BACTERIOSTASIS OF ULINASTATIN INHIBITS THE GROWTH OF ESCHERICHIA COLI IN VITRO

Abstract

Intro: Ulinastatin is a broad-spectrum serine protease inhibitor that is isolated and purified from human urine, with strong anti-inflammatory and cytoprotective actions in various cell and animal models. Ulinastatin inhibits trypsin and is commonly used in the treatment of sepsis and pancreatitis by regulating the host immune system. However, it remains unclear whether ulinastatin has a direct antimicrobial activity. Herein, this study aims to determine the direct bacteriostasis of ulinastatin on Escherichia coli (E. coli). Methods: Growth curves of E. coli BL21(DE3) treated with gradient concentration of ulinastatin (high, median, and low dose) were conducted, with OD600 measured per 1 hour. Findings: The bacterial growth of E. coli BL21(DE3) cultured with high, median, and low dose ulinastatin exhibited a gradient time to reach stationary phase. The time taken to reach plateau was the longest in the high-dose group, followed by the medium-dose group, and the shortest in the low-dose group approximately equal to the blank control group (treated with isovolumetric PBS). In addition, at each measurement, the OD600 of the high-dose group was the lowest compared to other groups, with a lower OD600 of medium-dose group than that in the lowdose group where the value was adjacent to the blank control. These results suggested that the growth of E. coli might be restrained directly by ulinastatin. Conclusion: Ulinastatin could effectively inhibit the growth of E. coli in a dose effect relationship. Thus, our findings may provide new insights into the underlying mechanisms involved in effects of ulinastatin on the treatment of infectious diseases caused by bacteria in spite of further researches remaining to be performed at the molecular and cellular levels. (Acknowledgements: Grant from School of Public Health of Southern Medical University, China, No.GW202222 to H.C.)