Chemotherapy-Associated Changes of Histopathological Features of Mycobacterium ulcerans Lesions in a Buruli Ulcer Mouse Model Marie-Thérèse Ruf a , b , Daniela Schütte a , b , Aurélie Chauffour c , Vincent Jarlier c , Baohong Ji c , † and Gerd Pluschke a , b a Swiss Tropical and Public Health Institute, Basel, Switzerland b University of Basel, Basel, Switzerland c UPMC Université Paris 06, ER5, EA 1541, Laboratoire de Bactériologie-Hygiène, Paris, France ABSTRACT Combination chemotherapy with rifampin and streptomycin (RIF-STR) for 8 weeks is currently recommended by the WHO as the first-line treatment for Mycobacterium ulcerans infection (Buruli ulcer). To gain better insight into the mode of action of these antibiotics against established M. ulcerans infection foci and to characterize recovery of local immune responses during chemotherapy, we conducted a detailed histopathological study of M. ulcerans -infected and RIF-STR-treated mice. Mice were inoculated with M. ulcerans in the footpad and 11 weeks later treated with RIF-STR. Development of lesions during the first 11 weeks after infection and subsequent differences in disease progression between RIF-STR-treated and untreated mice were studied. Changes in histopathological features, footpad swelling, and number of CFU were analyzed. After inoculation with M. ulcerans , massive infiltrates dominated by polymorphonuclear leukocytes developed at the inoculation site but did not prevent bacterial multiplication. Huge clusters of extracellular bacteria located in large necrotic areas and surrounded by dead leukocytes developed in the untreated mice. Chemotherapy with RIF-STR led to a rapid drop in CFU associated with loss of solid Ziehl-Neelsen staining of acid-fast bacilli. Development of B-lymphocyte clusters and of macrophage accumulations surrounding the mycobacteria demonstrated the resolution of local immune suppression. Results demonstrate that the experimental M. ulcerans mouse infection model will be a valuable tool to investigate efficacy of new treatment regimens and of candidate vaccines.
Chemotherapy-Associated Changes of Histopathological Features of Mycobacterium ulcerans Lesions in a Buruli Ulcer Mouse Model
Abstract
Chemotherapy-Associated Changes of Histopathological Features of Mycobacterium ulcerans Lesions in a Buruli Ulcer Mouse Model Marie-Thérèse Ruf a , b , Daniela Schütte a , b , Aurélie Chauffour c , Vincent Jarlier c , Baohong Ji c , † and Gerd Pluschke a , b a Swiss Tropical and Public Health Institute, Basel, Switzerland b University of Basel, Basel, Switzerland c UPMC Université Paris 06, ER5, EA 1541, Laboratoire de Bactériologie-Hygiène, Paris, France ABSTRACT Combination chemotherapy with rifampin and streptomycin (RIF-STR) for 8 weeks is currently recommended by the WHO as the first-line treatment for Mycobacterium ulcerans infection (Buruli ulcer). To gain better insight into the mode of action of these antibiotics against established M. ulcerans infection foci and to characterize recovery of local immune responses during chemotherapy, we conducted a detailed histopathological study of M. ulcerans -infected and RIF-STR-treated mice. Mice were inoculated with M. ulcerans in the footpad and 11 weeks later treated with RIF-STR. Development of lesions during the first 11 weeks after infection and subsequent differences in disease progression between RIF-STR-treated and untreated mice were studied. Changes in histopathological features, footpad swelling, and number of CFU were analyzed. After inoculation with M. ulcerans , massive infiltrates dominated by polymorphonuclear leukocytes developed at the inoculation site but did not prevent bacterial multiplication. Huge clusters of extracellular bacteria located in large necrotic areas and surrounded by dead leukocytes developed in the untreated mice. Chemotherapy with RIF-STR led to a rapid drop in CFU associated with loss of solid Ziehl-Neelsen staining of acid-fast bacilli. Development of B-lymphocyte clusters and of macrophage accumulations surrounding the mycobacteria demonstrated the resolution of local immune suppression. Results demonstrate that the experimental M. ulcerans mouse infection model will be a valuable tool to investigate efficacy of new treatment regimens and of candidate vaccines.Preview Only. This article cannot be rented because we do not currently have permission from the publisher.
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Chemotherapy-Associated Changes of Histopathological Features of Mycobacterium ulcerans Lesions in a Buruli Ulcer Mouse Model
Ruf, Marie-Thérèse; Schütte, Daniela; Chauffour, Aurélie; Jarlier, Vincent; Ji, Baohong; Pluschke, Gerd
Follow Antimicrobial Agents and Chemotherapy
, Volume 56 (2): 687
American Society For Microbiology – Feb 1, 2012
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