Undergraduate Honors Theses

Thesis Defended

Spring 2011

Document Type

Thesis

Department

Molecular, Cellular, & Developmental Biology

First Advisor

Dr. Corrella Detweiler

Abstract

Salmonella enterica serotype Typhimurium (STm) is a Gram-negative bacterial pathogen that causes chronic infection in mammals. During chronic infections, STm preferentially reside in hemophagocytic macrophages (HMs). HMs are a unique type of macrophage that engulf and degrade viable cells of the hematopoietic lineage, such as erythrocytes. Heme, a major component of erythrocyte hemoglobin, is degraded by the host enzyme heme oxygenase-1 (HO-1) resulting in free iron. It is unclear how STm preferentially replicates in HMs, however, we hypothesize that free iron originating from degrading erythrocytes promotes STm replication. To examine if iron promotes STm replication, STm was grown in the presence of degraded erythrocytes and replication was monitored by growth curves. In minimal media, STm replication was augmented in the presence of degraded erythrocytes. Additionally, cell culture assays were utilized to determine STm replication in the presence of added iron, an iron chelator, and an HO-1 inhibitor. Supplementing cell culture non-HMs with free iron increased STm replication, while chelating iron in HMs decreased STm replication. Inhibition of HO-1 activity also decreased STm replication in HMs suggesting that products released from heme breakdown enhance STm replication. Collectively, these results demonstrate that free iron released from HO-1-mediated breakdown of heme contributes to STm replication in HMs (Figure 1).

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