Zhao Chenfeng, Liu Pingjuan, Lin Xiaoshu, Wan Chenyu, Liao Kang, Guo Penghao, Deng Jiankai, Wu Zhongwen, Peng Yaqin, Huang Junqi, Chen Yili
Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Infection. 2025 Apr;53(2):667-678. doi: 10.1007/s15010-024-02456-x. Epub 2025 Feb 3.
The type VI secretion system (T6SS) has been recognized as a novel virulence factor in Klebsiella pneumoniae. This study investigated the occurrence of T6SS genes in carbapenem-resistant Klebsiella pneumoniae (CRKP) strains during intestinal colonization and evaluated their effect on the development of bloodstream infections.
The study encompassed 2,385 patients admitted to the intensive care unit (ICU) and subjected to routine screening for intestinal colonization with CRKP. PFGE was employed on CRKP strains isolated from both the patients' intestine and blood cultures, confirming their genetic similarity. PCR was employed to detect the presence of carbapenemase genes, T6SS genes, and virulence genes. Quantitative real-time PCR was conducted to assess the expression levels of the core genes associated with the T6SS. The correlation between T6SS expression and sBSI was further investigated.
Approximately 10% (238/2385) of ICU patients tested positive for CRKP colonization. Among patients who tested positive, 10.1% (24/238) developed CRKP-sBSI. Patients carrying T6SS-positive CRKP isolates were more commonly linked to a history of invasive procedures, antibiotic use, and immunosuppression (P < 0.05), and were strongly associated with 28-day mortality (P < 0.001). It indicated that T6SS-positive CRKP strains exhibited a higher prevalence of virulence genes, such as rmpA and iucA, compared to T6SS-negative ones (P < 0.001). Compared to the strains isolated from simple colonization group, there was a significant increase in the mRNA expression of both hcp and vgrG genes (P < 0.05) of strains from the sBSI group, suggesting the key genes of the T6SS may play a significant role in the occurrence and progression of sBSI caused by CRKP.
The presence of the T6SS in a CRKP strain from intestinal colonization can serve as a promising predictive marker for sBSI. Conducting screenings for CRKP in patients' intestinal flora and monitoring T6SS carriage can improve the prevention and management of CRKP bloodstream infections.
VI型分泌系统（T6SS）已被确认为肺炎克雷伯菌中的一种新型毒力因子。本研究调查了耐碳青霉烯类肺炎克雷伯菌（CRKP）菌株在肠道定植期间T6SS基因的发生情况，并评估了它们对血流感染发展的影响。
该研究纳入了2385名入住重症监护病房（ICU）并接受CRKP肠道定植常规筛查的患者。对从患者肠道和血培养中分离出的CRKP菌株进行脉冲场凝胶电泳（PFGE），确认它们的基因相似性。采用聚合酶链反应（PCR）检测碳青霉烯酶基因、T6SS基因和毒力基因的存在。进行定量实时PCR以评估与T6SS相关的核心基因的表达水平。进一步研究T6SS表达与严重血流感染（sBSI）之间的相关性。
约10%（238/2385）的ICU患者CRKP定植检测呈阳性。在检测呈阳性的患者中，10.1%（24/238）发生了CRKP-sBSI。携带T6SS阳性CRKP分离株的患者更常与侵入性操作史、抗生素使用和免疫抑制相关（P<0.05），并且与28天死亡率密切相关（P<0.001）。这表明与T6SS阴性的CRKP菌株相比，T6SS阳性的CRKP菌株毒力基因（如rmpA和iucA）的患病率更高（P<0.001）。与从单纯定植组分离出的菌株相比，sBSI组菌株的hcp和vgrG基因的mRNA表达均显著增加（P<0.05），这表明T6SS的关键基因可能在CRKP引起的sBSI的发生和发展中起重要作用。
肠道定植的CRKP菌株中T6SS的存在可作为sBSI的一个有前景的预测标志物。对患者肠道菌群中的CRKP进行筛查并监测T6SS携带情况可改善CRKP血流感染的预防和管理。
