In vitro antibacterial activity of MGDG-palmitoyl from Oscillatoria acuminata NTAPC05 against extended-spectrum β-lactamase producers

Extended-spectrum beta-lactamase (ESBL)-producing bacteria pose a big challenge in clinical practices, warranting a new therapeutic strategy. In this study, methanol extract of the marine cyanobacterium Oscillatoria acuminata NTAPC05 was fractionated under bioassay guidance and the fractions were tested against three well-characterized ESBL-producing bacteria Escherichia coli U655, Stenotrophomonas maltophilia B929 and Enterobacter asburiae B938. Out of the four HPLC fractions, fraction 2 showed bactericidal activity against all the three ESBL producers much more efficiently (MIC 100 mu g m1(-1)) than the fourth-generation cephalosporin (MIC >125 mu g m1(-1)). The active fraction was subjected to time-kill test at concentrations of 1/2 x MIC, 1 x MIC and 2 x MIC, and the results substantiated the bactericidal property of the fraction against the ESBL producers. Spectral analysis revealed monogalactosyldiacylglycerol containing a palmitoyl (MGDG-palmitoyl), being reported for the first time, as the active fraction, and its bactericidal property against ESBL producers was determined. The active fraction appears to damage the bacterial membrane leading to lysis of the cell, as revealed in confocal laser scanning microscopy (CLSM) analysis, that was confirmed in scanning electron microscopic analysis. Cytotoxicity assay revealed the 0. acuminata compound to be safe to a normal cell line HEK293 (human embryonic kidney cell). The in silico analysis of MGDG-palmitoyl revealed two successive H-bonding interactions with Leu198 of TEM1 beta-lactamase. Taken together, the MGDG-palmitoyl from 0. acuminata NTAPC05 offers potential to develop analogs as a therapeutic for bacteremia caused by ESBL producers.