In vitro and in vivo antibacterial effect of NZ2114 against Streptococcus suis type 2 infection in mice peritonitis models

Jian Jiao, Ruoyu Mao, Da Teng, Xiumin Wang, Ya Hao, Na Yang, Xiao Wang, Xingjun Feng, Jianhua Wang

NZ2114 is a promising candidate for therapeutic application owing to potent activity to gram-positive bacterium such as Streptococcus pneumoniae and Staphylococcus aureus. This work is the first report to describe the in vitro and in vivo antibacterial characteristics of NZ2114 against Streptococcus suis. It exhibited strong antimicrobial activity against S. suis type 2 strains CVCC 606, CVCC 3309, and CVCC 3928 at a low minimal inhibitory concentration (MIC) of 0.03-0.06 μM. The NZ2114 killed over 99.9% of tested S. suis CVCC 606 in Mueller-Hinton medium within 4 h when treated with 4 × MIC. It caused only less than 0.25% hemolytic activity in the concentration of 256 μg/ml. Additionally, NZ2114 exhibited potent in vivo activity to S. suis. All mice were survival when the dosage was low to 0.2 mg/kg. Over 99% of S. suis cells were killed within 4 h in blood, lung, liver and spleen with dosage of 10, 20, and 40 mg/kg in mice peritonitis models and no pathogen were detected after 24 h of treatment. Further, no pathological phenomenon in lung and low level of inflammatory cytokines in blood were detected. These results indicate that NZ2114 has the potential to be a new antimicrobial agent candidate for the clinical treatment of infection caused by S. suis type 2.