Zhu Xiaodan, Fu Pan, Yang Songzhen, Wang Wenjie, Ying Wenjing, Sun Bijun, Sun Jinqiao, Wang Chuanqing, Zhou Qinhua, Wang Xiaochuan
Department of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Department of Clinical Microbiology Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Microbiol Spectr. 2025 Aug 5;13(8):e0028125. doi: 10.1128/spectrum.00281-25. Epub 2025 Jun 12.
Bacterial infections, especially multidrug-resistant Gram-negative bacterial infections, pose a great threat to patients with inborn errors of immunity (IEIs). This study investigates the molecular and virulence profiles of carbapenem-resistant (CR-AB), carbapenem-resistant (CR-ECO), and carbapenem-resistant (CR-ECL) strains from patients with IEI. Strains from IEI and non-IEI groups underwent antimicrobial susceptibility testing and whole-genome sequencing (NovaSeq 6000 PE150), with statistical analysis of differences. A total of 24 CR-AB, 17 CR-ECO, and 16 CR-ECL strains were included. Most CR-AB strains in the IEI group belonged to ST2 (81.8%), all harbored , followed by ST109 (, 9.1%) and ST70 (, 9.1%), whereas all CR-ABs in the non-IEI group were ST2 with . CR-ECL strains from the IEI group harbored (14.3%) and (14.3%), in contrast to the non-IEI group. Compared to the non-IEI group, strains in the IEI group exhibited lower carriage of immune modulation genes in CR-AB (18.2%-45.5% vs. 40.0%-80.0%), reduced carriage of adherence genes (50.0%-62.5% vs. 88.9%-100.0%) and nutritional/metabolic factor genes (25.0% vs. 55.6%) in CR-ECO, and lower carriage of nutritional/metabolic factor genes (28.6% vs. 50.0%) in CR-ECL. No statistically significant differences were observed between the groups, except for the gene in CR-ECO ( < 0.05). The distinct molecular characteristics and reduced virulence gene carriage were observed in CR-AB, CR-ECO, and CR-ECL isolates from patients with IEI, with greater carbapenemase gene diversity in CR-AB and CR-ECL. These findings emphasize the need for enhanced surveillance and tailored antimicrobial strategies in IEI populations.
Bacterial infection, especially drug-resistant bacterial infection, poses a great risk to patients with IEIs. Antimicrobial resistance, particularly in pediatric patients, is a growing global health threat. Bacteria undergo a series of adaptive changes in response to pressures from the host. Patients with IEI provide a unique immune environment that may profoundly influence the molecular characteristics of bacterial pathogens. However, little is known about the molecular and virulence profiles of carbapenem-resistant (CR-AB), (CR-ECO), and (CR-ECL) isolated from patients with IEI. This study, the first of its kind, shows that CR-AB, CR-ECO, and CR-ECL from patients with IEI have distinct molecular profiles, including reduced virulence gene carriage and more diverse carbapenemase genes. It highlights the role of host immune status in shaping pathogen evolution and resistance, emphasizing the importance of monitoring the adaptive variation of these bacteria in patients with IEI.
细菌感染，尤其是多重耐药革兰氏阴性菌感染，对先天性免疫缺陷（IEIs）患者构成巨大威胁。本研究调查了来自IEI患者的耐碳青霉烯类（CR-AB）、耐碳青霉烯类（CR-ECO）和耐碳青霉烯类（CR-ECL）菌株的分子和毒力特征。对IEI组和非IEI组的菌株进行了药敏试验和全基因组测序（NovaSeq 6000 PE150），并对差异进行了统计分析。共纳入24株CR-AB、17株CR-ECO和16株CR-ECL菌株。IEI组中的大多数CR-AB菌株属于ST2（81.8%），均携带……，其次是ST109（……，9.1%）和ST70（……，9.1%），而非IEI组中的所有CR-AB均为ST2且携带……。与非IEI组相比，IEI组中的CR-AB菌株免疫调节基因携带率较低（18.2%-45.5%对40.0%-80.0%），CR-ECO中黏附基因（50.0%-62.5%对88.9%-100.0%）和营养/代谢因子基因（25.0%对55.6%）的携带率降低，CR-ECL中营养/代谢因子基因的携带率较低（28.6%对50.0%）。除CR-ECO中的……基因外，两组之间未观察到统计学上的显著差异（P<0.05）。在来自IEI患者的CR-AB、CR-ECO和CR-ECL分离株中观察到了独特的分子特征和毒力基因携带率降低的情况，CR-AB和CR-ECL中的碳青霉烯酶基因多样性更高。这些发现强调了在IEI人群中加强监测和制定针对性抗菌策略的必要性。
细菌感染，尤其是耐药细菌感染，对IEIs患者构成巨大风险。抗菌药物耐药性，尤其是在儿科患者中，是全球日益严重 的健康威胁。细菌会因宿主压力而发生一系列适应性变化。IEI患者提供了独特的免疫环境，可能会深刻影响细菌病原体的分子特征。然而，对于从IEI患者中分离出的耐碳青霉烯类（CR-AB）、（CR-ECO）和（CR-ECL）的分子和毒力特征知之甚少。本研究首次表明，来自IEI患者的CR-AB、CR-ECO和CR-ECL具有不同的分子特征，包括毒力基因携带率降低和碳青霉烯酶基因更多样化。它突出了宿主免疫状态在塑造病原体进化和耐药性方面的作用，强调了监测IEI患者中这些细菌适应性变异的重要性。
