Pseudomonas aeruginosa Relies on a Phosphoketolase to Support Anaerobic Survival Under Reductive Stress

Across diverse contexts, bacteria experience loss of electron acceptors due to fluctuating environmental conditions, leading to growth-arrest and reductive stress. Yet, microbial metabolism has been primarily studied with cells growing under nutrient-replete conditions. To study how cells preserve metabolic flux under reductively stressed growth-arrest, we explored how the opportunistic pathogen Pseudomonas aeruginosa remodels its metabolism under such conditions. During anaerobic survival on glucose, P. aeruginosa utilizes the upper Embden-Meyerhoff-Parnas pathway and pentose-phosphate pathway to generate metabolite precursors for a previously undescribed phosphoketolase (herein termed xfp) used to produce acetyl-P and indirectly ATP via subsequent acetate formation. This re-routing bypasses P. aeruginosa's canonical glucose-catabolizing Entner-Doudoroff pathway (EDP), allowing for metabolic flux without exacerbating reductive stress. Moreover, anaerobic survival on diverse carbon sources triggers purine degradation and metabolite accumulation, requiring xfp to maintain metabolic balance and viability. Thus, our data suggest that phosphoketolases may play an additional role in ribonucleotide balance. This study expands our understanding of P. aeruginosa's anaerobic survival strategies and serves as a reminder that large gaps remain in our understanding of growth arrest physiology even in well-studied model organisms, highlighting the potential for basic discovery in the realm of non-growth metabolism.