Evolution of biofilm-adapted gene expression profiles in lasR-deficient clinical Pseudomonas aeruginosa isolates

Abstract

The overall success of a pathogenic microbe depends on its ability to efficiently adapt to challenging conditions in the human host. Long-term evolution experiments track and predict adaptive trajectories and have contributed significantly to our understanding of the driving forces of bacterial adaptation. In this study, we conducted a cross-sectional study instead of long-term longitudinal evolution experiments. We analyzed the transcriptional profiles as well as genomic sequence variations of a large number of clinical Pseudomonas aeruginosa isolates that have been recovered from different infected human sites. Convergent changes in gene expression patterns were found in different groups of clinical isolates. The majority of repeatedly observed expression patterns could be attributed to a defective lasR gene, which encodes the major quorum-sensing regulator LasR. Strikingly, the gene expression pattern of the lasR-defective strains appeared to reflect a transcriptional response that evolves in a direction consistent with growth within a biofilm. In a process of genetic assimilation, lasR-deficient P. aeruginosa isolates appear to constitutively express a biofilm-adapted transcriptional profile and no longer require a respective environmental trigger. Our results demonstrate that profiling the functional consequences of pathoadaptive mutations in clinical isolates reveals long-term evolutionary pathways and may explain the success of lasR mutants in the opportunistic pathogen P. aeruginosa in a clinical context.

Molecular study of quorum sensing and biofilm formation genes in Pseudomonas aeruginosa isolated from UTIs patients

“…The results in the present study were evaluated statistically via T test and Chi square using Statistical Package for Social Sciences (SPSS) program version 23 at a probability of (P≤ 0.05) as a significant level between the parameters of the present study such as gender, age, and source of samples. P value of <0.05 was considered significant (21).…”

Resistance Is Not Futile: The Role of Quorum Sensing Plasticity in Pseudomonas aeruginosa Infections and Its Link to Intrinsic Mechanisms of Antibiotic Resistance

“…Curiously, while levels of the examined secreted virulence factors decreased concomitantly with 3OC 12 HSL and PQS levels, C 4 HSL levels remained steady across isolates, indicating a rhl independence that might be critical to the maintenance of chronic infections [131]. Indeed, a longitudinal study of several clinical isolates from different sources of infected hosts revealed that LasR-independent transcription and biofilm growth and maintenance were reliant on RhlR-dependent transcriptional activity [132]. Interestingly, rhlR regulation in lasR mutant strains was shown to proceed via PhoB in phosphate limiting conditions in laboratory strains, but this requirement was not observed in clinical isolates, indicating that there are multiple factors responsible for the maintenance of RhlR-dependent signaling in these isolates (Figure 1d) [81].…”

Molecular study of quorum sensing and biofilm formation genes in pseudomonas aeruginosa isolated from UTIs patients

“…Positive results were detected by the presence of (155 bp) bands when compared with ladder as shown Figure . (1,2,5,6,9,10,12,13,14,15,16,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32) Amplifying of LasR gene, Lanes (3,4,7,8,11,17) No amplifying of LasR gene…”