Increased survival and proliferation of the epidemic strain Mycobacterium abscessus subsp massiliense CRM0019 in alveolar epithelial cells

Increased survival and proliferation of the epidemic strain Mycobacterium abscessus subsp massiliense CRM0019 in alveolar epithelial cells

Author Ribeiro, Giovanni Monteiro Autor UNIFESP Google Scholar
Matsumoto, Cristianne Kayoko Autor UNIFESP Google Scholar
Real, Fernando Autor UNIFESP Google Scholar
Teixeira, Daniela Autor UNIFESP Google Scholar
Duarte, Rafael Silva Google Scholar
Mortara, Renato Arruda Autor UNIFESP Google Scholar
Leao, Sylvia Cardoso Autor UNIFESP Google Scholar
Carvalho-Wodarz, Cristiane de Souza Autor UNIFESP Google Scholar
Abstract Background: Outbreaks of infections caused by rapidly growing mycobacteria have been reported worldwide generally associated with medical procedures. Mycobacterium abscessus subsp. massiliense CRM0019 was obtained during an epidemic of postsurgical infections and was characterized by increased persistence in vivo. To better understand the successful survival strategies of this microorganism, we evaluated its infectivity and proliferation in macrophages (RAW and BMDM) and alveolar epithelial cells (A549). For that, we assessed the following parameters, for both M. abscessus CRM0019 as well as the reference strain M. abscessus ATCC 19977: internalization, intracellular survival for up 3 days, competence to subvert lysosome fusion and the intracellular survival after cell reinfection. Results: CRM0019 and ATCC 19977 strains showed the same internalization rate (approximately 30% after 6 h infection), in both A549 and RAW cells. However, colony forming units data showed that CRM0019 survived better in A549 cells than the ATCC 19977 strain. Phagosomal characteristics of CRM0019 showed the bacteria inside tight phagosomes in A549 cells, contrasting to the loosely phagosomal membrane in macrophages. This observation holds for the ATCC 19977 strain in both cell types. The competence to subvert lysosome fusion was assessed by acidification and acquisition of lysosomal protein. For M. abscessus strains the phagosomes were acidified in all cell lines

nevertheless, the acquisition of lysosomal protein was reduced by CRM0019 compared to the ATCC 19977 strain, in A549 cells. Conversely, in macrophages, both M. abscessus strains were located in mature phagosomes, however without bacterial death. Once recovered from macrophages M. abscessus could establish a new intracellular infection. Nevertheless, only CRM0019 showed a higher growth rate in A549, increasing nearly 10- fold after 48 and 72 h. Conclusion: M. abscessus CRM0019 creates a protective and replicative niche in alveolar epithelial cells mainly by avoiding phagosome maturation. Once recovered from infected macrophages, CRM0019 remains infective and displays greater intracellular growth in A549 cells compared to the ATCC 19977 strain. This evasion strategy in alveolar epithelial cells may contribute to the long survival of the CRM0019 strain in the host and thus to the inefficacy of in vivo treatment.
Keywords Mycobacterium abscessus
Phagosome
Acidification
A549
Macrophages
CRM0019
xmlui.dri2xhtml.METS-1.0.item-coverage London
Language English
Sponsor Sao Paulo Research Foundation (FAPESP)
Grant number FAPESP: 2012/04913-8
FAPESP: 2013/16018-6
FAPESP: 2009/14665-9
Date 2017
Published in Bmc Microbiology. London, v. 17, p. -, 2017.
ISSN 1471-2180 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent -
Origin http://dx.doi.org/10.1186/s12866-017-1102-7
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000410951100002
URI https://repositorio.unifesp.br/handle/11600/57360

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