Department of Theoretical Biology, Max Planck Institute for Evolutionary Biology, 24306 Plön, Germany.
Dioscuri Centre for Physics and Chemistry of Bacteria, Institute of Physical Chemistry (IChF), Polish Academy of Sciences, 01-224 Warsaw, Poland.
ISME J. 2024 Jan 8;18(1). doi: 10.1093/ismejo/wrae191.
Treatment of urinary tract infections and the prevention of their recurrence is a pressing global health problem. In a urinary infection, pathogenic bacteria not only reside in the bladder lumen but also attach to and invade the bladder tissue. Planktonic, attached, and intracellular bacteria face different selection pressures from physiological processes such as micturition, immune response, and antibiotic treatment. Here, we use a mathematical model of the initial phase of infection to unravel the effects of these different selective pressures on the ecological and evolutionary dynamics of urinary infections. We explicitly model planktonic bacteria in the bladder lumen, bacteria attached to the bladder wall, and bacteria that have invaded the epithelial cells of the bladder. We find that the presence of non-planktonic bacteria substantially increases the risk of infection establishment and affects evolutionary trajectories leading to resistance during antibiotic treatment. We also show that competitive inoculation with a fast-growing non-pathogenic strain can reduce the pathogen load and increase the efficacy of an antibiotic, but only if the antibiotic is used in moderation. Our study shows that including different compartments is essential to create more realistic models of urinary infections, which may help guide new treatment strategies.
治疗尿路感染和预防其复发是一个紧迫的全球健康问题。在尿路感染中，致病菌不仅存在于膀胱腔中，还附着并侵袭膀胱组织。浮游、附着和细胞内细菌面临着来自排尿、免疫反应和抗生素治疗等生理过程的不同选择压力。在这里，我们使用感染初始阶段的数学模型来揭示这些不同的选择压力对尿路感染的生态和进化动态的影响。我们明确地对膀胱腔中的浮游细菌、附着在膀胱壁上的细菌和已经侵入膀胱上皮细胞的细菌进行建模。我们发现，非浮游细菌的存在大大增加了感染建立的风险，并影响了在抗生素治疗期间导致耐药性的进化轨迹。我们还表明，用快速生长的非致病性菌株进行竞争性接种可以减少病原体负荷并提高抗生素的疗效，但前提是抗生素使用适度。我们的研究表明，包括不同的隔室对于创建更现实的尿路感染模型至关重要，这可能有助于指导新的治疗策略。
