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Mechanisms of drug resistance: daptomycin resistance
Author(s) -
Tran Truc T.,
Munita Jose M.,
Arias Cesar A.
Publication year - 2015
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12948
Subject(s) - daptomycin , biology , cell envelope , microbiology and biotechnology , lipopeptide , antibiotic resistance , lipid ii , bacillus subtilis , bacteria , multidrug tolerance , drug resistance , gram positive bacteria , antimicrobial , bacterial cell structure , antibiotics , staphylococcus aureus , genetics , biofilm , vancomycin , escherichia coli , gene
Daptomycin (DAP) is a cyclic lipopeptide with in vitro activity against a variety of Gram‐positive pathogens, including multidrug‐resistant organisms. Since its introduction into clinical practice in 2003, DAP has become an important key frontline antibiotic for severe or deep‐seated infections caused by Gram‐positive organisms. Unfortunately, DAP resistance (DAP‐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‐R 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 provided 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.