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A Tandem Liquid Chromatography–Mass Spectrometry-based Approach for Metabolite Analysis of Staphylococcus aureus
Published on: March 28, 2017
CorA2-mediated magnesium transport is essential for stress adaptation and virulence of Streptococcus agalactiae
Jiayi Liu1, Fengyang Li1, Yong-An Zhang2,3
1Hubei Hongshan Laboratory, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China.
Abstract:
Magnesium (Mg2+) homeostasis is critical for bacterial survival and virulence. Streptococcus agalactiae is a major piscine and mammalian pathogen, yet the molecular mechanisms governing its Mg2+ acquisition remain undefined. Here, we identify and characterize CorA2 as an essential Mg2+ transporter in a hypervirulent S. agalactiae strain HN016. Through biochemical and genetic assays including a corA2 deletion mutant (ΔcorA2), a complemented strain, and structure-guided point mutants (GGGG gain of function and D206K loss of function), we demonstrate that CorA2 is essential for Mg2+ uptake. CorA2 deficiency severely impaired bacterial growth under Mg2+ limitation and heightened susceptibility to host-mimicking stresses, including oxidative stress, acid stress, nitrosative stress, and metal ion toxicity. The ΔcorA2 mutant was markedly compromised in resisting phagocytosis and surviving within macrophages. Intriguingly, while the mutant exhibited enhanced adhesion to and invasion of host cells, its capacity to inflict damage was drastically reduced. In a tilapia infection model, the ΔcorA2 strain showed severe attenuation, with significantly reduced mortality (53.3% versus 93.3% in WT) and systemic bacterial burden. Our findings establish that CorA2-mediated magnesium homeostasis is essential for S. agalactiae to overcome host immune defenses and establish a systemic infection, highlighting CorA2 as a potential target for developing novel anti-infective strategies against this pathogen.
Insights
Magnesium transporter CorA2 is essential for Streptococcus agalactiae survival and virulence. Disrupting CorA2 impairs bacterial growth and resistance to host defenses, making it a potential target for new anti-infective strategies.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Magnesium (Mg2+) homeostasis is vital for bacterial survival and virulence.
- Streptococcus agalactiae is a significant pathogen in fish and mammals, but its Mg2+ uptake mechanisms are unknown.
Purpose of the Study:
- To identify and characterize the Mg2+ transporter in Streptococcus agalactiae.
- To investigate the role of this transporter in bacterial virulence and host-pathogen interactions.
Main Methods:
- Genetic analysis using a corA2 deletion mutant (ΔcorA2) and structure-guided point mutants.
- Biochemical assays to assess Mg2+ uptake and bacterial growth under stress conditions.
- In vitro assays for phagocytosis resistance, macrophage survival, host cell adhesion/invasion, and in vivo tilapia infection model.
Main Results:
- CorA2 was identified as an essential Mg2+ transporter in S. agalactiae HN016.
- ΔcorA2 mutants showed impaired growth under Mg2+ limitation and increased susceptibility to host-mimicking stresses.
- The mutant was less resistant to phagocytosis and macrophage survival but showed enhanced adhesion and invasion.
- In vivo, the ΔcorA2 strain was significantly attenuated in a tilapia infection model, with reduced mortality and bacterial burden.
Conclusions:
- CorA2-mediated magnesium homeostasis is crucial for S. agalactiae virulence.
- This transporter is essential for overcoming host immune defenses and establishing systemic infections.
- CorA2 represents a promising target for developing novel anti-infective therapies against S. agalactiae.
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