Pseudomonas aeruginosa elongation factor-Tu (EF-Tu) is an immunogenic protective protein antigen
Dina A Moustafa1, Emma Lou2, Morgan E Schafer-Kestenman1
1Emory-Children's Cystic Fibrosis Center, Division of Pulmonary, Asthma, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Abstract:
Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that infects immunocompromised individuals, especially in the hospital setting. This bacterium is an important pathogen in people with weakened immune systems, injuries, and other underlying physiologic dysfunctions. P. aeruginosa is responsible for up to 20 % of all hospital-acquired pneumonias. It is one of the major causes of nosocomial infections and has been noted to be one of the most common bacteria co-infecting patients with COVID-19 or causing super-infections following COVID-19 infections. Despite improvements in antimicrobial therapy and hospital care, P. aeruginosa bacteremia and pneumonia remain fatal in about 30 % of cases. P. aeruginosa is also the leading cause of chronic life-threatening lung infections in cystic fibrosis patients. This bacterium is naturally antibiotic resistant, and infections are notoriously difficult to treat once established, with no vaccine available. We have previously shown that elongation factor-Tu (EF-Tu), a protein best known for its role in protein synthesis, is surface exposed on P. aeruginosa. As this protein is highly expressed, evolutionally conserved, and essential, we hypothesized it would make a good vaccine target. In this study, we found that P. aeruginosa EF-Tu is immunogenic in people, and that mice can develop an immune response following immunization with recombinant P. aeruginosa EF-Tu. Furthermore, immunized mice were protected from subsequent P. aeruginosa pneumonia and transfer of this vaccine antisera to naïve mice resulted in decreased colonization. Altogether these findings support the consideration of EF-Tu as a new vaccine candidate against P. aeruginosa.
Insights
Pseudomonas aeruginosa infections are difficult to treat due to antibiotic resistance. Researchers found that targeting the elongation factor-Tu (EF-Tu) protein shows promise as a new vaccine candidate against this pathogen.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen causing severe hospital-acquired infections, including pneumonia and bacteremia, with high fatality rates.
- This bacterium is a leading cause of chronic lung infections in cystic fibrosis patients and exhibits natural antibiotic resistance, complicating treatment.
- No vaccine is currently available for P. aeruginosa, highlighting the need for novel preventative strategies.
Purpose of the Study:
- To evaluate the potential of elongation factor-Tu (EF-Tu), a surface-exposed protein of P. aeruginosa, as a vaccine target.
- To determine if EF-Tu is immunogenic and if antibodies against it can provide protection against P. aeruginosa infection.
Main Methods:
- Assessed the immunogenicity of P. aeruginosa EF-Tu in humans and mice.
- Immunized mice with recombinant P. aeruginosa EF-Tu and challenged them with the bacteria to evaluate protection against pneumonia.
- Transferred antisera from immunized mice to naive mice to assess the impact on bacterial colonization.
Main Results:
- P. aeruginosa EF-Tu was found to be immunogenic in humans, and mice developed an immune response after immunization.
- Mice immunized with EF-Tu showed protection against subsequent P. aeruginosa pneumonia.
- Passive transfer of vaccine antisera reduced bacterial colonization in naive mice.
Conclusions:
- P. aeruginosa EF-Tu is a viable vaccine candidate.
- Targeting EF-Tu offers a promising new strategy for developing a vaccine against P. aeruginosa infections.
- Further research into EF-Tu-based vaccines is warranted to combat difficult-to-treat P. aeruginosa infections.
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