Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
mBio. 2024 Oct 16;15(10):e0331923. doi: 10.1128/mbio.03319-23. Epub 2024 Sep 17.
is a globally disseminated pathogen that is the cause of over 100 million infections per year. The resulting diseases are dependent upon host susceptibility and the infecting serovar. As serovar Typhimurium induces a typhoid-like disease in mice, this model has been used extensively to illuminate various aspects of infection and host responses. Due to the severity of infection in this model, researchers often use strains of mice resistant to infection or attenuated . Despite decades of research, many aspects of infection and fundamental biology remain poorly understood. Here, we use a transposon insertion sequencing technique to interrogate the essential genomes of widely used isogenic wild-type and attenuated . Typhimurium strains. We reveal differential essential pathways between strains and provide a direct link between iron starvation, DNA synthesis, and bacterial membrane integrity.IMPORTANCE is an important clinical pathogen that causes a high number of deaths and is increasingly resistant to antibiotics. Importantly, is used widely as a model to understand host responses to infection. Understanding how Salmonella survives is important for the design of new vaccines to combat this pathogen. Live attenuated vaccines have been used clinically for decades. A widely used mutation, , is thought to attenuate by restricting the ability of the bacterium to access particular amino acids. Here we show that this mutation limits the ability of to acquire iron. These observations have implications for the interpretation of many previous studies and for the use of in vaccine development.
是一种全球传播的病原体，每年导致超过 1 亿例感染。由此引发的疾病取决于宿主易感性和感染的血清型。由于血清型鼠伤寒沙门氏菌在小鼠中引起伤寒样疾病，因此该模型被广泛用于阐明感染和宿主反应的各个方面。由于该模型感染的严重性，研究人员通常使用对感染具有抗性或减毒的小鼠菌株。尽管经过了数十年的研究，但感染的许多方面和基础生物学仍未得到很好的理解。在这里，我们使用转座子插入测序技术来研究广泛使用的同源野生型和减毒鼠伤寒沙门氏菌的必需基因组。我们揭示了菌株之间差异的必需途径，并提供了铁饥饿、DNA 合成和细菌膜完整性之间的直接联系。
重要的是，是一种重要的临床病原体，可导致大量死亡，并且对抗生素的耐药性日益增强。重要的是，被广泛用作模型来了解宿主对感染的反应。了解沙门氏菌如何存活对于设计新疫苗来对抗这种病原体非常重要。活减毒疫苗已在临床上使用了数十年。一种广泛使用的突变，被认为通过限制细菌获取特定氨基酸的能力来使细菌减毒。在这里，我们表明该突变限制了细菌获取铁的能力。这些观察结果对许多先前研究的解释以及对疫苗开发中使用的影响。
