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Mycobacterium abscessus morphotype comparison in a murine model.

Lindsay J Caverly1, Silvia M Caceres2, Cori Fratelli3

  • 1Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, United States of America.

Plos One
|February 13, 2015
PubMed
Summary

The rough morphotype of Mycobacterium abscessus (M. abscessus) causes a stronger inflammatory response in the lungs than the smooth morphotype. This finding is important for understanding M. abscessus lung infections, especially in cystic fibrosis patients.

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Area of Science:

  • Medical Microbiology
  • Immunology
  • Pulmonary Medicine

Background:

  • Pulmonary infections with Mycobacterium abscessus (M. abscessus) are a growing concern, particularly for individuals with lung conditions like cystic fibrosis.
  • M. abscessus exhibits two distinct morphotypes: smooth and rough, but their differential impact on disease virulence remains poorly understood.

Purpose of the Study:

  • To investigate the distinct host inflammatory responses elicited by smooth versus rough morphotypes of M. abscessus in a pulmonary infection model.
  • To compare the virulence and host response of M. abscessus smooth and rough morphotypes in immunocompetent and cystic fibrosis mouse models.

Main Methods:

  • Development of an immune-competent mouse model for pulmonary M. abscessus infection using intratracheal inoculation with M. abscessus in fibrin plugs.
  • Analysis of lung and splenic tissues, bronchoalveolar lavage fluid (BALF) for bacterial load, leukocyte counts, differentials, and cytokine expression at 3 and 14 days post-inoculation.
  • Monitoring for spontaneous in vivo morphotype conversion from smooth to rough M. abscessus and assessing associated host responses, including weight loss.

Main Results:

  • Pulmonary M. abscessus infection was established and predominantly localized in the lungs with minimal systemic spread in the fibrin plug model.
  • The rough morphotype of M. abscessus induced significantly higher neutrophil levels in BALF compared to the smooth morphotype at 14 days post-inoculation in both wild-type and cystic fibrosis mice.
  • In vivo conversion from smooth to rough M. abscessus morphotype was observed in 21% of mice, correlating with a trend towards greater weight loss.

Conclusions:

  • The M. abscessus rough morphotype elicits a more pronounced pulmonary inflammatory response, characterized by increased neutrophils, compared to the smooth morphotype.
  • The fibrin plug model effectively establishes localized pulmonary M. abscessus infection, allowing for the study of morphotype-specific host-pathogen interactions.
  • Understanding morphotype-specific virulence is crucial for developing targeted therapeutic strategies against M. abscessus lung infections, especially in vulnerable populations such as cystic fibrosis patients.