Wojciech Krzysztof Jankowski
September 2018
During recent years, we have been witnessing the emergence of more and more antibiotic-resistant strains. Some of the mutants, such as the infamous New Delhistrain of Klebsiella pneumoniae, possess an incredibly broad spectrum of resistance to antibiotics, which poses a direct threat of not being able to treat infections of such microorganisms with currently available substances.
Therefore, a group of researchers from Genetech in San Francisco started developing new types of antibiotics based on modified arylomycins - lipooligopeptides with the ability to bind to the bacterial Type I signal peptidase, compromising the transport of proteins across the membrane and severely disrupting the bacterial metabolysm (1).
The original arylomycins, however, were not able to penetrate the cell wall of gram-negative bacteria, and were therefore effective only against certain gram-positives (2). The researchers from Genetech were able to overcome this problem by developing modified versions of the drug such as the so-called G0775 that are able to penetrate the wall of gram-negative bacteria (3). Since the arylomycin derivatives utilize a novel mechanism of action compared to other antibiotics families, they may find use in treating infections caused by highly resistant strains, such as the aforesaid New Delhi orPseudomonas aeruginosa.
Keywords: #microbiology #antibioticresistance #bacteria
(1) Tuteja R, Type I signal peptidase: an overview (Archives of biochemistry and biophysics, 2005)
(2) Shimana Jet al., Arylomycins A and B, New Biaryl-bridged Lipopeptide Antibiotics Produced by Streptomyces sp. Tue 6075. I. Taxonomy, Fermentation, Isolation and Biological Activities (The Journal of Antibiotics 55(6):565-70, July 2002)
(3) Smith P et al., Optimized arylomycins are a new class of Gram-negative antibiotics (Nature - International Journal of Science, September 2018)
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