Data_Sheet_1_The Good and the Bad: Ecological Interaction Measurements Between the Urinary Microbiota and Uropathogens.docx

The human body harbors numerous populations of microorganisms in various ecological niches. Some of these microbial niches, such as the human gut and the respiratory system, are well studied. One system that has been understudied is the urinary tract, primarily because it has been considered sterile in the absence of infection. Thanks to modern sequencing and enhanced culture techniques, it is now known that a urinary microbiota exists. The implication is that these species live as communities in the urinary tract, forming microbial ecosystems. However, the interactions between species in such an ecosystem remains unknown. Various studies in different parts of the human body have highlighted the ability of the pre-existing microbiota to alter the course of infection by impacting the pathogenicity of bacteria either directly or indirectly. For the urinary tract, the effect of the resident microbiota on uropathogens and the phenotypic microbial interactions is largely unknown. No studies have yet measured the response of uropathogens to the resident urinary bacteria. In this study, we investigate the interactions between uropathogens, isolated from elderly individuals suffering from UTIs, and bacteria isolated from the urinary tract of asymptomatic individuals using growth measurements in conditioned media. We observed that bacteria isolated from individuals with UTI-like symptoms and bacteria isolated from asymptomatic individuals can affect each other’s growth; for example, bacteria isolated from symptomatic individuals affect the growth of bacteria isolated from asymptomatic individuals more negatively than vice versa. Additionally, we show that Gram-positive bacteria alter the growth characteristics differently compared to Gram-negative bacteria. Our results are an early step in elucidating the role of microbial interactions in urinary microbial ecosystems that harbor both uropathogens and pre-existing microbiota.

人体各类生态位中定植有大量微生物种群。其中部分微生物生态位，如人体肠道与呼吸系统，已得到充分研究。尿路系统是研究相对不足的系统之一，这主要是因为此前学界认为，未发生感染时尿路处于无菌状态。得益于现代测序技术与改良培养技术，如今已证实尿路中存在微生物群（microbiota）。这意味着这些微生物以群落形式定植于尿路，构成微生物生态系统。然而，该生态系统内物种间的相互作用仍不明晰。人体不同部位的多项研究均表明，预先定植的微生物群（pre-existing microbiota）可通过直接或间接影响细菌致病性，从而改变感染进程。但就尿路系统而言，定植微生物群对尿路致病菌（uropathogens）的影响，以及微生物间的表型相互作用，在很大程度上仍未明确。目前尚无研究检测尿路致病菌对尿路定植细菌的应答反应。本研究借助条件培养基（conditioned media）中的生长检测手段，探究两类细菌的相互作用：一类是从罹患尿路感染（Urinary Tract Infection, UTI）的老年个体体内分离得到的尿路致病菌，另一类是从无症状个体尿路中分离得到的细菌。研究结果显示，从伴有尿路感染样症状个体体内分离的细菌，与无症状个体分离的细菌可相互影响对方的生长；例如，前者对后者生长的抑制作用要强于后者对前者的抑制作用。此外，本研究还发现，革兰氏阳性菌（Gram-positive bacteria）与革兰氏阴性菌（Gram-negative bacteria）对生长特性的调控模式存在差异。本研究结果为阐明同时存在尿路致病菌与预先定植微生物群的尿路微生物生态系统中，微生物相互作用的功能机制迈出了初步探索性的一步。