Guanosine enhances the bactericidal effect of cefotaxime sodium on Streptococcus suis by activating bacterial metabolism

Streptococcus suis (S. suis) is an important zoonotic pathogen, and the development of its antibiotic resistance has made the infections difficult to treat. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against multidrug-resistant bacteria. However, the mechanism by which metabolites act as antibiotic adjuvant remains unclear.

Here, we found that guanosine metabolism was repressed in multidrug-resistant S. suis. Exogenous guanosine promoted the antibacterial effects of ceftiofur sodium (CEF) in vitro and in vivo. Furthermore, we demonstrated that exogenous guanosine promoted the biosynthesis of purine pathway, TCA cycle and bacterial respiration, which make bacteria more sensitive to the killing effect of antibacterial.