Mahmud Hafij Al, Garcia Randy, Garcia Alexsis, Baishya Jiwasmika, Wakeman Catherine A
Department of Biological Sciences, Texas Tech University, Lubbock, Texas, USA.
The Assam Royal Global University, Guwahati, Assam, India.
Microbiol Spectr. 2024 Jul 11;12(8):e0422623. doi: 10.1128/spectrum.04226-23.
Chronic infections harbor multiple pathogens where dynamic interactions between members of the polymicrobial community play a major role in determining the infection outcome. For example, in a nutrient-rich polymicrobial infection, bacteria have the potential to undergo evolutionary changes that impair their ability to synthesize essential metabolites. This adaptation may facilitate metabolic interdependencies between neighboring pathogens and lead to difficult-to-treat chronic infections. Our research group previously demonstrated that (PA) and (SA), typically considered classical competitors, can adopt a cooperative lifestyle through bi-directional purine exchange medicated by exogenous DNA (eDNA) release. To further validate our initial findings, in this study, we investigated the potential exchange of pyrimidine between PA and other pathogens, which is another constituent of DNA. In our findings, we observed that a pyrimidine-deficient transposon mutant strain of PA showed improved growth when co-cultured with wild-type PA, SA, (AB), and (EF). Additionally, improved fitness of pyrimidine-deficient PA was further observed in chemical complementation with eDNA and uridine-5'-monophosphate. Interestingly, the rescue of PA growth through eDNA complementation is not as effective as in intact cells, such as SA, AB, EF, and wild-type PA, implying that eDNA is a lesser contributor to this metabolic complementation. Also, the exchange mechanism between pathogens involves more active mechanisms beyond simple eDNA or metabolite release. Our data further highlights the importance of cell-to-cell contact for effective and increased metabolic complementation.
This research holds crucial implications for combating chronic infections, where multiple pathogens coexist and interact within the same environment. By uncovering the dynamic exchange of pyrimidines between (PA) and (SA), our study reveals a previously unrecognized aspect of interspecies cooperation. The observed enhanced growth of a pyrimidine-deficient PA strain when co-cultured with SA suggests potential avenues for understanding and disrupting bacterial metabolic interdependencies in chronic infection settings. Furthermore, our findings highlight the mechanisms involved in metabolic exchange, emphasizing the importance of cell-to-cell contact. This research explored essential metabolic interactions to address the challenges posed by difficult-to-treat chronic infections.
慢性感染中存在多种病原体，微生物群落成员之间的动态相互作用在决定感染结果方面起着主要作用。例如，在营养丰富的多微生物感染中，细菌有可能发生进化变化，损害其合成必需代谢物的能力。这种适应性可能促进相邻病原体之间的代谢相互依赖，并导致难以治疗的慢性感染。我们的研究小组之前证明，通常被认为是经典竞争者的铜绿假单胞菌（PA）和金黄色葡萄球菌（SA），可以通过由外源DNA（eDNA）释放介导的双向嘌呤交换，采取合作的生存方式。为了进一步验证我们的初步发现，在本研究中，我们研究了PA与其他病原体之间嘧啶的潜在交换，嘧啶是DNA的另一种成分。在我们的研究结果中，我们观察到，与野生型PA、SA、鲍曼不动杆菌（AB）和屎肠球菌（EF）共培养时，PA的嘧啶缺陷转座子突变株生长得到改善。此外，在与eDNA和尿苷-5'-单磷酸的化学互补中，进一步观察到嘧啶缺陷型PA的适应性提高。有趣的是，通过eDNA互补拯救PA生长的效果不如在完整细胞（如SA、AB、EF和野生型PA）中有效，这意味着eDNA对这种代谢互补的贡献较小。此外，病原体之间的交换机制涉及比简单的eDNA或代谢物释放更活跃的机制。我们的数据进一步强调了细胞间接触对于有效和增强代谢互补的重要性。
这项研究对于对抗慢性感染具有至关重要的意义，在慢性感染中，多种病原体在同一环境中共存并相互作用。通过揭示铜绿假单胞菌（PA）和金黄色葡萄球菌（SA）之间嘧啶的动态交换，我们的研究揭示了种间合作一个以前未被认识的方面。与SA共培养时，观察到嘧啶缺陷型PA菌株生长增强，这为理解和破坏慢性感染环境中细菌的代谢相互依赖提供了潜在途径。此外，我们的研究结果突出了代谢交换所涉及的机制，强调了细胞间接触的重要性。这项研究探索了基本的代谢相互作用，以应对难以治疗的慢性感染带来的挑战。
