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Chemical Structure| 39031-44-2 Chemical Structure| 39031-44-2

Structure of 39031-44-2

Chemical Structure| 39031-44-2

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Zang, Zhiyu ; Duncan, Olivia K ; Sabonis, Dziugas ; Shi, Yun ; Miraj, Gause ; Fedorova, Iana , et al.

Abstract: The rise of antibiotic resistance motivates a revived interest in phage therapy. However, bacteria possess dozens of anti-bacteriophage 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 that anti-phage systems can be selectively inhibited by small molecules, thereby sensitizing phage-resistant bacteria to phages. We discovered a class of chemical inhibitors that inhibit the type II Thoeris anti-phage immune system. These inhibitors block the biosynthesis of a histidine-ADPR intracellular ‘alarm’ signal by ThsB and prevent ThsA from arresting phage replication. These inhibitors promiscuously inhibit type II Thoeris systems from diverse bacteria—including antibiotic-resistant pathogens. Chemical inhibition of the Thoeris defense improved the efficacy of a model phage therapy against a phage-resistant strain of P. aeruginosa in a mouse infection, suggesting a therapeutic potential. Furthermore, these inhibitors may be employed as chemical tools to dissect the importance of the Thoeris system for phage defense in natural microbial communities.

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Product Details of [ 39031-44-2 ]

CAS No. :39031-44-2
Formula : C8H7N3O
M.W : 161.16
SMILES Code : O=C(C1=CN2C=CC=CC2=N1)N
MDL No. :MFCD11643701
InChI Key :BEHYAANJUKYBTH-UHFFFAOYSA-N
Pubchem ID :13126094

Safety of [ 39031-44-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501
 

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