Next Article in Journal
Colonization of Dogs and Their Owners with Staphylococcus aureus and Staphylococcus pseudintermedius in Households, Veterinary Practices, and Healthcare Facilities
Previous Article in Journal
Customized Minimally Invasive Protocols for the Clinical and Microbiological Management of the Oral Microbiota
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Microorganisms
Volume 10
Issue 4
10.3390/microorganisms10040673
microorganisms-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Mycobacterium bovis PknG R242P Mutation Results in Structural Changes with Enhanced Virulence in the Mouse Model of Infection

by
Fábio Muniz de Oliveira
1,2,
Victor Oliveira Procopio
1,
Gabriela de Lima Menezes
3,
Roosevelt Alves da Silva
3,
André Kipnis
1 and
Ana Paula Junqueira-Kipnis
1,*
1
Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiania 74605-050, Brazil
2
Department of Biomedical Sciences, Faculdade Estácio de Sá de Goiás—FESGO, Goiania 74063-010, Brazil
3
Biosystem Collaborative Nucleus, Federal University of Jataí, Jatai 75804-020, Brazil
*
Author to whom correspondence should be addressed.
Microorganisms 2022, 10(4), 673; https://doi.org/10.3390/microorganisms10040673
Submission received: 22 February 2022 / Revised: 14 March 2022 / Accepted: 16 March 2022 / Published: 22 March 2022
(This article belongs to the Topic Infectious Diseases)
Browse Figures
Versions Notes

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. bovispknG 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.
Keywords: molecular dynamics; pathogenicity; macrophages; virulence; neutrophils; SNP; protein kinase molecular dynamics; pathogenicity; macrophages; virulence; neutrophils; SNP; protein kinase
Graphical Abstract

Share and Cite

MDPI and ACS Style

Oliveira, F.M.d.; Procopio, V.O.; de Lima Menezes, G.; Silva, R.A.d.; Kipnis, A.; Junqueira-Kipnis, A.P. Mycobacterium bovis PknG R242P Mutation Results in Structural Changes with Enhanced Virulence in the Mouse Model of Infection. Microorganisms 2022, 10, 673. https://doi.org/10.3390/microorganisms10040673

AMA Style

Oliveira FMd, Procopio VO, de Lima Menezes G, Silva RAd, Kipnis A, Junqueira-Kipnis AP. Mycobacterium bovis PknG R242P Mutation Results in Structural Changes with Enhanced Virulence in the Mouse Model of Infection. Microorganisms. 2022; 10(4):673. https://doi.org/10.3390/microorganisms10040673

Chicago/Turabian Style

Oliveira, Fábio Muniz de, Victor Oliveira Procopio, Gabriela de Lima Menezes, Roosevelt Alves da Silva, André Kipnis, and Ana Paula Junqueira-Kipnis. 2022. "Mycobacterium bovis PknG R242P Mutation Results in Structural Changes with Enhanced Virulence in the Mouse Model of Infection" Microorganisms 10, no. 4: 673. https://doi.org/10.3390/microorganisms10040673

APA Style

Oliveira, F. M. d., Procopio, V. O., de Lima Menezes, G., Silva, R. A. d., Kipnis, A., & Junqueira-Kipnis, A. P. (2022). Mycobacterium bovis PknG R242P Mutation Results in Structural Changes with Enhanced Virulence in the Mouse Model of Infection. Microorganisms, 10(4), 673. https://doi.org/10.3390/microorganisms10040673

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop