1887

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Volume 157, Issue 4

Deletion of the gene in the glycopeptidolipid biosynthetic pathway results in loss of surface colonization capability, but enhanced ability to replicate in human macrophages and stimulate their innate immune response Free

Abstract

is considered to be the most virulent of the rapidly growing mycobacteria. Generation of bacterial gene knockout mutants has been a useful tool for studying factors that contribute to virulence of pathogenic bacteria. Until recently, the optimal genetic approach to generation of gene knockout mutants was not clear. Based on the recent identification of genetic recombineering as the preferred approach, a mutant was generated in which the gene , critical to glycopeptidolipid synthesis, was deleted. Compared to the previously well-characterized parental strain 390S, the deletion mutant had lost sliding motility and the ability to form biofilm, but acquired the ability to replicate in human macrophages and stimulate macrophage Toll-like receptor 2. This study demonstrates that deletion of a gene associated with expression of a cell-wall lipid can result in acquisition of an immunostimulatory, invasive bacterial phenotype and has important implications for the study of pathogenesis at the cellular level.

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Keyword(s): GPL, glycopeptidolipid , MBC, mimimum bactericidal concentration , MDM, monocyte-derived macrophage , NHS, normal human serum , NTM, non-tuberculous mycobacterium/mycobacteria , PIM, phosphatidyl-myo-inositol mannoside , TLR2, Toll-like receptor 2 and TNF, tumour necrosis factor
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2011-04-01
2024-04-19
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Deletion of the mmpL4b gene in the Mycobacterium abscessus glycopeptidolipid biosynthetic pathway results in loss of surface colonization capability, but enhanced ability to replicate in human macrophages and stimulate their innate immune response
Microbiology 157, 1187 (2011); https://doi.org/10.1099/mic.0.046557-0
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