Distinct molecular characteristics and virulence profiles of carbapenem-resistant Acinetobacter baumannii, Escherichia coli, and Enterobacter cloacae isolated from patients with inborn errors of immunity

TL;DR

This study finds that drug-resistant bacteria from patients with immune disorders have unique genetic traits and reduced virulence, suggesting the immune environment influences bacterial evolution.

Contribution

The first study to compare molecular and virulence profiles of carbapenem-resistant bacteria in patients with inborn errors of immunity versus non-IEI patients.

Findings

CR-AB from IEI patients showed more diverse carbapenemase genes compared to non-IEI patients.

CR-ECO and CR-ECL from IEI patients had reduced carriage of virulence-related genes like adherence and nutritional/metabolic factors.

The fimA gene in CR-ECO was the only statistically significant difference observed between IEI and non-IEI groups.

Abstract

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 Acinetobacter baumannii (CR-AB), carbapenem-resistant Escherichia coli (CR-ECO), and carbapenem-resistant Enterobacter cloacae (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 blaOXA-23, followed by ST109 (blaOXA-58, 9.1%) and ST70 (blaNDM-1, 9.1%), whereas all CR-ABs in the non-IEI group were ST2 with blaOXA-23. CR-ECL strains from the IEI group harbored blaKPC-2 (14.3%) and blaVIM-1 (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 fimA gene in CR-ECO (P < 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 Acinetobacter baumannii (CR-AB), Escherichia coli (CR-ECO), and Enterobacter cloacae (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.

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