Whole genome comparisons reveal gut-to-lung translocation of Escherichia coli and Burkholderia cenocepacia in two cases of ventilator-associated pneumonia in ICU patients.
Background: Identifying the sources of pathogenic bacteria causing ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients is crucial for developing effective prevention and treatment strategies. However, the scarcity of reported cases with confirmed sources limits the ability to evaluate and manage VAP, which remains a major challenge for healthcare systems globally.
Methods: Pathogens were isolated from endotracheal aspirate (ETA) samples of VAP patients using conventional culture techniques. Whole-genome comparisons, based on average nucleotide identity (ANI), were performed to identify genetically identical strains by comparing pulmonary isolate genomes with gut metagenome-derived bacterial genomes. Mouse models of pneumonia and colitis were used to validate the translocation of pathogenic bacteria from the gut to the lungs. Metagenomic analysis was performed to characterize the gut microbiome and resistome.
Results: Pathogenic isolates were obtained from the ETA samples of seven VAP patients, with one isolate per sample. Among these, Escherichia coli (Ec1) and Burkholderia cenocepacia (Bc1) from two patients were genetically identical to strains in their respective gut microbiota, with ANI values above 99%, indicating gut-to-lung translocation. The Ec1 strain demonstrated increased resistance to cefazolin while remaining susceptible to gentamicin, amikacin, and kanamycin, compared to previously reported pneumonia-associated E. coli strains. The Bc1 strain showed elevated resistance to macrolides, chloramphenicols, and tetracyclines relative to pneumonia-associated B. cenocepacia strains. Metagenomic analysis revealed a highly individualized gut microbiota composition among VAP patients. Notably, the translocated bacteria were not dominant within their gut microbiota. Additionally, these patients showed a marked increase in the total abundance of antibiotic resistance genes (ARGs) in their gut microbiota. The translocation ability of the Ec1 strain was validated in a mouse pneumonia model, where it caused more severe lung damage. Furthermore, elevated levels of Escherichia-Shigella were detected in the lung tissues of colitis mice, suggesting that gut-to-lung bacterial translocation may occur in a severely inflamed host, potentially leading to pneumonia.
Conclusions: This study demonstrates the gut-to-lung translocation of E. coli and B. cenocepacia, highlighting their role in the development and progression of VAP in ICU patients. These findings provide valuable insights for implementing targeted prevention and treatment strategies for VAP in ICU settings.