Enhancement of ATP Levels and Glucose Metabolism during an Infection by Chlamydia

Abstract

The Chlamydia species are obligate intracellular bacteria that proliferate only within the infected cell. Since the extracellular bacteria are metabolically inert and there are no cell-free systems for characterizing Chlamydia metabolism, we studied metabolic changes related to ATP synthesis and glycolysis in HeLa cells infected with Chlamydia psittaci during the course of the 2-day infection cycle using noninvasive 31 P and 13 C NMR methods. We find that the infection stimulates ATP synthesis in the infected cell, with a peak of ATP levels occurring midway through the infection cycle, when most of the metabolically active bacteria are proliferating. The infection also stimulates synthesis of glutamate with a similar time course as for ATP. The stimulation is apparently due to an enhancement in glucose consumption by the infected cell, which also results in an increased rate of lactate production and glutamate synthesis as well as higher glycogen accumulation during the infection. Concurrently, infection leads to an increase in the expression of the glucose transporter, GLUT-1, on HeLa cells, which may account for the enhanced glucose consumption. The chlamydiae are thus able to stimulate glucose transport in the host cell sufficiently to compensate for the extra energy load on the cell represented by the infection.Chlamydia species are causative agents of conjunctivitis and pneumonia, and they are recognized as the leading cause of bacterially acquired sexually transmitted infections. On repeated exposure, the consequences can be blinding trachoma or sequelae from sexually transmitted infection, such as epididymitis or pelvic inflammatory diseases, ectopic pregnancy, or tubal infertility (1, 2). Despite the clinical importance of these infections, the biology and biochemistry of Chlamydia infection remains poorly understood.The chlamydiae are obligate intracellular bacteria that proliferate only within the infected host cell. In line with its requirement for host cell metabolites for survival, Chlamydia exists in two developmental states, elementary bodies (EBs) 1 and reticulate bodies (RBs). EBs represent the metabolically inactive, infectious form of the bacteria, and they are internalized into host cells within membrane-bound vacuoles that avoid fusion with host-cell lysosomes (3). Within 6 -10 h after internalization, the EBs differentiate into the metabolically active RBs. This transformation triggers DNA, RNA, and protein synthesis in the RBs, which proliferate in the growing vacuole and produce up to a thousand progeny. Lipids from the transGolgi network are transported to this membrane (4), and the bacteria contribute their own proteins to the inclusion membrane (5). An intimate association thus exists between the bacteria and the host, but the lack of molecular tools in the field has made further characterization of the association difficult. After approximately 2 days of infection, RBs differentiate back into EBs, and a new infection cycle can begin.Chlamydia trachomatis grows well in cytoplasts (enuc...

Closing in on Chlamydia and its intracellular bag of tricks

“…The stimulation is caused by an increase in the rate of glucose consumption by the infected cell, which also results in increased lactate production and glycogen accumulation. Finally, infection increases surface expression of a glucose transporter on infected cells, which could thus lead to all the other metabolic modifications observed (Ojcius et al, 1998b). These results may not be surprising, however, as increased host cell glucose metabolism has been reported following infection by viruses (Sorbara et al, 1996), and may reflect a host stress response.…”

“…This issue was addressed by studying the effect of C. psittaci strain Guinea Pig Inclusion Conjunctivitis (GPIC) infection on the energy metabolism in infected cells using non-invasive NMR (Ojcius et al, 1998b). The ATP concentration in infected cells increases significantly halfway through infection, decreasing later.…”

Effect of Chlamydia pneumoniae on Cellular ATP Content in Mouse Macrophages: Role of Toll-Like Receptor 2

“…In a study of Wang et al, infection with either C. pneumoniae or Chlamydia trachomatis was shown to decrease ATP synthesis in myocytes, which was accompanied by other indicators of chlamydial cell damage (25). In contrast, Ojcius et al observed a marked increase in several metabolites involved in energy metabolism, including ATP, and the peak ATP levels occurred midway in the infectious cycle (18). In the current study we demonstrated that C. pneumoniae increases the content of ATP in mouse macrophages.…”

Effect of host fatty acid-binding protein and fatty acid uptake on growth of Chlamydia trachomatis L2

“…One of the chlamydial strategies to maintain adequate supplies of these materials from the host cells to chlamydial vacuoles is to enhance the uptake of these molecules by the infected host cells. Similarly to the chlamydial strategy for acquisition of fatty acids as demonstrated in the current study, chlamydiae maintain the supply of glucose, another major carbon source, by increasing both glucose transporter expression and glucose uptake in the infected cells (Ojcius et al, 1998). Both glucose transporters and FABPs are highly conserved tools for eukaryotic cells from different tissue types of all eukaryotic species to maintain the supply of carbon sources.…”