Comparative Genomic Analysis of Non-typeable Haemophilus Influenzae in Children with Acute and Chronic Pneumonia versus Healthy Controls

Abstract

AbstractNon-typeable Hemophilus Influenzae (NTHi) is a common pathogen that can cause a range of respiratory infections, including children pneumonia. However, NTHi can also be found in the upper respiratory tracts of healthy individuals and may not cause any symptoms. The transition of NTHi from a commensal to a pathogenic state is still not well understood. In this study, we aimed to investigate the genomic differences between NTHi isolated from healthy children and those with acute or chronic community-acquired pneumonia (CAP) to better understand the mechanisms underlying this transition. Genomic differences between NTHi isolated from the nasopharynx swabs of healthy children and the bronchoalveolar lavage fluids of children with acute or chronic community-acquired pneumonia (CAP) were analyzed and compared. The study used bGWAS (Bacterial Genome-Wide Association Study) analysis to identify phenotype convergence genes among the three groups and conducted gene enrichment, antibiotic resistance, and virulence factor analyses. Findings showed heterogeneity in the NTHi genomes among the three groups, and various phenotype transition genes that represent the evolution from a healthy to an acute or chronic clinical phenotype were identified. Multiple pathways were found to be involved in the pathogenicity and chronic adaptation of NTHi, including metabolism, synthetic, mismatch repair, glycolysis, and gluconeogenesis. Furthermore, the analysis indicated that antibiotic resistance genes against cephalosporin were commonly present in NTHi isolated from acute and chronic pneumonia patients. Overall, this genomic analysis of NTHi offers promising contributions toward precise clinical diagnosis and treatment.ImportanceUnderstanding the transition of Non-typeable Hemophilus Influenzae (NTHi) from a harmless commensal organism to a dangerous pathogen responsible for respiratory infections such as pneumonia in children is crucial for developing more effective diagnostic and treatment strategies. The importance of this study lies in its comprehensive examination of the genomic differences between NTHi strains found in healthy individuals and those causing acute or chronic community-acquired pneumonia (CAP). By employing advanced techniques like bGWAS (Bacterial Genome-Wide Association Study), the research sheds light on the complex genetic underpinnings that facilitate NTHi’s shift towards pathogenicity. Identifying specific genes associated with phenotype transitions, antibiotic resistance, and virulence factors not only deepens our understanding of NTHi’s biology but also paves the way for targeted therapies that could mitigate the impact of this pathogen on public health. Furthermore, the discovery of multiple pathways involved in NTHi’s adaptation to chronic infection states highlights the multifaceted nature of bacterial pathogenesis and underscores the necessity of a nuanced approach to combating these infections. This study’s findings are particularly significant given the growing concern over antibiotic resistance, as evidenced by the prevalence of cephalosporin-resistant genes in strains isolated from pneumonia patients. Thus, this research contributes importantly to the ongoing efforts to refine our approach to diagnosing and treating respiratory infections caused by NTHi, with potential implications for reducing the burden of these diseases on affected populations worldwide.