的是，有高達56%的男性和80%的女性患者沒有明顯的症狀，這使得感染的傳播難以追蹤，可能導致病例數被低估。近年來，旅行和複雜的性關係使得淋病的傳播更加嚴重。淋病與人類免疫缺陷病毒（HIV）的合併感染對醫療系統構成了更大的負擔。在台灣，淋病雙球菌的抗藥性問題逐漸嚴峻，使得經驗性治療的選擇受到限制。美國CARB-X基金計畫甚至在2023年招募了淋病雙球菌的新藥開發計畫，突顯了對新興治療方法的需求。
研究小組進行了科技部項目的評估，發現一種有機碲化合物AS101-003對淋病雙球菌具有抗菌效果。相比其他革蘭氏陰性細菌，AS101-003表現出更好的抗菌能力。對大多數革蘭氏陰性細菌的最小抑制濃度（MIC）為<0.25~16 μg/ml，而對淋病雙球菌的最小抑菌濃度更僅為<0.015625~0.5 μg/ml，可見該藥物對於淋病雙球菌的治療潛力。此外，團隊成功建立了淋病雙球菌在小鼠陰道感染的模型，就我們所知是台灣成功建立該模式的研究團隊。經AS101-003治療後，菌量下降了90%以上，顯示出AS101-003有望成為淋病雙球菌的有效治療藥物。相關研究也獲得2023年國家新創精進獎的肯定。
圖形摘要
應用與亮點：
1.有機碲化合物AS101-003對於淋病雙球菌具有更強力的抗菌活性。
2.建立淋病雙球菌在小鼠陰道感染模型的台灣先鋒團隊。
【研究團隊】
團隊成員：
曾嵩斌、盧柏樑、楊宗穎
代表單位：高雄醫學大學 醫學檢驗生物技術學系
團隊簡介：
醫技系 曾嵩斌老師實驗室團隊，也為高雄醫學大學SPARK TAIWAN (台灣生醫與醫材轉譯加值人才培訓計畫)藥品輔導團隊之一。抗藥性細菌的感染已是全球醫學臨床之普遍問題，抗藥性細菌中最嚴重的問題係「碳青黴素抗藥性」，此問題也被WHO列為目前急需開發新興抗生素的極度優先。然而全新種類 (first-in-class)的抗生素開發困難，導致藥廠僅能以相似結構或搭配抑制劑加以改良，而這種新皮舊骨的抗生素容易引起的抗藥性問題再次產生，使藥物快速失去效果。團隊目前開發了新興小分子化合物抗生素，較現行臨床用藥具更好治療效果，目前已通過美國專利臨時案，未來將進一步完成臨床前試驗並申請試驗性新藥資格，而後希望技轉予藥廠，藉此為臨床抗藥性細菌問題締造生機。
研究聯繫Email：曾嵩斌 tsengsp@kmu.edu.tw
【論文資訊】
論文出處：Microbiol Spectr. 2023 Mar-Apr; 11(2): e01496-22.
全文下載：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10100759/
Development of tellurium-containing compounds as a first-in-class antibiotic
Development of tellurium-containing compounds as a first-in-class antibiotic
This research initially focused on the treatment of antibiotic-resistant bacteria such as Acinetobacter baumannii and Klebsiella pneumoniae, which are commonly associated with hospital-acquired infections. The team evaluated the therapeutic effects through both in vitro and in vivo experiments, achieving significant positive outcomes in a sepsis infection model.
Gonorrhea is a sexually transmitted disease that affects approximately 87 million people globally each year. Symptoms include painful urination, genital pain, abnormal discharge, and, notably, up to 56% of males and 80% of females may be asymptomatic, making the tracking of transmission difficult and potentially leading to underestimated case numbers. In recent years, increased travel and complex sexual relationships have exacerbated the spread of gonorrhea. The concurrent infection of gonorrhea and human immunodeficiency virus (HIV) poses an even greater burden on healthcare systems. In Taiwan, the emergence of antibiotic-resistant Neisseria gonorrhoeae has restricted the options for empirical treatment. The U.S. CARB-X fund even recruited a new drug development project for Neisseria gonorrhoeae in 2023, highlighting the demand for innovative treatment approaches. The research team conducted an evaluation under the Ministry of Science and Technology project and discovered that the organic tellurium compound AS101-003 has antibacterial effects against N. gonorrhoeae. In comparison to other Gram-negative bacteria, AS101-003 exhibited superior antibacterial capabilities. The minimum inhibitory concentration (MIC) for most Gram-negative bacteria ranged from <0.25 to 16 μg/ml, while the MIC for N. gonorrhoeae was only <0.015625 to 0.5 μg/ml, approximately more than 10 times lower. Additionally, the team successfully established a mouse vaginal infection model for N. gonorrhoeae, making them the first research team in Taiwan to achieve this. After treatment with AS101-003, the bacterial load decreased by more than 90%, indicating the potential efficacy of AS101-003 as a treatment for N. gonorrhoeae.
Graphical Abstract
Application and Highlights:
1.The organic tellurium compound AS101-003 exhibits superior antibacterial activity against Neisseria gonorrhoeae.
2.The team has achieved a significant milestone in Taiwan by successfully creating a mouse vaginal infection model for
Neisseria gonorrhoeae.
Research Team Members:
Tseng Sung-Pin,Lu Po-Liang,Yang Tsung-Ying
Representative Department: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University
Introduction of Research Team:
The laboratory team of Dr. Tseng Sung-Pin from the Department of Medical Technology at Kaohsiung Medical University is part of the pharmaceutical counseling teams of SPARK TAIWAN. Drug-resistant bacteria is a common problem in global medical clinics. The most serious problem is Carbapenem resistance. Developing new antibiotics is difficult, so pharmaceutical companies improve existing ones. The team has developed a new small molecule compound antibiotic that is more effective than current clinical drugs. It has a provisional US patent. They will complete preclinical tests and apply for qualification as an experimental new drug. They hope to transfer the technology to a pharmaceutical company to address drug-resistant bacteria.
Contact Email:
Tseng Sung-Pin tsengsp@kmu.edu.tw
Publication: Microbiol Spectr. 2023 Mar-Apr; 11(2): e01496-22.
Full-Text Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10100759/
