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Cpn60.1/GroEL-1/Hsp60-1, a New Potential Antimycobacterial Drug Target Involved in Antibiotics Resistance.

Bifani, Juan Pablo and Lefèvre, Philippe and Wang, Xiao-Ming and Karine, Soetaert and Rens, Céline and De Bruyn, Jacqueline and Lanéelle, Marie-Antoinette and Houyoux, Nicolas and Laval, Françoise and Lemassu, Anne and Wattiez, Ruddy and Daffé, Mamadou and Fontaine, Véronique (2011) Cpn60.1/GroEL-1/Hsp60-1, a New Potential Antimycobacterial Drug Target Involved in Antibiotics Resistance. Microbiology, 157 (4). pp. 1205-1219. ISSN 1608-3237; 0026-2617

Abstract

The phenolic glycolipids (PGL) and the related phthiocerol and phthiodolone dimycocerosates (PDIM) are known to be essential for Mycobacterium tuberculosis infection in human tuberculosis. By studying a mutant M. bovis BCG strain, Δcpn60.1, unable to express Hsp60-1/GroEL-1/Cpn60-1 mycobacterial chaperone, we discovered that not only this strain is PDIM and PGL negative, but is also very sensitive to glycopeptide antibiotics. Proteins and RNA analyses allowed identifying a defect in the PpsA-E proteins expression. Proteomic analysis further suggested that other proteins, namely FadD26 and DrrA, involved in PDIM biosynthesis and transport, respectively, could also be reduced. Furthermore, the association of drugs targeting the cell wall biosynthesis and glycopeptides can synergistically inhibit multi-drug-resistant and extremely resistant strains. Overall, our study firstly emphasized the potential of Cpn60-1, or PpsE targeting drugs and puts glycopeptides in a good position in the pipeline of potential antibiotics to fight against tuberculosis.

Item Type: Article
Additional Information: No Intelectual property
Keywords: Mycobacterium tuberculosis; Hsp60/GroEL/Cpn60 mycobacterial chaperone; phthiocerol and phthiodolone dimycocerosates (PDIM) and the phenolic glycolipids (PGL); novel drug targets.
Date Deposited: 12 Oct 2016 00:45
Last Modified: 12 Oct 2016 00:45
URI: https://oak.novartis.com/id/eprint/10786

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