Essential O2-responsive genes of Pseudomonas aeruginosa and their network revealed by integrating dynamic data from inverted conditions

Abstract

Identification of the gene network through which Pseudomonas aeruginosa PAO1 (PA) adapts to altered oxygen-availability environments is essential for a better understanding of stress responses and pathogenicity of PA. We performed high-time-resolution (HTR) transcriptome analyses of PA in a continuous cultivation system during the transition from high oxygen tension to low oxygen tension (HLOT) and the reversed transition from low to high oxygen tension (LHOT). From those genes responsive to both transient conditions, we identified 85 essential oxygen-availability responsive genes (EORGs), including the expected ones (arcDABC) encoding enzymes for arginine fermentation. We then constructed the regulatory network for the EORGs of PA by integrating information from binding motif searching, literature and HTR data. Notably, our results show that only the sub-networks controlled by the well-known oxygen-responsive transcription factors show a very high consistency between the inferred network and literature knowledge, e.g. 87.5% and 83.3% of the obtained sub-network controlled by the anaerobic regulator (ANR) and a quorum sensing regulator RhIR, respectively. These results not only reveal stringent EORGs of PA and their transcription regulatory network, but also highlight that achieving a high accuracy of the inferred regulatory network might be feasible only for the apparently affected regulators under the given conditions but not for all the expressed regulators on a genome scale.

The OpdQ porin of Pseudomonas aeruginosa is regulated by environmental signals associated with cystic fibrosis including nitrate‐induced regulation involving the NarXL two‐component system

“…Oxygen availability has become the subject of intense research for trying to understand the adaptation and persistence processes of chronic P. aeruginosa infections in CF patients (Worlitzsch et al 2002;Hassett et al 2009). Transcriptome analyzes of P. aeruginosa have demonstrated that oxygen content affects the expression of numerous genes associated with metabolic processes, quorum sensing, biofilm formation, alginate biosynthesis, and antibiotic tolerance (Hassett 1996;Borriello et al 2004;Alvarez-Ortega and Harwood 2007;He et al 2014). Our findings demonstrate that OpdQ is negatively regulated at the transcriptional level under hypoxic growth conditions (Fig.…”

“…; Schobert and Jahn ; He et al. ). To determine whether the opdQ promoter contains a NarL binding motif, an in silico analysis was performed.…”

“…; Alvarez‐Ortega and Harwood ; He et al. ). Our findings demonstrate that OpdQ is negatively regulated at the transcriptional level under hypoxic growth conditions (Fig.…”

“…Pseudomonas aeruginosa responds to nitrate in low oxygen via the NarXL two-component system which functions by regulating genes involved in nitrate and nitrite respiration to control growth under hypoxic and anaerobic conditions (Alvarez-Ortega and Harwood 2007;Schreiber et al 2007;Schobert and Jahn 2010;He et al 2014). To determine whether the opdQ promoter contains a NarL binding motif, an in silico analysis was performed.…”

ADAGE analysis of publicly available gene expression data collections illuminatesPseudomonas aeruginosa-hostinteractions

“…Node 42 showed low activity (blue) in the anr mutant, even in low oxygen conditions that would otherwise be expected to activate Anr (grey). In addition, we also evaluated the activity of Node 42 in datasets where the responses to different oxygen concentrations were compared and found that again, the activity of Node 42 was modulated by oxygen availability (E-GEOD-33160 (39) and E-GEOD-52445 (40) in Figure 4A). E-GEOD-52445 is a high-time-resolution analysis of P. aeruginosa transiting from high oxygen tension to low oxygen tension and then reverse (40).…”