Project Title

C-reactive protein, antibiotics, and treatment of pneumococcal infection in mice

Authors' Affiliations

Donald N. Ngwa, Department of Biomedical Sciences, College of Medicine, ETSU. Sanjay K. Singh, Department of Biomedical Sciences, College of Medicine, ETSU. Toh B. Gang, Poplar Healthcare, Memphis. Alok Agrawal, Department of Biomedical Sciences, College of Medicine, ETSU.

Location

RIPSHIN MTN. ROOM 130

Start Date

4-4-2018 9:00 AM

End Date

4-4-2018 9:15 AM

Name of Project's Faculty Sponsor

Dr. Alok Agrawal

Faculty Sponsor's Department

Department of Biomedical Sciences

Type

Oral Presentation

Classification of First Author

Graduate Student-Doctoral

Project's Category

Biomedical and Health Sciences

Abstract Text

C-reactive protein (CRP) binds to Streptococcus pneumoniae through the phosphocholine groups present in the cell wall and subsequently activates the complement system to kill the pathogen. To escape the attack of complement, pneumococci recruit a complement inhibitory protein, factor H, on their surface. It has been shown that CRP protects mice against pneumococcal infection only when injected within 2 hours after administering pneumococci. We hypothesized that CRP is not protective when injected at later times because, by then, factor H is recruited by pneumococci. In the current study, we evaluated the protective effects of an engineered CRP molecule (E-CRP) which does not bind to factor H in fluid phase but binds to factor H-coated pneumococci. We found that E-CRP, unlike native CRP, protected mice regardless of the timing of administering E-CRP by drastically reducing bacteremia and increasing survival of mice. Next, we established another murine model of pneumococcal infection using the antibiotic clarithromycin. We found that the combination of E-CRP and clarithromycin was more protective against infection when compared to the protective effects of either E-CRP alone or clarithromycin alone. These findings suggest that the structure of native CRP has to be altered to display its full anti-pneumococcal activity and that CRP and antibiotic act synergistically to protect against pneumococcal infection by decreasing bacteremia. These data also have implications for infections with other bacterial species that use factor H to evade the attack of complement. Additionally, the administration of E-CRP may be therapeutically beneficial to treat infections with antibiotic-resistant bacteria.

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Apr 4th, 9:00 AM Apr 4th, 9:15 AM

C-reactive protein, antibiotics, and treatment of pneumococcal infection in mice

RIPSHIN MTN. ROOM 130

C-reactive protein (CRP) binds to Streptococcus pneumoniae through the phosphocholine groups present in the cell wall and subsequently activates the complement system to kill the pathogen. To escape the attack of complement, pneumococci recruit a complement inhibitory protein, factor H, on their surface. It has been shown that CRP protects mice against pneumococcal infection only when injected within 2 hours after administering pneumococci. We hypothesized that CRP is not protective when injected at later times because, by then, factor H is recruited by pneumococci. In the current study, we evaluated the protective effects of an engineered CRP molecule (E-CRP) which does not bind to factor H in fluid phase but binds to factor H-coated pneumococci. We found that E-CRP, unlike native CRP, protected mice regardless of the timing of administering E-CRP by drastically reducing bacteremia and increasing survival of mice. Next, we established another murine model of pneumococcal infection using the antibiotic clarithromycin. We found that the combination of E-CRP and clarithromycin was more protective against infection when compared to the protective effects of either E-CRP alone or clarithromycin alone. These findings suggest that the structure of native CRP has to be altered to display its full anti-pneumococcal activity and that CRP and antibiotic act synergistically to protect against pneumococcal infection by decreasing bacteremia. These data also have implications for infections with other bacterial species that use factor H to evade the attack of complement. Additionally, the administration of E-CRP may be therapeutically beneficial to treat infections with antibiotic-resistant bacteria.