The Lon-1 Protease Is Required by Borrelia burgdorferi To Infect the Mammalian Host
| Autor: | Christina Thompson, Charlotte Mason, Shidoya Parrilla, Zhiming Ouyang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Protease La
Virulence Factors medicine.medical_treatment Immunology Mutant Virulence medicine.disease_cause Microbiology Mice Bacterial Proteins Osmotic Pressure medicine Animals Borrelia burgdorferi Mammals Infectivity Lyme Disease Mutation Protease biology Gene Expression Regulation Bacterial biology.organism_classification Molecular Pathogenesis Phenotype Infectious Diseases Host-Pathogen Interactions bacteria Parasitology Disease Susceptibility rpoS |
| Zdroj: | Infect Immun |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | Borrelia burgdorferi encodes a functional homolog of canonical Lon protease termed Lon-2. In addition, B. burgdorferi encodes a second Lon homolog called Lon-1. Recent studies suggest that Lon-1 may function differently from the prototypical Lon protease. However, the function of Lon-1 in B. burgdorferi biology remains virtually unknown. Particularly, the contribution of Lon-1 to B. burgdorferi fitness and infection remains hitherto unexplored. Herein, we show that Lon-1 plays a critical role for the infection of B. burgdorferi in a mammalian host. We found that lon-1 was highly expressed during animal infection, implying an important function of this protein in bacterial infection. We further generated a lon-1 deletion mutant and an isogenic complemented strain. Relative to that of the wild-type strain, the infectivity of the mutant was severely attenuated in a murine infection model. Our data also showed that the mutant displayed growth defects in regular BSK-II medium. Furthermore, bacterial resistance to osmotic stress was markedly reduced when lon-1 was inactivated. When exposed to tert-butyl hydroperoxide, survival of the lon-1 mutant was impaired. In addition, production of several virulence factors, such as BosR, RpoS, and OspC, was elevated in the mutant. These phenotypes were restored when the lon-1 mutation was complemented. Finally, we created a lon-1(S714A) mutant and found that this mutant failed to infect mice, suggesting that the proteolytic activity of Lon-1 is essential for bacterial infection. Taken together, these results demonstrate that Lon-1 is required by B. burgdorferi to infect animal hosts and to cope with environmental stresses. |
| Databáze: | OpenAIRE |
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