Group A Streptococcus (GAS) causes a broad variety of infections of the throat and skin in addition to invasive diseases. Infection with GAS can also lead to life-threatening postinfection sequelae such as glomerulonephritis or acute rheumatic fever. Although GAS is usually considered an extracellular pathogen, these bacteria can be internalized by cultured epithelial cells, and have been found inside pharyngeal cells of infected patients. Currently the role of GAS internalization during infection and disease is unclear; however, it may play a role in several aspects of infection. Internalization may provide a protective niche for the bacteria, sequestered from both the immune response and antibiotic treatment. Additionally, internalization may explain the high rate of carriers, who possess GAS in their pharynx but do not develop pharyngitis. The experiments designed here set out to understand how the secreted toxins of GAS promote bacterial survival and potential release following internalization by epithelial cells. An inducible expression system will be used to separate the functions of these toxins when expressed by extracellular or intracellular bacteria, and explain how production of these toxins by internalized GAS affects the infected cells. The expression of these toxins during infection will also be investigated to determine if they are upregulated following internalization. This work will elucidate the mechanisms that promote bacterial survival and help to determine the role and importance of internalization during infection. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI074229-01A1
Application #
7408465
Study Section
Special Emphasis Panel (ZRG1-F13-P (20))
Program Officer
Rubin, Fran A
Project Start
2008-02-01
Project End
2010-01-31
Budget Start
2008-02-01
Budget End
2009-01-31
Support Year
1
Fiscal Year
2008
Total Cost
$46,826
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Logsdon, Lauren K; Hakansson, Anders P; Cortes, Guadalupe et al. (2011) Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus. MBio 2:e00332-10