TY - JOUR
T1 - Targeting Lipoprotein Biogenesis
T2 - Considerations towards Antimicrobials
AU - El Arnaout, Toufic
AU - Soulimane, Tewfik
N1 - Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/8
Y1 - 2019/8
N2 - Decades have passed without approval of a new antibiotic class. Several companies have recently halted related discovery efforts because of multiple obstacles. One promising route under research is to target the lipoprotein maturation pathway in light of major recent findings and the virulence roles of lipoproteins. To support the future design of selective drugs, considerations and priority-setting are established for the main lipoprotein processing enzymes (Lgt, LspA, and Lnt) based on microbiology, biochemistry, structural biology, chemical design, and pharmacology. Although not all bacterial species will be similarly impacted by drug candidates, several advantages make LspA a top target to pursue in the development of novel antibiotics effective against bacteria that are resistant to existing drugs.
AB - Decades have passed without approval of a new antibiotic class. Several companies have recently halted related discovery efforts because of multiple obstacles. One promising route under research is to target the lipoprotein maturation pathway in light of major recent findings and the virulence roles of lipoproteins. To support the future design of selective drugs, considerations and priority-setting are established for the main lipoprotein processing enzymes (Lgt, LspA, and Lnt) based on microbiology, biochemistry, structural biology, chemical design, and pharmacology. Although not all bacterial species will be similarly impacted by drug candidates, several advantages make LspA a top target to pursue in the development of novel antibiotics effective against bacteria that are resistant to existing drugs.
KW - antibiotic resistance
KW - drug design
KW - lipid transferase
KW - lipoproteins
KW - signal peptidase
UR - http://www.scopus.com/inward/record.url?scp=85064648905&partnerID=8YFLogxK
U2 - 10.1016/j.tibs.2019.03.007
DO - 10.1016/j.tibs.2019.03.007
M3 - Review article
SN - 0968-0004
VL - 44
SP - 701
EP - 715
JO - Trends in Biochemical Sciences
JF - Trends in Biochemical Sciences
IS - 8
ER -