Mechanism Of Persistent Colonization Of Multidrug Resistant Pseudomonas Aeruginosa In COPD Airways

Persistent infections caused by multidrug-resistant bacteria pose a significant threat to worldwide public health and safety.Studying the colonization process of bacteria and the evolutionary selection pressure in human hosts will contribute to understanding the underlying molecular mechanism of pathogenesis and tracing bacterial transmission networks.The frequent antibiotic treatment of patients with chronic obstructive pulmonary disease(COPD)typically leads to the enrichment of multidrug-resistant Pseudomonas aeruginosa(PA).However,the evolutionary trajectory and potential vital mutations that may contribute to the persistent colonization of P.aeruginosa in COPD airways remain unclear.To address this issue,this research recruited 15 COPD patients from the Affiliated Hospital of Chengdu University,collected respiratory tract samples every two weeks,and isolated P.aeruginosa.Over the duration of the study,209 strains were isolated.The study conducted a horizontal survey of the phenotypes,drug resistance,and integrity of the quorum sensing system(QS)of clinical P.aeruginosa to assess the overall adaptability of the isolated strains.The findings revealed a positive or negative connection between antibiotic resistance and phenotypes,implying that the two may have a synergistic development trend.To comprehend the constant change process of adaptive colonization,P.aeruginosa from four patients(L,W,C,M)were sampled several times.This study compared pyocyanin,biofilm,extracellular protease,and motility to characterize the progression of virulence from quantitative to qualitative during colonization.Long-term COPD strains have down-regulated or deleted pathogenicity,including extracellular protease.The study sequenced the genomes of representative strains screened after phenotypic identification,constructed the phylogenetic tree using single nucleotide polymorphism and multiple site sequence typing,and depicted the multithreaded parallel evolution route of clinical subgroup evolution.Hospital-based P.aeruginosa transmission was observed.Using transcriptome sequencing,the study identified the functional categories of KEGG pathway and GO that were enriched by the differently expressed genes of the evolutionary strains compared to the original isolates,solving the dilemma of phenotype and genotype evolution being unrelated.The work showed that the QS system function is frequently down-regulated or eliminated during ongoing colonization.Functional and nonfunctional QS subpopulations co-colonize COPD patients’ lungs.The study used Caenorhabditis elegans and mice to simulate the population quantity and proportion of clinical QS complete and deficient strains when colonized separately and together,to compare their persistent colonization and host consequences.This study implies that QS-deficient strains may colonize successfully.Overall,this study conducted a horizontal survey and long-term monitoring of clinical P.aeruginosa.The work addressed the virulence and transcriptional landscape in COPD using phenotypes,genome sequencing,transcriptome sequencing,and animal models.The study examined how subgroup structural changes affect the host,explained the association between Acute exacerbation of COPD(AECOPD)and P.aeruginosa,and improved our knowledge of the biological process and molecular mechanism of recurring COPD respiratory infection.