Gene Loss and Acquisition in Lineages of Pseudomonas aeruginosa Evolving in Cystic Fibrosis Patient Airways

Abstract

Genome analyses have documented that there are differences in gene repertoire between evolutionary distant lineages of the same bacterial species; however, less is known about microevolutionary dynamics of gene loss and acquisition within bacterial lineages as they evolve over years. Here, we analyzed the genomes of 45 Pseudomonas aeruginosa lineages evolving in the lungs of cystic fibrosis (CF) patients to identify genes that are lost or acquired during the first years of infection. On average, lineage genome content changed by 88 genes (range, 0 to 473). Genes were more often lost than acquired, and prophage genes were more variable than bacterial genes. We identified convergent loss or acquisition of the same genes across lineages, suggesting selection for loss and acquisition of certain genes in the host environment. We found that a notable proportion of such genes are associated with virulence; a trait previously shown to be important for adaptation. Furthermore, we also compared the genomes across lineages to show that the within-lineage variable genes (i.e., genes that had been lost or acquired during the infection) often belonged to genomic content not shared across all lineages. In sum, our analysis adds to the knowledge on the pace and drivers of gene loss and acquisition in bacteria evolving over years in a human host environment and provides a basis to further understand how gene loss and acquisition play roles in lineage differentiation and host adaptation. IMPORTANCE Bacterial airway infections, predominantly caused by P. aeruginosa, are a major cause of mortality and morbidity of CF patients. While short insertions and deletions as well as point mutations occurring during infection are well studied, there is a lack of understanding of how gene loss and acquisition play roles in bacterial adaptation to the human airways. Here, we investigated P. aeruginosa within-host evolution with regard to gene loss and acquisition. We show that during long-term infection P. aeruginosa genomes tend to lose genes, in particular, genes related to virulence. This adaptive strategy allows reduction of the genome size and evasion of the host’s immune response. This knowledge is crucial to understand the basic mutational steps that, on the timescale of years, diversify lineages and adds to the identification of bacterial genetic determinants that have implications for CF disease.

An Organ System-Based Synopsis ofPseudomonas aeruginosaVirulence

“…The evolutionary process of natural selection, gene loss and acquisition [ 217 , 218 ], natural genetic transformation [ 219 ], horizontal gene transfer [ 220 ], and emergence of hypermutators during acute VAP and/or chronic CF lung infection can lead to changes in antimicrobial resistance (AMR) and virulence behavior of P. aeruginosa [ 210 , 221 ]. The P. aeruginosa pan-genome contains a collection of 3,010 putative and plasmids DNA genes obtained by horizontal gene transfer with 5% to 12% encoding AMR and virulence genes [ 222 ].…”

A genomic perspective across Earth’s microbiomes reveals that genome size in Archaea and Bacteria is linked to ecosystem type and trophic strategy

“…For a complete list of archaeal phyla please see Figure 3. Fusobacteriota (94) Deinococcota (93) Thermotogota (83) Fibrobacterota (82) Eremiobacterota (75) Synergistota (64) Dependentiae (58) Binatota (57) Chloroflexota_A (52…”

“…In the same study, highly dynamic genomes were found presenting these evolutionary events 25 times more often than the most stable genomes. This tendency that gene loss is more prevalent than gene gain has also been described in short term in host-associated Pseudomonas aeruginosa (Gammaproteobacteria) (58). There, clinical isolates of P. aeruginosa indicate gene loss rates six times greater than gene acquisition during the first year of a chronical infection as an adaptive strategy to avoid the host's immune response.…”

Analysis of the Phospholipid Profile of the Collection Strain PAO1 and Clinical Isolates of Pseudomonas aeruginosa in Relation to Their Attachment Capacity

“…Here we tested an alternative strategy to identify potential molecular actors involved in the attachment phase, in the aim to fight against biofilms. This strategy is based on the comparison of two pools of clinical strains sharing a common phenotype regarding their AC within a pool but presumed genetically different between and within the pools [ 44 , 45 ]. Thus, in an ideal situation, a PL having a constant relative quantity within strains of the same pool (LAC or HAC) but systematically differentiating the strains of different pools (LAC vs. HAC) might be a molecular actor linked to the attachment phenotype and therefore, a potential molecular target.…”