Bacterial glycoproteins are frequently linked to pathogenesis and contain distinctive glycans that are absent from humans. We set out to develop an antibiotic strategy based on unique glycans present on pathogenic bacteria. In this study, metabolic labeling of bacterial glycans with azide-containing sugars allowed selective delivery of phosphine warheads to azide-covered Helicobacter pylori (Hp). We established that Hp's surface glycans are labeled by treatment with the metabolic substrate peracetylated N-azidoacetylglucosamine. We further demonstrated that azide-covered Hp react with phosphines conjugated to the immunostimulant dinitrophenyl (DNP), a compound capable of directing a host immune response against these cells. These data set the stage for further development of this glycosylation-based therapeutic strategy to eradicate Hp infection. Broadly, this work introduces a new paradigm for the development of antibiotics that target bacteria based on their unique glycans.

Chemical approach to target bacterial pathogens based on their unique glycans

243rd National Meeting (2012)

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