{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zahid MSH"],"funding":["NIAID NIH HHS","National Institutes of Health"],"pagination":["fnab062"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8433491"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["368(11)"],"pubmed_abstract":["Host-directed therapies (HDTs) could enhance the activity of traditional antibiotics. AR-12 is a promising HDT against intracellular pathogens including Salmonella enterica serovar Typhimurium, and has been shown to act through modulation of autophagy and the Akt kinase pathway. Since AR-12 does not inhibit the growth of planktonic bacteria but only works in conjunction with the infected host-cell, we hypothesized that AR-12 could enhance the activity of antibiotics in less-susceptible strains in the intracellular host environment. We found that repetitive passaging of S. typhimurium in macrophages in the absence of antibiotics led to a 4-fold reduction in their intracellular susceptibility to streptomycin (STR), but had no effect on the bacteria's sensitivity to AR-12. Moreover, when the "],"journal":["FEMS microbiology letters"],"pubmed_title":["Overcoming reduced antibiotic susceptibility in intracellular Salmonella enterica serovar Typhimurium using AR-12."],"pmcid":["PMC8433491"],"funding_grant_id":["R01AI125147","R01 AI125147"],"pubmed_authors":["Ainslie KM","Johnson MM","Zahid MSH","Varma DM","Landavazo A","Bachelder EM","Blough BE"],"additional_accession":[]},"is_claimable":false,"name":"Overcoming reduced antibiotic susceptibility in intracellular Salmonella enterica serovar Typhimurium using AR-12.","description":"Host-directed therapies (HDTs) could enhance the activity of traditional antibiotics. AR-12 is a promising HDT against intracellular pathogens including Salmonella enterica serovar Typhimurium, and has been shown to act through modulation of autophagy and the Akt kinase pathway. Since AR-12 does not inhibit the growth of planktonic bacteria but only works in conjunction with the infected host-cell, we hypothesized that AR-12 could enhance the activity of antibiotics in less-susceptible strains in the intracellular host environment. We found that repetitive passaging of S. typhimurium in macrophages in the absence of antibiotics led to a 4-fold reduction in their intracellular susceptibility to streptomycin (STR), but had no effect on the bacteria's sensitivity to AR-12. Moreover, when the ","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jun","modification":"2025-04-19T18:18:57.025Z","creation":"2025-04-19T18:18:57.025Z"},"accession":"S-EPMC8433491","cross_references":{"pubmed":["34089315"],"doi":["10.1093/femsle/fnab062"]}}