Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Epithelial Cells Are Less Tolerant to Infection by Staphylococcus aureus

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway and provides reducing energy to all cells by maintaining redox balance. The most common clinical manifestations in patients with G6PD deficiency are neonatal jaundice and acute hemolytic anemia. The effects of microbial infection in patients with G6PD deficiency primarily relate to the hemolytic anemia caused by Plasmodium or viral infections and the subsequent medication that is required. We are interested in studying the impact of bacterial infection in G6PD-deficient cells. G6PD knock down A549 lung carcinoma cells, together with the common pathogen Staphylococcus aureus, were employed in our cell infection model. Here, we demonstrate that a lower cell viability was observed among G6PD-deficient cells when compared to scramble controls upon bacterial infection using the MTT assay. A significant increase in the intracellular ROS was detected among S. aureus-infected G6PD-deficient cells by observing dichlorofluorescein (DCF) intensity within cells under a fluorescence microscope and quantifying this signal using flow cytometry. The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. A higher expression level of the intrinsic apoptotic initiator caspase-9, as well as the downstream effector caspase-3, was detected by Western blotting analysis of G6PD-deficient cells following bacterial infection. In conclusion, we propose that bacterial infection, perhaps the secreted S. aureus α-hemolysin in this case, promotes the accumulation of intracellular ROS in G6PD-deficient cells. This would trigger a stronger apoptotic activity through the intrinsic pathway thereby reducing cell viability when compared to wild type cells.

Subversion of Schwann Cell Glucose Metabolism by Mycobacterium leprae

“…Some of these variations are relatively frequent among human population due to the positive impact on a large number of pathogens, conferring natural resistance against Chlamydia trachomatis and Plasmodium falciparum infections (10,11). On the other hand, the PPP is related to increased cellular tolerance to Staphylococcus aureus and Helicobacter pylori (12,13).…”

Prevalence of glucose-6-phosphate dehydrogenase deficiency in Cameroonian blood donors

“…White blood cells also utilize NADPH-regulated pathways (among others) that contribute to the bactericidal respiratory burst. Prior studies have shown that leukocytes or neutrophils from patients with severe (class I) G6PD deficiency have decreased reactive oxygen species (ROS) production, potentially contributing to increased susceptibility to infectious disease [24, 25]. Supporting this mechanism, Siler et al showed that in three siblings with severe G6PD deficiency, there was reduced NADPH oxidase activity in their granulocytes and reduced NETosis, contributing to susceptibility to bacterial infection [26].…”

G6PD Deficiency Does Not Enhance Susceptibility for Acquiring Helicobacter pylori Infection in Sardinian Patients

“…Several studies indicated that G6PD deficiency in leukocytes can result in chronic granulomatous disease with impaired host defense mechanisms against bacterial or fungal infection [ 30 , 31 ]. For example G6PD-deficient epithelial cells in vitro showed a reduced tolerance to Staphylococcus aureus [ 18 ].…”