윤상선 (University of Cincinnati College of Medicine) | 한빛사논문 > 한빛사

한빛사논문, 상위피인용논문

조회4,994

University of Cincinnati College of Medicine

J. Clin. Invest., Published Online January 26, 2006 Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions

Abstract

Sang Sun Yoon ¹, Ray Coakley ², Gee W. Lau ³, Sergei V. Lymar ⁴, Benjamin Gaston ⁵, Ahmet C. Karabulut ¹, Robert F. Hennigan ⁶, Sung-Hei Hwang ¹, Garry Buettner ⁷, Michael J Schurr ⁸, Joel E. Mortensen ⁹, Jane L. Burns ¹⁰, David Speert ¹¹, Richard C. Boucher ², Daniel J. Hassett ^12*

¹ Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. ² Cystic Fibrosis Pulmonary Research and Treatment Center and Department of Pulmonary Biology, University of North Carolina, Chapel Hill, North Carolina, USA. ³ Pulmonary Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. ⁴ Department of Chemistry, Brookhaven National Laboratory, Upton, New York, USA. ⁵ Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. ,Department of Pediatric Critical Care, University of Virginia School of Medicine, Charlottesville, Virginia, USA. ⁶ Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York, USA. ⁷ Department of Chemistry, University of Iowa, Iowa City, Iowa, USA. ⁸ Department of Microbiology, Tulane University, New Orleans, Louisiana, USA. ⁹ Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. ¹⁰ Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. ¹¹ Department of Pedriatrics, University of British Columbia, Vancouver, British Columbia, Canada. ¹² Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, Ohio 45267-0524, USA. Phone: (513) 558-1154; Fax: (513) 558-8474

Received for publication February 8, 2005, and accepted in revised form November 29, 2005

Abstract

Mucoid, mucA mutant Pseudomonas aeruginosa cause chronic lung infections in cystic fibrosis (CF) patients and are refractory to phagocytosis and antibiotics. Here we show that mucoid bacteria perish during anaerobic exposure to 15 mM nitrite (NO₂^-) at pH 6.5, which mimics CF airway mucus. Killing required a pH lower than 7, implicating formation of nitrous acid (HNO₂) and NO, that adds NO equivalents to cellular molecules. Eighty-seven percent of CF isolates possessed mucA mutations and were killed by HNO₂ (3-log reduction in 4 days). Furthermore, antibiotic-resistant strains determined were also equally sensitive to HNO₂. More importantly, HNO₂ killed mucoid bacteria (a) in anaerobic biofilms; (b) in vitro in ultrasupernatants of airway secretions derived from explanted CF patient lungs; and (c) in mouse lungs in vivo in a pH-dependent fashion, with no organisms remaining after daily exposure to HNO₂ for 16 days. HNO₂ at these levels ofacidity and NO₂^- also had no adverse effects on cultured human airway epithelia in vitro. In summary, selective killing by HNO₂ may provide novel insights into the important clinical goal of eradicating mucoid P. aeruginosa from the CF airways.

논문정보

형식Research article
게재일2006년 01월 (BRIC 등록일 )
연구진국외 연구진
분야
피인용횟수120회 이상 인용된 논문 (상위피인용논문 등록일 2017-03-24)

댓글 작성 로그인

CV 열람하기

연락처 보기