Metabolic pathways of Pseudomonas aeruginosa involved in competition with respiratory bacterial pathogens

Abstract

Background: Chronic airway infection by Pseudomonas aeruginosa considerably contributes to lung tissue destruction and impairment of pulmonary function in cystic-fibrosis (CF) patients. Complex interplays between P. aeruginosa and other co-colonizing pathogens including Staphylococcus aureus, Burkholderia sp., and Klebsiella pneumoniae may be crucial for pathogenesis and disease progression.Methods: We generated a library of PA14 transposon insertion mutants to identify P. aeruginosa genes required for exploitative and direct competitions with S. aureus, Burkholderia cenocepacia, and K. pneumoniae.Results: Whereas wild-type PA14 inhibited S. aureus growth, two transposon insertions located in pqsC and carB, resulted in reduced growth inhibition. PqsC is involved in the synthesis of 4-hydroxy-2-alkylquinolines (HAQs), a family of molecules having antibacterial properties, while carB is a key gene in pyrimidine biosynthesis. The carB mutant was also unable to grow in the presence of B. cepacia and K. pneumoniae but not Escherichia coli and S. epidermidis. We further identified a transposon insertion in purF, encoding a key enzyme of purine metabolism. This mutant displayed a severe growth deficiency in the presence of Gram-negative but not of Gram-positive bacteria. We identified a beneficial interaction in a bioA transposon mutant, unable to grow on rich medium. This growth defect could be restored either by addition of biotin or by co-culturing the mutant in the presence of K. pneumoniae or E. coli.Conclusion: Complex interactions take place between the various bacterial species colonizing CF-lungs. This work identified both detrimental and beneficial interactions occurring between P. aeruginosa and three other respiratory pathogens involving several major metabolic pathways. Manipulating these pathways could be used to interfere with bacterial interactions and influence the colonization by respiratory pathogens.

Cystic Fibrosis Patients Infected With Epidemic Pseudomonas aeruginosa Strains Have Unique Microbial Communities

“…Indeed, we suspect that this may be a primary means of ePA pathogenesis. These may occur through the production of a number of secondary metabolites that act to shape the surrounding community structure (Tashiro et al, 2013;Beaume et al, 2015;Stubbendieck and Straight, 2016). This aligns with our main observation that PES is more likely to dominate CF respiratory communities than uPA strains, suggesting that PES may have an enhanced competitive advantage in airway communities.…”

Pseudomonas aeruginosa DesB Promotes Staphylococcus aureus Growth Inhibition in Coculture by Controlling the Synthesis of HAQs

“…aureus growth inhibition-associated materials, such as 4-hydroxy-2-alkylquinolines (HAQs), which have antimicrobial activity. These HAQs include 4-hydroxy-2-heptylquinoline (HHQ), 4-hydroxy-2-nonylquinoline (HNQ), pseudomonas quinolone signal (PQS), and 4-hydroxy-2-heptylquinoline N -oxide (HQNO) [ 35 ]. Synthesis of these HAQs is mainly controlled by the P .…”

Microbial Interactions in the Cystic Fibrosis Airway

“…The chronicity of specific infections (27), their interactions with human host defenses, and their clinical outcomes have been studied previously (28). Microbial species-to-species interactions among pathogens similar to those found in the CF airway have been studied in various in vitro and nonhuman in vivo model systems (17,18,(29)(30)(31)(32)(33)(34)(35)(36)(37), and the clinical effects of the combination of P. aeruginosa and MSSA have been explored (38), but interspecies microbial interactions in the CF airway have been minimally explored, and recent calls to expand this knowledge base remain outstanding (16,39).…”

“…While antibiotic therapy may play a role, existing infections themselves appear to alter the rest of the microbiota (7,(16)(17)(18)(19) and may thus alter the clinical disease course. In vitro and nonhuman in vivo models show evidence of interspecies interaction between P. aeruginosa and other pathogens, including MSSA and Burkholderia cenocepacia.…”