Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Key Laboratory of Tumor Immunopathology, Youjiang Medical University for Nationalities, Baise, China.
Front Cell Infect Microbiol. 2024 Jul 18;14:1401462. doi: 10.3389/fcimb.2024.1401462. eCollection 2024.
Bacterial urinary tract infections (UTI) are among the most common infectious diseases worldwide. The rise of multidrug-resistant (MDR) uropathogenic (UPEC) UTI cases is a significant threat to healthcare systems. Several probiotic bacteria have been proposed as an alternative to combat MDR UTI. Lactic acid bacteria in the genus are some of the most studied and used probiotics. However, strain-specific effects play a critical role in probiotic properties. KUB-AC5 (AC5), isolated from the chicken gut, confers antimicrobial and immunobiotic effects against some human pathogens. However, the antibacterial and immune modulatory effects of AC5 on UPEC have never been explored.
Here, we investigated both the direct and indirect effects of AC5 against UPEC isolates (UTI89, CFT073, and clinical MDR UPEC AT31) . Using a spot-on lawn, agar-well diffusion, and competitive growth assays, we found that viable AC5 cells and cell-free components of this probiotic significantly reduced the UPEC growth of all strains tested. The human bladder epithelial cell line UM-UC-3 was used to assess the adhesion and pathogen-attachment inhibition properties of AC5 on UPEC.
Our data showed that AC5 can attach to UM-UC-3 and decrease UPEC attachment in a dose-dependent manner. Pretreatment of UPEC-infected murine macrophage RAW264.7 cells with viable AC5 (multiplicity of infection, MOI = 1) for 24 hours enhanced macrophage-killing activity and increased proinflammatory (, , and ) and anti-inflammatory () gene expression. These findings indicate the gut-derived AC5 probiotic could be a potential urogenital probiotic against MDR UTI.
细菌尿路感染(UTI)是全球最常见的传染病之一。多药耐药(MDR)尿路致病性大肠杆菌(UPEC)UTI 病例的增加对医疗保健系统构成了重大威胁。一些益生菌已被提议作为治疗 MDR UTI 的替代方法。属于乳酸杆菌属的益生菌是研究和使用最多的益生菌之一。然而,菌株特异性效应在益生菌特性中起着关键作用。从鸡肠道中分离出来的 KUB-AC5(AC5)对一些人类病原体具有抗菌和免疫生物作用。然而,AC5 对 UPEC 的抗菌和免疫调节作用从未被探索过。
在这里,我们研究了 AC5 对 UPEC 分离株(UTI89、CFT073 和临床 MDR UPEC AT31)的直接和间接影响。使用点样草坪、琼脂孔扩散和竞争生长测定,我们发现活的 AC5 细胞和该益生菌的无细胞成分显著降低了所有测试菌株的 UPEC 生长。人膀胱上皮细胞系 UM-UC-3 用于评估 AC5 对 UPEC 的粘附和病原体附着抑制特性。
我们的数据表明,AC5 可以附着在 UM-UC-3 上,并以剂量依赖的方式减少 UPEC 的附着。用活的 AC5(感染复数,MOI=1)预处理感染 UPEC 的鼠巨噬细胞 RAW264.7 细胞 24 小时,增强了巨噬细胞杀伤活性,并增加了促炎(、和)和抗炎()基因表达。这些发现表明,源自肠道的 AC5 益生菌可能是一种针对 MDR UTI 的潜在泌尿生殖道益生菌。