Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa.
Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa.
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噬菌体耐药性的表征及其对铜绿假单胞菌中细菌适应性的影响。
DOI：
10.1128/spectrum.02072-22
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发表时间：
2022-10-26
影响因子：
3.7
通讯作者：
Tan, Demeng
中科院分区：
文献类型：
--
作者：
Li, Na;Zeng, Yigang;Wang, Mengran;Bao, Rong;Chen, Yu;Li, Xiaoyu;Pan, Jue;Zhu, Tongyu;Hu, Bijie;Tan, Demeng
抗生素耐药性的出现和蔓延对环境和健康构成严重挑战。噬菌体疗法作为一种具有巨大潜力的对抗抗生素耐药性的替代方法已经引起了人们的注意。然而，噬菌体治疗的障碍之一是噬菌体抗性，并且它可以通过基因突变获得，随后是表型变异的后果。因此，了解噬菌体-宿主相互作用的机制将为我们提供如何优化噬菌体治疗的更多细节。在这项研究中，分离出三种裂解性噬菌体（phipa 2，phipa 4和phipa 10），以研究铜绿假单胞菌的噬菌体抗性和潜在的适应性权衡。具体地，在噬菌体抗性突变体phipa 2-R和phipa 4-R中，赋予抗性的突变发生在基因pilT和pilB中，这两个基因对于IV型皮利（T4 P）生物合成都是必需的。在噬菌体抗性突变体phipa 10-R中，观察到约294 kb的大染色体缺失，包括hmgA（尿黑酸1，2-双加氧酶）和galU（UTP-葡萄糖-1-磷酸尿苷酰转移酶）基因，并赋予噬菌体phipa 10抗性。此外，我们展示了这些抗噬菌体突变中相关权衡的例子，例如，运动性受损、生物膜形成减少和抗生素敏感性增加。总的来说，我们的研究揭示了耐药性介导的基因突变及其多效性表型，进一步强调了噬菌体-宿主相互作用的令人印象深刻的复杂性和多样性，以及它们在控制这种重要病原体中的细菌性疾病时所带来的挑战。重要性对抗噬菌体耐药性是噬菌体治疗面临的主要挑战之一。为了克服这一挑战，需要有关噬菌体-宿主相互作用机制的详细信息来了解细菌的进化过程。在这项研究中，我们确定了突变的关键步骤IV型皮利（T4 P）和O-抗原生物合成导致噬菌体抗性，并提供了新的证据，噬菌体捕食如何对宿主表型和健身的变化。总之，我们的研究结果增加了关于噬菌体-宿主相互作用以及它们如何调节假单胞菌细胞行为的不同方面的进一步基础知识。
The emergence and spread of antibiotic resistance pose serious environmental and health challenges. Attention has been drawn to phage therapy as an alternative approach to combat antibiotic resistance with immense potential. However, one of the obstacles to phage therapy is phage resistance, and it can be acquired through genetic mutations, followed by consequences of phenotypic variations. Therefore, understanding the mechanisms underlying phage-host interactions will provide us with greater detail on how to optimize phage therapy. In this study, three lytic phages (phipa2, phipa4, and phipa10) were isolated to investigate phage resistance and the potential fitness trade-offs in Pseudomonas aeruginosa. Specifically, in phage-resistant mutants phipa2-R and phipa4-R, mutations in conferring resistance occurred in genes pilT and pilB, both essential for type IV pili (T4P) biosynthesis. In the phage-resistant mutant phipa10-R, a large chromosomal deletion of ~294 kb, including the hmgA (homogentisate 1,2-dioxygenase) and galU (UTP–glucose-1-phosphate uridylyltransferase) genes, was observed and conferred phage phipa10 resistance. Further, we show examples of associated trade-offs in these phage-resistant mutations, e.g., impaired motility, reduced biofilm formation, and increased antibiotic susceptibility. Collectively, our study sheds light on resistance-mediated genetic mutations and their pleiotropic phenotypes, further emphasizing the impressive complexity and diversity of phage-host interactions and the challenges they pose when controlling bacterial diseases in this important pathogen. IMPORTANCE Battling phage resistance is one of the main challenges faced by phage therapy. To overcome this challenge, detailed information about the mechanisms of phage-host interactions is required to understand the bacterial evolutionary processes. In this study, we identified mutations in key steps of type IV pili (T4P) and O-antigen biosynthesis leading to phage resistance and provided new evidence on how phage predation contributed toward host phenotypes and fitness variations. Together, our results add further fundamental knowledge on phage-host interactions and how they regulate different aspects of Pseudomonas cell behaviors.
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预言919TP及其颤音霍乱宿主之间的相互作用：GMD突变对噬菌体抗性，细胞自动聚集和运动的影响。
DOI：
10.3390/v13122342
发表时间：
2021-11-23
期刊：
Viruses
影响因子：
--
作者：
Li N;Zeng Y;Hu B;Zhu T;Svenningsen SL;Middelboe M;Tan D
通讯作者：
Tan D
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
2.8
作者：
Chiang, Poney;Sampaleanu, Liliana M.;Burrows, Lori L.
通讯作者：
Burrows, Lori L.
影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.
影响因子：
11
作者：
Fernandez, Lucia;Gutierrez, Diana;Rodriguez, Ana
通讯作者：
Rodriguez, Ana