Girardo Benjamin, Yue Yinshi, Lockridge Oksana, Bartling Amanda M, Schopfer Lawrence M, Augusto Leonardo, Larson Marilynn A
Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA.
J Bacteriol. 2025 Feb 20;207(2):e0037724. doi: 10.1128/jb.00377-24. Epub 2025 Jan 23.
is one of the most virulent bacterial pathogens known and causes the disease tularemia, which can be fatal if untreated. This zoonotic and intracellular pathogen is exposed to diverse environmental and host stress factors that require an appropriate response to survive. However, the stress tolerance mechanisms used by to persist are not fully understood. To address this aspect, we evaluated the highly conserved niversal tress rotein (Usp) that is encoded by a single-copy gene in , unlike the majority of other bacterial pathogens that produce several to many Usp homologs. We determined that the Usp transcript is unusually stable with a half-life of over 30 minutes, and that transcript and protein levels remained abundant when exposed to low pH, nutrient deprivation, hydrogen peroxide, and paraquat. Of these and other stress conditions evaluated, the Δ mutant only exhibited reduced survival relative to the wild type during stationary phase and exposure to paraquat, a highly toxic compound that generates superoxide anions and other free radicals. Comparison of transcript levels in untreated and paraquat-treated wild type and Δ indicated that Usp contributes to enhanced expression of antioxidant defense genes, and . In summary, the high abundance and stability of Usp provide prompt protection during extended periods of growth arrest and free radical exposure, promoting persistence. We propose that Usp contributes to an adaptive response that prolongs viability and increases the longevity of this zoonotic pathogen in the environment.
is classified as a Tier 1 select agent due to the low infectious dose, ease of transmission, and potential use as a bioweapon. To better understand the stress defense mechanisms that contribute to the ability of this highly virulent pathogen to persist, we evaluated the conserved niversal tress rotein (Usp). We show that Usp is unusually stable and remains abundant, regardless of the stress conditions tested, differing from other bacterial Usp homologs. We also determined that Usp enhances the expression of several critical antioxidant defense genes and increases survival during paraquat exposure and growth arrest. Determining the factors that promote persistence in the environment is needed to prevent tularemia transmission.
是已知的最具毒性的细菌病原体之一，可导致兔热病，若不治疗可能致命。这种人畜共患的细胞内病原体面临各种环境和宿主应激因素，需要做出适当反应才能存活。然而，用于持续存在的应激耐受机制尚未完全了解。为了解决这一方面的问题，我们评估了高度保守的通用应激蛋白（Usp），它由单拷贝基因编码，这与大多数其他产生多个至许多Usp同源物的细菌病原体不同。我们确定该Usp转录本异常稳定，半衰期超过30分钟，并且在暴露于低pH、营养剥夺、过氧化氢和百草枯时，转录本和蛋白质水平仍然丰富。在评估的这些和其他应激条件中，该Δ突变体仅在稳定期和暴露于百草枯（一种产生超氧阴离子和其他自由基的剧毒化合物）期间相对于野生型表现出存活率降低。未处理和经百草枯处理的野生型和Δ中的转录本水平比较表明，Usp有助于增强抗氧化防御基因和的表达。总之，Usp的高丰度和稳定性在长时间生长停滞和自由基暴露期间提供了迅速的保护，促进了持续存在。我们提出，该Usp有助于一种适应性反应，延长这种人畜共患病原体在环境中的生存能力并增加其寿命。
由于其低感染剂量、易于传播以及作为生物武器的潜在用途，被列为一级选择制剂。为了更好地理解有助于这种高毒力病原体持续存在能力的应激防御机制，我们评估了保守的通用应激蛋白（Usp）。我们表明，该Usp异常稳定，并且无论测试的应激条件如何都保持丰富，这与其他细菌Usp同源物不同。我们还确定，该Usp增强了几种关键抗氧化防御基因的表达，并在百草枯暴露和生长停滞期间提高了存活率。确定促进在环境中持续存在的因素对于预防兔热病传播是必要的。
