인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Pertussis (whooping cough) is a vaccine-preventable but re-emerging, highly infectious respiratory disease caused by Bordetella pertussis. There are currently no effective treatments for pertussis, complicating care for nonvaccinated individuals, especially newborns. Disease manifestations are predominantly caused by pertussis toxin (PT), a pivotal virulence factor classified as an ADP-ribosylating AB-type protein toxin. In this work, an unbiased approach using peptide libraries, bioassay-guided fractionation and mass spectrometry revealed α<sub>1</sub>-antitrypsin (α<sub>1</sub>AT) as a potent PT inhibitor. Biochemistry-, cell culture-, and molecular modeling-based in vitro experimentation demonstrated that the α<sub>1</sub>AT mode of action is based on blocking PT-binding to the host target cell surface. In the infant mouse model of severe pertussis, α<sub>1</sub>AT expression was reduced upon infection. Further, systemic administration of α<sub>1</sub>AT significantly reduced B. pertussis-induced leukocytosis, which is a hallmark of infant infection and major risk factor for fatal pertussis. Taken together our data demonstrates that α<sub>1</sub>AT is a novel PT inhibitor and that further evaluation and development of α<sub>1</sub>AT as a therapeutic agent for pertussis is warranted. Importantly, purified α<sub>1</sub>AT is already in use clinically as an intravenous augmentation therapy for those with genetic α<sub>1</sub>AT deficiency and could be repurposed to clinical management of pertussis.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.