Competitive Inhibition and Mutualistic Growth in Polymicrobial Infections: Deciphering Staphylococcus aureus – Acinetobacter baumannii Interaction Dynamics
Staphylococcus aureus (Sa) and Acinetobacter baumannii (Ab) are frequently co-isolated from polymicrobial infections that are severe and recalcitrant to therapy. Here, we apply a combination of wet-lab experiments and in silico modeling to unveil the intricate nature of the Ab/Sa interaction using both, representative laboratory strains and strains co-isolated from clinical samples. This comprehensive methodology allowed uncovering Sa's capability to exert a partial interference on Ab by the expression of phenol-soluble modulins. Additionally, we observed a cross-feeding mechanism, wherein Sa supports Ab's growth by providing acetoin as an alternative carbon source. This study marks the pioneering work to dissect Ab/Sa interaction dynamics wherein competitive and cooperative dynamics can intertwine. Through our findings, we illuminate the ecological mechanisms underpinning their coexistence in the context of polymicrobial infections. Our research not only enriches our understanding but also opens doors to potential therapeutic avenues in managing these challenging infections. Overall design: Aim of the study is to understand the effect of exposure of Acinetobacter baumannii A118 to  Staphylococcus aureus USA300 and vice versa. Acinetobacter baumannii A118 was cultivated in Cell-Free Conditioned Medium (CFCM) of Staphylococcus aureus USA300, with Acinetobacter baumannii A118 cultivated in TSB medium as control. Furthermore Staphylococcus aureus USA300 was cultivated in CFCM of Acinetobacter baumannii A118, with Staphylococcus aureus USA300 in TSB medium as control. All comparisons were done with Illumina Paired-End RNA-Seq data.