Document Details

Document Type:   Dissertation
Title:   Characterization of Host-Bacteria Interactions Contributing to Group B Streptococcus Colonization
Author:   Jennifer Marie Smith
College:   Joan C. Edwards School of Medicine
Degree Program:   Biomedical Sciences, Ph.D.
Degree:   Doctor of Philosophy
Committee Director:   Susan H. Jackman, Ph.D.
Document Availability:   Document available for World-Wide access.
Date of Defense:   04/05/02

Group B streptococcus (GBS) is the leading cause of life-threatening bacterial infections during the first three months of life. GBS is also a frequent cause of maternal postpartum infections. Both types of infections stem from maternal vaginal and/or rectal colonization with GBS in the perinatal period. Limited information is available concerning how the colonization process occurs and what role the host immune system may play in the establishment of persistent colonization by GBS. The complex interactions between the immune system and GBS normally should end in clearance of the bacteria. However, since colonization by GBS occurs in a large number of women it can be surmised that the immune defenses are not functioning in a manner consistent with a protective response or that GBS is in some fashion undermining them. Investigations examining interactions between GBS and components of the innate immune system support this hypothesis. Measurement of phagocytosis and respiratory burst capacities revealed that monocytes, in particular, from these women internalize larger quantities of bacteria while the antimicrobial superoxide is shunted to an extracellular location. This data indicated that phagocytes from colonized women might become a protective niche for GBS upon engulfment. Additional data also showed that these same women (GBS-colonized) had significantly increased levels of mannose binding lectin (MBL) in their sera and that high levels of MBL significantly enhanced phagocytic engulfment of GBS. While these data support the idea that the host immune system is not functioning as it normally should to prevent infection and colonization, other data provided evidence that GBS is capable of using components of the immune response to its own benefit. GBS bound interleukin-6 (IL-6) and used the biologically active pro-inflammatory cytokine to enhance its growth and the expression of at least one virulence factor, the C5a-ase. GroEL, a protein implicated in pathogenesis of a number of other bacterial species, was also increased by IL-6 exposure to GBS. Understanding how the immune system and GBS interacts is key to elucidating the mechanisms that underlie the colonization and infection processes as well as may aid in the identification of targets for potential treatment and prevention strategies.  

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