{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zang Z"],"funding":["Key Technologies Research and Development Program","Robert J Kleberg Jr and Helen C Kleberg Foundation","NCATS NIH HHS","NIAID NIH HHS","Camille and Henry Dreyfus Foundation Inc","National Institutes of Health","NIGMS NIH HHS","National Science Foundation","Australian Research Council"],"pagination":["263-277.e11"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12866962"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["34(2)"],"pubmed_abstract":["The rise of antibiotic resistance motivates a revived interest in phage therapy. However, bacteria possess dozens of anti-phage immune systems that confer resistance to therapeutic phages. Chemical inhibitors of these anti-phage immune systems could be employed as adjuvants to overcome resistance in phage-based therapies. Here, we report a class of chemical inhibitors that selectively inhibit type II Thoeris anti-phage immune systems from diverse bacteria-including antibiotic-resistant pathogens, thereby sensitizing phage-resistant bacteria to phages. These inhibitors block the biosynthesis of a histidine-ADPR intracellular \"alarm\" signal by ThsB, thereby preventing ThsA from arresting phage replication. Chemical inhibition of the Thoeris defense improves the efficacy of a model phage therapy against a phage-resistant clinical isolate of P. aeruginosa in a mouse infection, suggesting a therapeutic potential. These findings demonstrate that the selective inhibition of anti-phage defense systems can improve the efficacy of therapeutic phages, suggesting a strategy to circumvent phage-therapy resistance."],"journal":["Cell host & microbe"],"pubmed_title":["Chemical inhibition of a bacterial immune system."],"pmcid":["PMC12866962"],"funding_grant_id":["TL1 TR002531","R01 AI141479","R35 GM138376"],"pubmed_authors":["Fedorova I","Zang Z","Zhu Y","Gerdt JP","Miraj G","Angus SP","Le S","Deng J","Arya G","Ve T","Sabonis D","Shi Y","Dixon SAH","Tamulaitiene G","Duncan OK","Liang H","Cai Y","Pepin RH","Zhang C","Duerkop BA","Bondy-Denomy J"],"additional_accession":[]},"is_claimable":false,"name":"Chemical inhibition of a bacterial immune system.","description":"The rise of antibiotic resistance motivates a revived interest in phage therapy. However, bacteria possess dozens of anti-phage immune systems that confer resistance to therapeutic phages. Chemical inhibitors of these anti-phage immune systems could be employed as adjuvants to overcome resistance in phage-based therapies. Here, we report a class of chemical inhibitors that selectively inhibit type II Thoeris anti-phage immune systems from diverse bacteria-including antibiotic-resistant pathogens, thereby sensitizing phage-resistant bacteria to phages. These inhibitors block the biosynthesis of a histidine-ADPR intracellular \"alarm\" signal by ThsB, thereby preventing ThsA from arresting phage replication. Chemical inhibition of the Thoeris defense improves the efficacy of a model phage therapy against a phage-resistant clinical isolate of P. aeruginosa in a mouse infection, suggesting a therapeutic potential. These findings demonstrate that the selective inhibition of anti-phage defense systems can improve the efficacy of therapeutic phages, suggesting a strategy to circumvent phage-therapy resistance.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-04T03:20:49.693Z","creation":"2026-07-04T03:12:01.699Z"},"accession":"S-EPMC12866962","cross_references":{"pubmed":["41619738"],"doi":["10.1016/j.chom.2026.01.003"]}}