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Identification of Virulence Markers of Mycobacterium abscessus for Intracellular Replication in Phagocytes
Published on: September 27, 2018
Analysing nonsynonymous mutations between two Mycobacterium bovis strains with contrasting pathogenic profiles
Mercedes Bigi1, Cristina Lourdes Vazquez2, Ana Beatriz C Castelão3
1Universidad de Buenos Aires, Facultad de Agronomía, Cátedra de Microbiología Agrícola, INBA-CONICET, Buenos Aires, Argentina.
Two Mycobacterium bovis strains in Argentina show genetic differences impacting virulence. Strain 04-303 is highly lethal, while strain 534 has reduced phthiocerol dimycocerosate synthesis, affecting its survival in bovine macrophages.
Area of Science:
- Veterinary Microbiology
- Infectious Diseases
- Genomics
Background:
- Mycobacterium bovis causes bovine tuberculosis, a significant zoonotic disease with economic impact.
- Two distinct M. bovis strains, 04-303 (wild boar) and 534 (cattle), were isolated in Argentina.
- Previous studies indicated differential virulence, with 04-303 causing 100% mortality in mice versus survival with limited damage for 534.
Purpose of the Study:
- To compare predictive proteins encoded in the genomes of M. bovis strains 04-303 and 534.
- To identify polymorphic proteins and their potential roles in virulence differences between the strains.
- To investigate the impact of genetic variations on phthiocerol dimycocerosate (PDIM) synthesis and bacterial survival.
Main Methods:
- Comparative genomic analysis of M. bovis strains 04-303 and 534.
- Identification and characterization of polymorphic proteins, focusing on virulence factors.
- Experimental investigation of PDIM synthesis and its correlation with bacterial behavior in macrophages.
Main Results:
- 141 polymorphic proteins were identified between the two M. bovis strains.
- Nine virulence proteins were polymorphic in strain 04-303, and five in strain 534.
- Significant polymorphisms in PDIM synthesis/transport proteins were observed, with mutations in strain 534 impacting PDIM levels and macrophage survival.
Conclusions:
- Strain-specific genetic variations, particularly in PDIM-related proteins, contribute to differential virulence of M. bovis.
- Reduced PDIM synthesis in strain 534 correlates with impaired replication and survival in bovine macrophages.
- Understanding these molecular differences is crucial for developing novel vaccines and diagnostics for bovine tuberculosis.
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