Li Yu, Lu Bing, Qiang Xinhua, Lin Yibin, He Jie, Cai Yunxiang
School of Medicine, Huzhou University, Huzhou, Zhejiang, 313000, People's Republic of China.
Department of Infectious Diseases, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, 313000, People's Republic of China.
Infect Drug Resist. 2025 Mar 19;18:1521-1537. doi: 10.2147/IDR.S507908. eCollection 2025.
Non-typhoidal (NTS) infections typically present as localized inflammation near the intestinal mucosal epithelium. However, some NTS strains can breach the intestinal barrier and enter the bloodstream, leading to bacteremia and severe systemic infections. The mechanisms by which NTS invades the bloodstream remain unclear.
In this study, we isolated 36 NTS strains from patients with diarrhea and bacteremia at First Affiliated Hospital of Huzhou University. Strains represented two distinct clinical manifestations, and were subjected to whole-genome sequencing, comparative genomics, and genetic differentiation analysis to identify genes potentially involved in bloodstream invasion. Additionally, we conducted inhibition assays using quercetin, a chemical inhibitor of the identified gene pathways, to validate our findings.
Our analysis revealed that genes distinguishing the bloodstream isolates from the fecal isolates were primarily involved in the AI-2 quorum sensing pathway and biofilm-associated protein transport. Subsequent biofilm formation assays demonstrated that the bloodstream isolates exhibited significantly higher biofilm formation capacity compared to the fecal isolates. Upon the addition of quercetin, biofilm formation was equally inhibited in both groups. Collectively, these findings suggest that genes involved in the AI-2 pathway and biofilm-associated protein transport may be key factors contributing to the development of bacteremia in NTS infections.
非伤寒型（NTS）感染通常表现为肠道黏膜上皮附近的局部炎症。然而，一些NTS菌株可突破肠道屏障进入血液，导致菌血症和严重的全身感染。NTS侵入血液的机制尚不清楚。
在本研究中，我们从湖州师范学院附属第一医院腹泻和菌血症患者中分离出36株NTS菌株。这些菌株代表两种不同的临床表现，并进行了全基因组测序、比较基因组学和遗传分化分析，以鉴定可能参与血液侵袭的基因。此外，我们使用槲皮素（一种已鉴定基因途径的化学抑制剂）进行抑制试验，以验证我们的发现。
我们的分析表明，区分血液分离株和粪便分离株的基因主要参与AI-2群体感应途径和生物膜相关蛋白转运。随后的生物膜形成试验表明，与粪便分离株相比，血液分离株表现出显著更高的生物膜形成能力。加入槲皮素后，两组的生物膜形成均受到同等程度的抑制。总体而言，这些发现表明，参与AI-2途径和生物膜相关蛋白转运的基因可能是导致NTS感染中菌血症发生的关键因素。
