Spontaneous Healing of Mycobacterium ulcerans Lesions in the Guinea Pig Model
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Citações na Scopus
15
Tipo de produção
article
Data de publicação
2015
Editora
PUBLIC LIBRARY SCIENCE
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Autores
SILVA-GOMES, Rita
MARCQ, Elly
TRIGO, Gabriela
GONCALVES, Carine M.
CASTRO, Antonio G.
PEDROSA, Jorge
FRAGA, Alexandra G.
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Citação
PLOS NEGLECTED TROPICAL DISEASES, v.9, n.12, article ID e0004265, 12p, 2015
Resumo
Buruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans infection. BU is characterized by a wide range of clinical forms, including non-ulcerative cutaneous lesions that can evolve into severe ulcers if left untreated. Nevertheless, spontaneous healing has been reported to occur, although knowledge on this process is scarce both in naturally infected humans and experimental models of infection. Animal models are useful since they mimic different spectrums of human BU disease and have the potential to elucidate the pathogenic/protective pathway(s) involved in disease/healing. In this time-lapsed study, we characterized the guinea pig, an animal model of resistance to M. ulcerans, focusing on the macroscopic, microbiological and histological evolution throughout the entire experimental infectious process. Subcutaneous infection of guinea pigs with a virulent strain of M. ulcerans led to early localized swelling, which evolved into small well defined ulcers. These macroscopic observations correlated with the presence of necrosis, acute inflammatory infiltrate and an abundant bacterial load. By the end of the infectious process when ulcerative lesions healed, M. ulcerans viability decreased and the subcutaneous tissue organization returned to its normal state after a process of continuous healing characterized by tissue granulation and reepethelialization. In conclusion, we show that the experimental M. ulcerans infection of the guinea pig mimics the process of spontaneous healing described in BU patients, displaying the potential to uncover correlates of protection against BU, which can ultimately contribute to the development of new prophylactic and therapeutic strategies.
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Referências
- George KM, 1999, SCIENCE, V283, P854, DOI 10.1126/science.283.5403.854
- KRIEG RE, 1974, ARCH DERMATOL, V110, P783, DOI 10.1001/archderm.110.5.783
- O'Brien C, 2013, AUST VET J, V91, P296, DOI 10.1111/avj.12071
- Tanghe A, 2007, INFECT IMMUN, V75, P2642, DOI 10.1128/IAI.01622-06
- Marsollier L, 2003, INT J ANTIMICROB AG, V22, P562, DOI 10.1016/S0924-8579(03)00240-1
- Torrado E, 2007, INFECT IMMUN, V75, P977, DOI 10.1128/IAI.00889-06
- Bentoucha A, 2001, ANTIMICROB AGENTS CH, V45, P3109, DOI 10.1128/AAC.45.11.3109-3112.2001
- READ JK, 1974, INFECT IMMUN, V9, P1114
- Coutanceau E, 2007, J EXP MED, V204, P1395, DOI 10.1084/jem.20070234
- REVILL WDL, 1973, LANCET, V2, P873
- Silva MT, 2009, LANCET INFECT DIS, V9, P699, DOI 10.1016/S1473-3099(09)70234-8
- Oliveira MS, 2005, INFECT IMMUN, V73, P6299, DOI 10.1128/IAI.73.10.6299-6310.2005
- Torrado E, 2007, INFECT IMMUN, V75, P3979, DOI 10.1128/IAI.00290-07
- Dega H, 2000, ANTIMICROB AGENTS CH, V44, P2367, DOI 10.1128/AAC.44.9.2367-2372.2000
- MACCALLUM P, 1948, J PATHOL BACTERIOL, V60, P93, DOI 10.1002/path.1700600111
- Dega H, 2002, ANTIMICROB AGENTS CH, V46, P3193, DOI 10.1128/AAC.46.10.3193-3196.2002
- Hong H, 2005, CHEMBIOCHEM, V6, P643, DOI 10.1002/cbic.200400339
- Fraga AG, 2011, INFECT IMMUN, V79, P421, DOI 10.1128/IAI.00820-10
- Walsh DS, 2008, T ROY SOC TROP MED H, V102, P969, DOI 10.1016/j.trstmh.2008.06.006
- Tanghe A, 2001, INFECT IMMUN, V69, P5403, DOI 10.1128/IAI.69.9.5403-5411.2001
- Ellen DE, 2003, TROP MED INT HEALTH, V8, P90, DOI 10.1046/j.1365-3156.2003.00976.x
- Coutanceau E, 2006, MICROBES INFECT, V8, P2075, DOI 10.1016/j.micinf.2006.03.009
- Huygen K, 2009, MED MICROBIOL IMMUN, V198, P69, DOI 10.1007/s00430-009-0109-6
- George KM, 2000, INFECT IMMUN, V68, P877, DOI 10.1128/IAI.68.2.877-883.2000
- Torrado E, 2010, J IMMUNOL, V184, P947, DOI 10.4049/jimmunol.0902717
- Bolz M, 2014, PLOS NEGLECT TROP D, V8, DOI 10.1371/journal.pntd.0002968
- Carson C, 2014, PLOS NEGLECT TROP D, V8, DOI 10.1371/journal.pntd.0002668
- Connor DH, 1966, ARCH PATH, V81, P17
- Fraga AG, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0033406
- Fyfe JAM, 2010, PLOS NEGLECT TROP D, V4, DOI 10.1371/journal.pntd.0000791
- Gama JB, 2014, PLOS NEGLECT TROP D, V8, DOI 10.1371/journal.pntd.0003066
- Gordon CL, 2011, PLOS NEGLECT TROP D, V5, DOI 10.1371/journal.pntd.0001290
- Lagarrigue V, 2000, Med Trop (Mars), V60, P262
- Martins TG, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0032740
- O'Brien CR, 2014, PLOS NEGLECT TROP D, V8, DOI 10.1371/journal.pntd.0002666
- Portaels F, 2003, B SEANC ACAD R SCI O, V49, P30
- Tanghe A, 2008, PLOS NEGLECT TROP D, V2, DOI 10.1371/journal.pntd.0000199
- Walsh DS, 2007, AM J TROP MED HYG, V76, P132
- World Health Organization, 2004, WHOCDSCPEGBUI200410