AUTHOR=Beaume Marie , Köhler Thilo , Fontana Thierry , Tognon Mikael , Renzoni Adriana , van Delden Christian 

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

JOURNAL=Frontiers in Microbiology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.00321

DOI=10.3389/fmicb.2015.00321

ISSN=1664-302X

ABSTRACT=<p><bold>Background:</bold> Chronic airway infection by <italic>Pseudomonas aeruginosa</italic> considerably contributes to lung tissue destruction and impairment of pulmonary function in cystic-fibrosis (CF) patients. Complex interplays between <italic>P. aeruginosa</italic> and other co-colonizing pathogens including <italic>Staphylococcus aureus</italic>, <italic>Burkholderia</italic> sp., and <italic>Klebsiella pneumoniae</italic> may be crucial for pathogenesis and disease progression.</p><p><bold>Methods:</bold> We generated a library of PA14 transposon insertion mutants to identify <italic>P. aeruginosa</italic> genes required for exploitative and direct competitions with <italic>S. aureus</italic>,<italic> Burkholderia cenocepacia,</italic> and<italic> K. pneumoniae</italic>.</p><p><bold>Results:</bold> Whereas wild-type PA14 inhibited <italic>S. aureus</italic> growth, two transposon insertions located in <italic>pqsC and carB</italic>, 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 <italic>carB</italic> is a key gene in pyrimidine biosynthesis. The <italic>carB</italic> mutant was also unable to grow in the presence of <italic>B. cepacia</italic> and <italic>K. pneumoniae</italic> but not<italic> Escherichia coli</italic> and <italic>S. epidermidis</italic>. We further identified a transposon insertion in <italic>purF</italic>, 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 <italic>bioA</italic> 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 <italic>K. pneumoniae</italic> or <italic>E. coli</italic>.</p><p><bold>Conclusion:</bold> Complex interactions take place between the various bacterial species colonizing CF-lungs. This work identified both detrimental and beneficial interactions occurring between <italic>P. aeruginosa</italic> 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.</p>