期刊
INFECTION AND IMMUNITY
卷 88, 期 3, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00762-19
关键词
Acinetobacter; manganese; reactive oxygen species; pathogenesis
资金
- NIH [R01 AI101171]
- American Heart Association [15PRE25060007]
- Public Health Service award from National Institute of General Medical Studies for the Vanderbilt Medical Scientist Training Program [T32 GM07347]
- P.E.O. Scholars Award
- [T32HL094296]
Acinetobacter baumannii is an emerging opportunistic pathogen that primarily infects critically ill patients in nosocomial settings. Because of its rapid acquisition of antibiotic resistance, infections caused by A. baumannii have become extremely difficult to treat, underlying the importance of identifying new antimicrobial targets for this pathogen. Manganese (Mn) is an essential nutrient metal required for a number of bacterial processes, including the response to oxidative stress. Here, we show that exogenous Mn can restore A. baumannii viability in the presence of reactive oxygen species (ROS). This restoration is not dependent on the high-affinity Nramp family Mn transporter, MumT, as a Delta mumT mutant is no more sensitive to hydrogen peroxide (H2O2) killing than wild-type A. baumannii. However, mumR, which encodes the transcriptional regulator of mumT, is critical for growth and survival in the presence of H2O2, suggesting that MumR regulates additional genes that contribute to H2O2 resistance. RNA sequencing revealed a role for mumR in regulating the activity of a number of metabolic pathways, including two pathways, phenylacetate and gamma-aminobutyric acid catabolism, which were found to be important for resisting killing by H2O2. Finally, Delta mumR exhibited reduced fitness in a murine model of pneumonia, indicating that MumR-regulated gene products are crucial for protection against the host immune response. In summary, these results suggest that MumR facilitates resistance to the host immune response by activating a transcriptional program that is critical for surviving both Mn starvation and oxidative stress.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据