Multidrug resistance is one of the most urgent problems in clinical research. It particularly concerns the gram-negative
bacteria strains, which possess an outer membrane largely impermeable for small molecules.
Many microorganisms produce secondary natural products, the potential antibiotic
effects of which are extensively investigated. Scientists are continually
screening natural secondary products of various structural motifs to investigate their effects as possible antibiotics, which
could enter in the microorganism and possibly inhibit essential enzymes.
‘A class of quinone-like substances containing an additional epoxide functional group can kill problematic Salmonella pathogens, probably by interfering with their bacterial stress response system.’
German scientists have now examined a class of quinone-like substances
containing an additional epoxide functional group for their antibiotic activities. As they report in the journal
, the compounds can kill problematic Salmonella pathogens, probably by interfering with their
bacterial stress response system.
Stephan Sieber, Iris Antes and their colleagues at
Technical University of Munich were particularly interested in a class of molecules with a structural scaffold present in
various natural products. Its quinone-epoxide motif could be crucial for antibacterial bioactivity, they assumed.
The scientists used click chemistry to label the molecular
candidates with fluorescent dyes. Thus, in a proteomic
approach, their - at this point unknown - protein targets within the
microorganisms could be identified, once they interacted
with the candidates. One of the candidates called FM233 was not only
found to kill Salmonella, which is one of the
most problematic pathogens, but its target proteins were identified as
The scientists reported that two of the three proteins belonged to
cellular stress response machinery. "FM233 antibiotic activity stemmed
to a large extend from
downregulation of enzymatic stress response, and corresponding
sensitization of cells to stress," they wrote. "The
function of the third of the three targeted proteins had been unknown
before. However, after employing test systems on various possible
activities, the scientists concluded "that this protein is not involved
in the antibacterial mechanism of
The notion that FM233 can intervene in the bacterial stress response system could be a good starting point for further
research on the antibacterial activities of that particular molecular scaffold. As only small chemical changes can cause
strong responses, the battle against resistance is ongoing.