Tackling Antibiotic Resistance: Exploring 5-Fluorouracil as a Promising Antimicrobial Strategy for the Treatment of Streptococcus suis Infection.
Jing ZuoYingying QuanJinpeng LiYue LiDong SongXing-Ping LiYuxin WangLi YiYang WangPublished in: Animals : an open access journal from MDPI (2024)
Streptococcus suis ( S. suis ) is a zoonotic pathogen with a global distribution, which causes serious diseases in both humans and animals and economic losses in the swine industry. As antibiotic resistance increases, there is an urgent imperative to explore novel antibacterial alternatives. In the present study, we selected the anticancer drug 5-fluorouracil (5-FU) approved by the Food and Drug Administration (FDA) as a candidate drug to treat S. suis infections. The results showed that various pathogens, especially S. suis , are more sensitive to 5-FU. Moreover, the cytotoxicity of 5-FU is relatively low. Extensive in vitro assays demonstrated the pronounced bacteriostatic and bactericidal efficacy of 5-FU against susceptible and multidrug-resistant S. suis strains. Its mechanisms of action include damage to the bacterial cell walls and membranes, resulting in the leakage of intracellular components, and the inhibition of thymidylate synthase (TS), leading to a depletion of deoxythymidine triphosphate (dTTP) pools, ultimately causing thymine-less death and lethal DNA damage in bacteria. Gene-knockout experiments further showed that 5-FU played a role by inhibiting the thyA gene-encoding thymidine synthase. Finally, we determined that S. suis infections can be alleviated by 5-FU in the mouse infection model. This study emphasizes the antibacterial potential of 5-FU against S. suis and provides evidence for its targeting of bacterial membrane damage and DNA damage. In summary, 5-FU can control S. suis infection and is expected to become a new alternative to antibiotics.
Keyphrases
- dna damage
- oxidative stress
- multidrug resistant
- drug administration
- stem cells
- escherichia coli
- emergency department
- candida albicans
- biofilm formation
- gram negative
- staphylococcus aureus
- dna repair
- gene expression
- pseudomonas aeruginosa
- genome wide
- cystic fibrosis
- risk assessment
- drug resistant
- copy number
- drug induced
- mesenchymal stem cells
- human health
- drug delivery
- reactive oxygen species
- silver nanoparticles
- cell therapy
- dna methylation
- bone marrow
- smoking cessation
- adverse drug
- genome wide identification