title: Antibacterial and antivirulence effect of 6-N-hydroxylaminopurine in Listeria monocytogenes.
abstract: The emerging development of antibiotic resistant bacteria calls for novel types of antibacterial agents. In this work we examined the putative antibacterial effect of purine analogs in Listeria monocytogenes. We show that, among several tested purine analogs, only 6-N-hydroxylaminopurine (6-N-HAP) reduces the viability of the Gram-positive pathogen Listeria monocytogenes. As in Bacillus subtilis, 6-N-HAP terminates expression at guanine riboswitches in L. monocytogenes hence preventing expression of their downstream genes. However, we show that the bacteriocidal effect of the compound was unlinked to the terminated expression at the guanine riboswitches. When further examining the antimicrobial effect, we observed that 6-N-HAP acts as a potent mutagen in L. monocytogenes, by increasing the mutation rate and inducing the SOS-response. Also, addition of 6-N-HAP decreased virulence gene expression by reducing both the levels and activity of the virulence regulator PrfA.
authors.affiliation: Department of Molecular Biology, Umeå University, 90187 Umeå, Sweden.|Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden.|Umeå Centre for Microbial Research (UCMR), Umeå University, 90187 Umeå, Sweden.
authors.forename: Stefanie Sandra
authors.initials: SS
authors.lastname: Krajewski
authors.affiliation: Department of Molecular Biology, Umeå University, 90187 Umeå, Sweden.|Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden.|Umeå Centre for Microbial Research (UCMR), Umeå University, 90187 Umeå, Sweden.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Isoz
authors.affiliation: Department of Molecular Biology, Umeå University, 90187 Umeå, Sweden.|Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden.|Umeå Centre for Microbial Research (UCMR), Umeå University, 90187 Umeå, Sweden.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Johansson
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D008089:Listeria monocytogenes / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology*; D050296:Microbial Viability / Q000187:drug effects / Q000235:genetics; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D059645:Mutation Rate; D058928:Riboswitch / Q000187:drug effects; D012294:Rifamycins / Q000494:pharmacology; D013014:SOS Response, Genetics / Q000187:drug effects / Q000235:genetics; D014774:Virulence / Q000187:drug effects* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D009153:Mutagens; D058928:Riboswitch; D012294:Rifamycins; C032610:6-N-hydroxylaminopurine; D000225:Adenine