Mycobacterium bovis PknG R242P mutation results in structural changes with enhanced virulence in the mouse model of infection
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2022
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Abstract: Mycobacterium bovis is the causative agent of tuberculosis in domestic and wild animal
species and sometimes in humans, presenting variable degrees of pathogenicity. It is known that
PknG is involved in the first steps of Mycobacterium tuberculosis macrophage infection and immune
evasion. We questioned whether M. bovis pknG genes were conserved among mycobacteria and
if natural genetic modifications would affect its virulence. We discovered a single mutation at a
catalytic domain (R242P) of one M. bovis isolate and established the relation between the presence
of R242P mutation and enhanced M. bovis virulence. Here, we demonstrated that R242P mutation
alters the PknG protein conformation to a more open ATP binding site cleft. It was observed that
M. bovis with PknG mutation resulted in increased growth under stress conditions. In addition,
infected macrophages by M. bovis (R242P) presented a higher bacterial load compared with M. bovis
without the pknG mutation. Furthermore, using the mouse model of infection, animals infected with
M. bovis (R242P) had a massive innate immune response migration to the lung that culminated with
pneumonia, necrosis, and higher mortality. The PknG protein single point mutation in its catalytic
domain did not reduce the bacterial fitness but rather increased its virulence.
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Molecular dynamics, Pathogenicity, Macrophages, Virulence, Neutrophils, SNP, Protein kinase
Citação
OLIVEIRA, Fábio Muniz de et al. Mycobacterium bovis PknG R242P mutation results in structural changes with enhanced virulence in the mouse model of infection. Microorganisms, Basel, v. 10, n. 4, e673, 2022. DOI: 10.3390/microorganisms10040673. Disponível em: https://pubmed.ncbi.nlm.nih.gov/35456728/. Acesso em: 20 ago. 2024.