Identification and characterization of a novel prophage lysin against Streptococcus dysgalactiae

Streptococcus dysgalactiae infection could cause bovine mastitis and lead to huge economic losses to dairy industry. The abuse of antibiotics has resulted in growing drug-resistance of S. dysgalactiae that cause hard-to-treat infections. Bacteriophage lysin, as a novel antibacterial agent, has great potential for application against drug-resistant gram-positive bacteria. However, few studies have been conducted on the prophage lysin of S. dysgalactiae. In this study, we mined a novel prophage lysin, named Lys1644, from a clinical S. dysgalactiae isolate, by genome sequencing and bioinformatic analysis. Lys1644 was expressed and purified, and the lytic activity, antibacterial spectrum, optimal pH and temperature, lytic activity in milk, synergistic bacteriostasis with antibiotics was assessed. The Lys1644 prophage lysin showed high bacteriolysis activity specifically on S. dysgalactiae, which results in CFU 100-fold reduction in milk. Moreover, Lys1644 maintained high activity over a wide pH range (pH 5–10) and a wide temperature range (4–42 ℃). Synergistic bacteriostatic experiments showed that the combination of low dose Lys1644 (50 μg/mL) and subinhibitory concentration of aminoglycoside antibiotics (kanamycin or spectinomycin) can completely inhibit bacterial growth, suggesting that the combination of Lys1644 and antibiotics could be an effective therapeutic strategy against S. dysgalactiae infection.