Investigating the Pulmonary Host Response of Acinetobacter baumannii Infection-Associated Pneumonia by Metagenomic Next-Generation Sequencing

<b>Background:</b> For investigating the host response in <i>Acinetobacter baumannii</i> associated pneumonia, we analyzed the host genetic sequences obtained from metagenomic next-generation sequencing (mNGS). <b>Methods:</b> The samples for mNGS were bronchoalveolar lavage fluid (BALF) collected from the lungs of patients infected with <i>A. baumannii</i> and from patients without bacterial infections. BALF samples from patients with pneumonia were collected from the lungs of patients infected with <i>A. baumannii</i> with New Delhi metallo-β-lactamase (NDM, before treatment), A. baumannii with NDM (post-treatment), <i>A. baumannii</i> without resistant genes, and those without bacterial infection. Partek was used for investigating enriched functions and pathways related to the pulmonary host response to pneumonia caused by <i>A. baumannii</i> with NDM infection and <i>A. baumannii</i> without antimicrobial-resistant genes. The STRING was employed for identifying protein interaction pathways related to the pulmonary host response to pneumonia caused by <i>A. baumannii</i> without antimicrobial-resistant genes. <b>Results:</b> In pulmonary host response to pneumonia caused by <i>A. baumannii</i> with NDM, five immune system-related pathways and five pathways related to signal transduction were identified. No significant differences were observed in the immune system and signal transduction pathways in the pulmonary host response to pneumonia caused by <i>A. baumannii</i> without antimicrobial-resistant genes. However, significant differences were noted in the phagosome, ferroptosis, and regulation of the actin cytoskeleton in cellular processes. <b>Conclusions:</b> mNGS provides information not only on pathogen gene expression but also on host gene expression. In this study, we found that pneumonia with <i>A. baumannii</i> carrying the NDM resistance gene triggers stronger immune responses in the lung, while pneumonia with <i>A. baumannii</i> lacking antimicrobial resistance genes is more linked to iron-related pathways.