Deletion of glutaredoxin promotes oxidative tolerance and intracellular infection in Listeria monocytogenes

Abstract

Thiol-disulfide glutaredoxin systems of bacterial cytoplasm favor reducing conditions for the correct disulfide bonding of functional proteins, and therefore were employed by bacteria to defend against oxidative stress. Listeria monocytogenes has been shown to encode a putative glutaredoxin, Grx (encoded by lmo2344), while the underlying roles remain unknown. Here we suggest an unexpected role of L. monocytogenes Grx in oxidative tolerance and intracellular infection. The recombinant Grx was able to efficiently catalyze the thiol-disulfide oxidoreduction of insulin in the presence of DTT as an election donor. Unexpectedly, the deletion of grx resulted in a remarkably increased tolerance and survival ability of this bacteria when exposed to various oxidizing agents, including diamide, and copper and cadmium ions. Furthermore, loss of grx significantly promoted bacterial invasion and proliferation in human epithelial Caco-2 cells and murine macrophages, as well as a notably increasing invasion but not cell-to-cell spread in the murine fibroblasts L929 cells. More importantly, L. monocytogenes lacking the glutaredoxin exhibited more efficient proliferation and recovery in the spleens and livers of the infected mice, and hence became more virulent by upregulating the virulence factors, InlA and InlB. In summary, we here for the first time demonstrated that L. monocytogenes glutaredoxin plays a counterintuitive role in bacterial oxidative resistance and intracellular infection, which is the first report to provide valuable evidence for the role of glutaredoxins in bacterial infection, and more importantly suggests a favorable model to illustrate the functional diversity of bacterial Grx systems during environmental adaption and host infection.

Correlative proteomics identify the key roles of stress tolerance strategies in Acinetobacter baumannii in response to polymyxin and human macrophages

“…In the literature, cold shock protein CspA in Brucella melitensis plays an important role in resistance to acidic and hydrogen peroxide stresses, allowing bacterial replication in J774.A1 murine macrophages [ 49 ]. The thioredoxin superfamily includes both the thioredoxin and glutathione/glutaredoxin systems, and serves as a key antioxidant system through regulation of protein dithiol/disulfide balance [ 50 , 51 ]. It is also involved in DNA and protein repair by transferring reducing equivalents to ribonucleotide reductase, Msr and Dsb systems, as well as regulating the activity of redox-sensitive transcription factors [ 52 ].…”

Comparative pan‐genomic analysis of 51 Renibacterium salmoninarum indicates heterogeneity in the principal virulence factor, the 57 kDa protein

“…Cell exposure to the oxidative conditions created by host neutrophils and macrophages results in the damage of cellular components, including DNA, membrane lipids, and proteins. Consequently, most organisms produce catalases, peroxiredoxins, and oxidoreductases that convert harmful oxidants into harmless products before cellular components are damaged (Sun et al, 2019). In the subcategory for periplasmic stress, R. salmoninarum presented one protein (membrane endopeptidase M50 family).…”

Enhanced stress resistance of Bifidobacterium breve NRBB57 by induction of stress proteins at near-zero growth rates

“…Lastly, four proteins are upregulated in retentostat cells that have a specialised function in oxidative stress response: thioredoxin peroxidase, thioredoxin reductase, ferredoxin and peroxiredoxin. The thioredoxins have several roles in the stress response: reduction of peroxides, protein folding, catalysis of biological thioldisulphide exchange reactions and reduction of oxidised redox sensors and helping in the transcription of genes involved in physiological responses against oxidative stress (Gonzalez et al, 2020;Sun et al, 2019). Peroxiredoxin and ferredoxin scavenge peroxides and other toxic forms of oxygen.…”