Efficacy of the small molecule inhibitor of Lipid II BAS00127538 against Acinetobacter baumannii

Abstract

ObjectiveTo test the activity of a small molecule compound that targets Lipid II against Acinetobacter baumannii.MethodsSusceptibility to small molecule Lipid II inhibitor BAS00127538 was assessed using carbapenem- and colistin-resistant clinical isolates of A. baumannii. In addition, synergy between colisitin and this compound was assessed.ResultsSmall molecule Lipid II inhibitor BAS00127538 potently acts against A. baumannii and acts synergistically with colistin.ConclusionFor the first time, a compound that targets Lipid II is described that acts against multi-drug resistant isolates of A. baumannii. The synergy with colistin warrants further lead development of BAS00127538.

OmpW is a potential target for eliciting protective immunity against Acinetobacter baumannii infections

“…Currently, the reported non-antibiotic strategies for controlling A. baumannii infections include antisense peptide nucleic acids [5], lytic bacteriophages [6], small molecule inhibitors [7][8][9][10][11], and immunological interventions [12][13][14][15][16][17][18][19][20][21][22]. In previous studies, immunization with outer membrane vesicles (OMVs) generated strong protective immunity against A. baumannii infections [16,17].…”

Structure–activity exploration of a small-molecule Lipid II inhibitor

“… 16 In particular, BAS00127538 showed activity against S. aureus (MIC 0.5), irrespective of vancomycin- or methicillin resistance. BAS00127538 was also active against the Gram-negative bacteria E. coli and A. baumannii , 35 with MICs of 8 μg/mL and 2 μg/mL, respectively. The antibacterial activity of ASN10791182, 4400-0093, 56133428, and BAS00127537 was significantly reduced as compared to that of BAS00127538, in particular against S. aureus and A. baumannii ( Table S2 ).…”

Characterization of Rv0888, a Novel Extracellular Nuclease from Mycobacterium tuberculosis

“…Interestingly, Rv0888 activity was inhibited by four Chinese medicine monomers (Oleuropein, 6-Gingerol, Corylifolinin, and Acteoside). Previous studies have concentrated on small molecule inhibitors, focusing on proteins and factors related to the biosynthesis of pathogens: limiting S. aureus entry into endothelial cells by structural analogs of ML 141 24 ; blocking coronavirus and filovirus entry into host cells by the cysteine protease inhibitor K11777 25 ; blocking phosphatidylglycerol-LtaS binding and inhibiting LTA synthesis in ItaS-expressin S. aureus and in Escherichia coli with compound 1771 26 ; Inhibiting A. baumannii Lipid II (an essential precursor of cell wall biosynthesis) through the use of BAS00127538 27 . Subsequent drug studies then shifted to cell wall proteins and proteases: small molecule inhibitors of sortase that act as an anti-infective therapy against hospital-acquired S. aureus infection without the side effects of standard antibiotics 28 ; tetrahydrolipstatin that inhibits the phospholipase/thioesterase (Rv3802c) of M. tuberculosis 29 ; an inhibitor of mPTPB (a virulence factor of tuberculosis) which was acquired by organocatalysis 30 ; six small molecules that were confirmed to act as novel EndA (surface endonuclease of the S. pneumoniae ) inhibitors 31 .…”