Mechanisms of drug resistance: daptomycin resistance
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Fecha
2015
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Publicado en
Annals of the New York Academy of Sciences, 0077-8923, Vol. 1354, Nro. 32, 2015, p. 1-33
Publicado por
Wiley-Blackwell
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Resumen
Descripción
Abstract
Daptomycin (DAP) is a cyclic lipopeptide with in vitro activity against a variety of Gram-positive pathogens, including multidrug-resistant organisms. Since its introduction in clinical practice in 2003, DAP has become an important key front-line antibiotic for severe or deep-seated infections caused by Gram-positive organisms. Unfortunately, DAP-resistance (R) has been extensively documented in clinically important organisms such as Staphylococcus aureus, Enterococcus spp, and Streptococcus spp. Studies on the mechanisms of DAP-R in Bacillus subtilis and other Gram-positive bacteria indicate that the genetic pathways of DAP resistance are diverse and complex. However, a common phenomenon emerging from these mechanistic studies is that DAP-R is associated with important adaptive changes in cell wall and cell membrane homeostasis with critical changes in cell physiology. Findings related to these adaptive changes have offered novel insights into the genetics and molecular mechanisms of bacterial cell envelope stress response and the manner in which Gram-positive bacteria cope with the antimicrobial peptide attack and protect vital structures of the cell envelope such as the cell membrane. In this review, we will examine the most recent findings related to the molecular mechanisms of resistance to DAP in relevant Gram-positive pathogens and discuss the clinical implications for therapy against these important bacteria.
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Keywords
Daptomycin resistance, Bacillus subtilis, Staphylococcus aureus, Enterococcus
Temáticas
Homeostasis
Gram-positivos
Enterococcus
Gram-positivos
Enterococcus