Tylosin (Tylosin A)

Tylosin (Tylosin A) is a veterinary macrolide antibiotic produced by Streptomyces fradiae, which exhibits high efficacy against Gram-positive bacteria^[1,2]. Tylosin is commonly used as a feed additive to promote animal growth and is also used in research on diseases such as bacterial diarrhea, pneumonia, and middle ear infections in poultry, swine, and cattle^[3,4].

In vitro, Tylosin (0.06-128µg/mL) was tested against 112 Staphylococcus aureus and 110 coagulase-negative Staphylococcus (CoNS) isolates using the broth microdilution method. The minimum inhibitory concentration (MIC) of Tylosin for both bacterial populations showed a bimodal distribution. Among them, 19 isolates (11 S. aureus and 8 CoNS) exhibited Tylosin MIC of ≥256µg/mL and showed no zones of inhibition around the 30µg Tylosin disk^[5]. In LPS (1µg/mL)-induced murine RAW264.7 macrophages, treatment with Tylosin (10 and 20µg/mL) for 18h dose-dependently inhibited the generation of nitric oxide (NO) and prostaglandin E₂ (PGE₂), and significantly reduced the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)^[6].

In vivo, oral administration of Tylosin (17.5mg/kg; q12h; 7 days) to healthy dogs resulted in a significant decrease in fecal microbial diversity by day 7, accompanied by a reduction in anaerobic bacteria such as Fusobacteriaceae and Veillonellaceae^[7]. In Balb/C mice, co-administration of Tylosin (10, 100, and 500mg/kg; s.c.) with LPS (250µg; i.p.) suppressed the LPS-induced elevation of serum pro-inflammatory cytokines (TNF-α and IL-1β) and increased the level of the anti-inflammatory cytokine IL-10 at the 2h time point across all tested doses^[8].

References:
[1] MCGUIRE J M, BONIECE W S, HIGGENS C E, et al. Tylosin, a new antibiotic: I. Microbiological studies[J], 1961.
[2] GIGUÈRE S, PRESCOTT J F, BAGGOT J D, et al. Antimicrobial therapy in veterinary medicine[M]. John Wiley & Sons, 2013.
[3] CAZER C L, ELDERMIRE E R, LHERMIE G, et al. The effect of tylosin on antimicrobial resistance in beef cattle enteric bacteria: A systematic review and meta-analysis[J]. Preventive Veterinary Medicine, 2020, 176: 104934.
[4] ČULIĆ O, ERAKOVIĆ V, PARNHAM M J. Anti-inflammatory effects of macrolide antibiotics[J]. European Journal of Pharmacology, 2001, 429(1-3): 209-229.
[5] ENTORF M, FEßLER A T, KADLEC K, et al. Tylosin susceptibility of staphylococci from bovine mastitis[J]. Veterinary Microbiology, 2014, 171(3-4): 368-373.
[6] CAO X Y, DONG M, SHEN J Z, et al. Tilmicosin and tylosin have anti-inflammatory properties via modulation of COX-2 and iNOS gene expression and production of cytokines in LPS-induced macrophages and monocytes[J]. International Journal of Antimicrobial Agents, 2006, 27(5): 431-438.
[7] MANCHESTER A C, WEBB C B, BLAKE A B, et al. Long-term impact of tylosin on fecal microbiota and fecal bile acids of healthy dogs[J]. Journal of Veterinary Internal Medicine, 2019, 33(6): 2605-2617.
[8] ER A, YAZAR E, UNEY K, et al. Effects of tylosin on serum cytokine levels in healthy and lipopolysaccharide-treated mice[J]. Acta Veterinaria Hungarica, 2010, 58(1): 75-81.

Tylosin (Tylosin A)是一种产自Streptomyces fradiae，且对革兰氏阳性菌有高效抗菌活性的兽医用大环内酯类抗生素^[1,2]。Tylosin通常用做促进动物生长的饲料添加剂，也用于家禽、猪和牛细菌性痢疾、肺炎和中耳感染等疾病的研究^[3,4]。

在体外，Tylosin（0.06-128μg/mL）通过肉汤微量稀释法处理112株Staphylococcus aureus和110株coagulase-negative Staphylococcus (CoNS)，两种菌群的Tylosin最低抑菌浓度（MIC）呈双峰分布，其中19株菌（11株S. aureus和8株CoNS）Tylosin的MIC ≥ 256μg/mL，且对30μg Tylosin纸片无抑菌圈^[5]。Tylosin（10, 20μg/mL）处理经脂多糖LPS（1μg/mL）诱导的小鼠RAW264.7巨噬细胞18h，能剂量依赖性地抑制一氧化氮（NO）和前列腺素E₂（PGE₂）的产生，并显著降低诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的蛋白表达^[6]。

在体内，Tylosin（17.5mg/kg; q12h; 7 days）通过口服给予健康犬，导致第7天粪便微生物多样性显著下降，并伴随Fusobacteriaceae和 Veillonellaceae等厌氧菌的减少^[7]。Tylosin（10, 100, and 500mg/kg; s.c.）与LPS（250μg; i.p.）同时处理Balb/C小鼠，2h后所有测试剂量下均能降低LPS引起的小鼠血清促炎细胞因子TNF-α和IL-1β水平的升高，并提高抗炎细胞因子IL-10的水平^[8]。