Mycobacterium fortuitum fabG4 knockdown studies: Implication as pellicle and biofilm specific drug target.
FabG4
Mycobacterium fortuitum
biofilm
drug target
pellicle
Journal
Journal of basic microbiology
ISSN: 1521-4028
Titre abrégé: J Basic Microbiol
Pays: Germany
ID NLM: 8503885
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
revised:
25
05
2022
received:
20
04
2022
accepted:
11
06
2022
pubmed:
24
6
2022
medline:
7
12
2022
entrez:
23
6
2022
Statut:
ppublish
Résumé
The fatty acid biosynthesis pathway is crucial for the formation of the mycobacterial cell envelope. The fatty acid synthase type-II (FAS-II) components are attractive targets for designing anti-biofilm inhibitors. Literature review, bioinformatics analysis, cloning, and sequencing led to the identification of a novel Mycobacterium fortuitum FAS-II gene MFfabG4 which interacts with mycobacterial proteins involved in biofilm formation. A manually curated M. fortuitum fatty acid biosynthesis pathway has been proposed exploiting functional studies from the Kyoto Encyclopedia of Genes and Genomes and Mycobrowser databases for MFFabG4. M. fortuitum MFfabG4 knockdown strain (FA) was constructed and validated by quantitative polymerase chain reaction. The FA strain displayed unstructured smooth colony architecture, correlating with decreased pathogenicity and virulence. MFfabG4 knockdown resulted in diminished pellicle and attenuated biofilm formation, along with impaired sliding motility, and reduced cell sedimentation. The FA strain showed lowered cell surface hydrophobicity, indicating attenuation in M. fortuitum intracellular infection-causing ability. Stress survival studies showed the requirement of MFfabG4 for survival in a nutrient-starved environment. The results indicate that MFfabG4 maintains the physiology of the cell envelope and is required for the formation of M. fortuitum pellicle and biofilm. The study corroborates the role of MFfabG4 as a pellicle- and biofilm-specific drug target and a potential diagnostic marker for M. fortuitum and related pathogenic mycobacteria.
Identifiants
pubmed: 35736669
doi: 10.1002/jobm.202200230
doi:
Substances chimiques
Fatty Acids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1504-1513Informations de copyright
© 2022 Wiley-VCH GmbH.
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