Shanmughan Prasanth, Subrahmaniyan Pravin, Bhatnagar Dhruv, Ranganathan Srinithi, Lele Pushkar P
Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas, USA.
Department of Biomedical Engineering, Medical College of Wisconsin and Marquette University, Milwaukee, Wisconsin, USA.
Biotechnol Bioeng. 2025 Feb;122(2):405-414. doi: 10.1002/bit.28870. Epub 2024 Nov 3.
Helicobacter pylori cells undergo chemotaxis toward several small molecules, called chemo-attractants, including urea produced by the epithelial cells of the stomach. The biophysical mechanisms of chemotaxis are not well understood in H. pylori. Here, we developed point sources of urea by encapsulating it in Poly(lactic-co-glycolic acid) or PLGA microbeads for H. pylori chemotaxis studies. Microscopy and Dynamic Light Scattering characterization indicated that the PLGA particles had an average diameter of < 0.8 μm. The particles were relatively stable and had a net negative surface charge. Absorbance measurements indicated that the beads released ~70% of the urea over a 2-week period, with most of the release occurring within the first 24-h period. Varying pH (2.0-7.0) had little effect on the rate of urea release. A diffusion model predicted that such beads could generate sufficient urea gradients to chemotactically attract H. pylori cells. Single-bead single-cell chemotaxis assays confirmed the predictions, revealing that H. pylori continued to be attracted to beads even after most of the urea had been released in the first 24 h. Our work highlights a novel use of PLGA microbeads as delivery vehicles for stimulating a chemotaxis response in H. pylori, with potential applications in bacterial eradication strategies.
幽门螺杆菌细胞会朝着几种小分子进行趋化运动，这些小分子被称为化学引诱剂，包括胃上皮细胞产生的尿素。幽门螺杆菌趋化作用的生物物理机制尚未完全了解。在此，我们通过将尿素封装在聚乳酸-乙醇酸共聚物（PLGA）微珠中来开发尿素点源，用于幽门螺杆菌趋化研究。显微镜和动态光散射表征表明，PLGA颗粒的平均直径小于0.8μm。这些颗粒相对稳定，表面带净负电荷。吸光度测量表明，微珠在2周内释放了约70%的尿素，大部分释放在最初的24小时内发生。不同的pH值（2.0 - 7.0）对尿素释放速率影响很小。一个扩散模型预测，这样的微珠可以产生足够的尿素梯度，以趋化性吸引幽门螺杆菌细胞。单珠单细胞趋化试验证实了这些预测，表明即使在最初24小时内大部分尿素已经释放后，幽门螺杆菌仍继续被微珠吸引。我们的工作突出了PLGA微珠作为刺激幽门螺杆菌趋化反应的递送载体的新用途，在细菌根除策略中具有潜在应用。
