A Mycobacterium ulcerans Toxin, Mycolactone, Causes Apoptosis in Guinea Pig Ulcers and Tissue Culture Cells

Author:

George Kathleen M.1,Pascopella Lisa1,Welty Diane M.1,Small P. L. C.1

Affiliation:

1. Microscopy Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana 59840

Abstract

ABSTRACT Mycobacterium ulcerans is the causative agent of Buruli ulcer, a tropical ulcerative skin disease. One of the most intriguing aspects of this disease is the presence of extensive tissue damage in the absence of an acute inflammatory response. We recently purified and characterized a macrolide toxin, mycolactone, from M. ulcerans . Injection of this molecule into guinea pig skin reproduced cell death and lack of acute inflammatory response similar to that seen following the injection of viable bacteria. We also showed that mycolactone causes a cytopathic effect on mouse fibroblast L929 cells that is characterized by cytoskeletal rearrangements and growth arrest within 48 h. However, these results could not account for the extensive cell death which occurs in Buruli ulcer. The results presented here demonstrate that L929 and J774 mouse macrophage cells die via apoptosis after 3 to 5 days of exposure to mycolactone. Treatment of cells with a pan-caspase inhibitor can inhibit mycolactone-induced apoptosis. We demonstrate that injection of mycolactone into guinea pig skin results in cell death via apoptosis and that the extent of apoptosis increases as the lesion progresses. These results may help to explain why tissue damage in Buruli ulcer is not accompanied by an acute inflammatory response.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

Reference32 articles.

1. Inhibition of human B lymphocyte cell cycle progression and differentiation by rapamycin;Aagaard-Tillery K. M.;Cell. Immunol.,1994

2. Differential activation of a calcium-dependent endonuclease in human B lymphocytes. Role in ionomycin-induced apoptosis;Aagaard-Tillery K. M.;J. Immunol.,1995

3. Erythromycin shortens neutrophil survival by accelerating apoptosis

4. Bryskier A. Agouridas C. Gasc J.-C. Classification of macrolide antibiotics Macrolides: chemistry pharmacology and clinical uses. Bryskier A. J. Butzler J.-P. Neu H. C. Tulkens P. M. 1993 5 66 Arnette S.A. Paris France

5. Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation;Cohen G. M.;Biochem. J.,1992

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3