Gilmer Daniel B, Schmitz Jonathan E, Thandar Mya, Euler Chad W, Fischetti Vincent A
Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, 1230 York Avenue, New York, New York, United States of America.
PLoS One. 2017 Jan 3;12(1):e0169180. doi: 10.1371/journal.pone.0169180. eCollection 2017.
Streptococcus suis infects pigs worldwide and may be zoonotically transmitted to humans with a mortality rate of up to 20%. S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to treat these pathogens using bacteriophage lysins. The bacteriophage lysin PlySs2 is derived from an S. suis phage and displays potent lytic activity against most strains of that species including serotypes 2 and 9. At 64 μg/ml, PlySs2 reduced multiple serotypes of S. suis by 5 to 6-logs within 1 hour in vitro and exhibited a minimum inhibitory concentration (MIC) of 32 μg/ml for a S. suis serotype 2 strain and 64 μg/ml for a serotype 9 strain. Using a single 0.1-mg dose, the colonizing S. suis serotype 9 strain was reduced from the murine intranasal mucosa by >4 logs; a 0.1-mg dose of gentamicin reduced S. suis by <3-logs. A combination of 0.05 mg PlySs2 + 0.05 mg gentamicin reduced S. suis by >5-logs. While resistance to gentamicin was induced after systematically increasing levels of gentamicin in an S. suis culture, the same protocol resulted in no observable resistance to PlySs2. Thus, PlySs2 has both broad and high killing activity against multiple serotypes and strains of S. suis, making it a possible tool in the control and prevention of S. suis infections in pigs and humans.
猪链球菌在全球范围内感染猪，并可能人畜共患地传播给人类，死亡率高达20%。已证明猪链球菌在体外对两种主要的首选药物青霉素和庆大霉素产生耐药性。因此，我们一直在寻求一种使用噬菌体溶素治疗这些病原体的替代疗法。噬菌体溶素PlySs2源自一种猪链球菌噬菌体，对该物种的大多数菌株，包括2型和9型血清型，都具有强大的裂解活性。在体外，PlySs2在64μg/ml时，1小时内可使多种血清型的猪链球菌减少5至6个对数，对一株猪链球菌2型菌株的最低抑菌浓度（MIC）为32μg/ml，对9型菌株为64μg/ml。使用单次0.1mg剂量，可使定殖于小鼠鼻内黏膜的猪链球菌9型菌株减少超过4个对数；0.1mg剂量的庆大霉素可使猪链球菌减少不到3个对数。0.05mg PlySs2 + 0.05mg庆大霉素的组合可使猪链球菌减少超过5个对数。虽然在猪链球菌培养物中系统性地提高庆大霉素水平后会诱导对庆大霉素的耐药性，但相同的方案并未导致对PlySs2产生可观察到的耐药性。因此，PlySs2对多种血清型和菌株的猪链球菌具有广泛且高效的杀伤活性，使其成为控制和预防猪和人类猪链球菌感染的一种可能工具。
