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. 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.

金黄色葡萄球菌（Staphylococcus aureus, Sa）与鲍曼不动杆菌（Acinetobacter baumannii, Ab）常从重症且难治的多微生物感染病灶中共同分离得到。本研究结合湿实验室实验与计算机模拟建模，采用代表性实验室菌株及临床共分离菌株，解析Ab与Sa之间复杂的相互作用机制。该系统性研究方法揭示了Sa可通过表达酚溶性调控蛋白（phenol-soluble modulins）对Ab产生部分干扰效应。此外，本研究还观察到交叉营养机制：Sa可通过提供乙偶姻（acetoin）作为替代碳源，促进Ab的生长。本研究首次剖析了Ab与Sa之间兼具竞争与协同的动态相互作用网络，属于该领域的开创性工作。通过本研究结果，我们阐明了二者在多微生物感染环境中共存的生态学机制。本研究不仅深化了学界对该类感染的认知，更为这类难治性感染的潜在治疗策略开辟了新路径。本研究的目标为探究鲍曼不动杆菌A118暴露于金黄色葡萄球菌USA300后的效应，反之亦然。实验中将鲍曼不动杆菌A118培养于金黄色葡萄球菌USA300的无细胞条件培养基（Cell-Free Conditioned Medium, CFCM）中，并以仅培养于胰蛋白胨大豆肉汤（Tryptic Soy Broth, TSB）培养基的鲍曼不动杆菌A118作为对照。此外，将金黄色葡萄球菌USA300培养于鲍曼不动杆菌A118的无细胞条件培养基中，并以仅培养于TSB培养基的金黄色葡萄球菌USA300作为对照。所有对比分析均基于Illumina双端RNA测序（RNA-Seq）数据完成。