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Pathogenic mycobacteria are among the most devastating infectious agents of mortality worldwide causing tuberculosis, opportunistic infections of AIDS patients, and leprosy. A major problem in controlling mycobacterial infections is their remarkable antibiotic tolerance that limits chemotherapeutic options and is the root cause of treatment failure. In addition, pathogenic mycobacteria are able to persist for a long period of time inside the host cells circumventing host destruction. Persistence and antibiotic resistance are phenotypically associated and are supported by related genetic or physiological determinants.
We are studying mechanisms involved in intrinsic antibiotic resistance, persistence/virulence and how they are connected in pathogenic mycobacteria. Understanding these mechanisms may help develop novel antimycobacterial drugs that overcome the inherent antibiotic resistance and latent infection of pathogenic mycobacteria.
Selected Publications
Nguyen L and Thompson CJ. (2006) Foundations of antibiotic resistance in bacterial physiology: the mycobacterial paradigm. Trends Microbiol. 14, 304-312. [PubMed]
Houben EN, Nguyen L, Pieters J. (2006) Interaction of pathogenic mycobacteria with the host immune system. Curr Opin Microbiol. 9, 76-85. [PubMed]
Morris RP, Nguyen L, Gatfield J, Visconti K, Nguyen K, Schnappinger D, Ehrt S, Liu Y, Heifets L, Pieters J, Schoolnik G, Thompson CJ. (2005) Ancestral antibiotic resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 102, 12200-12205. [PubMed]
Nguyen L, Chinnapapagari S, Thompson CJ. (2005) FbpA-Dependent biosynthesis of trehalose dimycolate is required for the intrinsic multidrug resistance, cell wall structure, and colonial morphology of Mycobacterium smegmatis. J Bacteriol. 187, 6603-6611. [PubMed]
Nguyen L and Pieters J. (2005) The Trojan horse: survival tactics of pathogenic mycobacteria in macrophages. Trends Cell Biol. 15, 269-276. [PubMed]
*Walburger A, *Koul A, *Ferrari G, *Nguyen L, Prescianotto-Baschong C, Huygen K, Klebl B, Thompson C, Bacher G, Pieters J. (2004) Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Science. 304, 1800-1804. (* first authors) [PubMed]
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