Abstract
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.
Highlights
Streptococcus suis is an important pathogen associated with wide range of diseases in swine and human, including septicemia, pneumonia, endocarditis, meningitis, and arthritis (Lun et al 2007)
The activity of NZ2114 against S. suis was stronger compared to ampicillin (MIC 0.17–0.34 μM) (Table 1)
A decrease in S. suis CVCC606 of 1.28 and 1.83 lg CFU/ ml (>90% reduction) was observed within 3 h at one and two times of minimal inhibitory concentration (MIC), respectively. Those decreases were nearly equal to that obtained by ampicillin treatment (1.49 lg CFU/ml decrease) at two times of MIC (Fig. 1a), but NZ2114 failed to inhibit bacterial regrowth after 3 and 4 h of inoculate for 1× and 2 × MIC, respectively
Summary
Streptococcus suis is an important pathogen associated with wide range of diseases in swine and human, including septicemia, pneumonia, endocarditis, meningitis, and arthritis (Lun et al 2007). It was found that S. suis was the fourth most significant pathogen in the breeder and weaner site. S. suis can be transmitted to human beings by direct contact. The repeated intensive outbreaks of human S. suis infection have raised great public concern worldwide regarding S. suis as an emerging zoonotic pathogen. It is the most common cause of adult infection in Vietnam (Mai et al 2008) and the second most common in Thailand (Suankratay et al 2004). In Europe, the largest number of zoonotic infections due to S. suis, have
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