Implication of Glycerol and Phospholipid Transporters in Mycoplasma pneumoniae Growth and Virulence

Abstract

Mycoplasma pneumoniae, the causative agent of atypical pneumonia, is one of the bacteria with the smallest genomes that are nonetheless capable of independent life. Because of their longstanding close association with their human host, the bacteria have undergone reductive evolution and lost most biosynthetic abilities. Therefore, they depend on nutrients provided by the host that have to be taken up by the cell. Indeed, M. pneumoniae has a large set of hitherto unexplored transporters and lipoproteins that may be implicated in transport processes. Together, these proteins account for about 17% of the protein complement of M. pneumoniae. In the natural habitat of M. pneumoniae, human lung epithelial surfaces, phospholipids are the major available carbon source. Thus, the uptake and utilization of glycerol and glycerophosphodiesters that are generated by the activity of lipases are important for the nutrition of M. pneumoniae in its common habitat. In this study, we have investigated the roles of several potential transport proteins and lipoproteins in the utilization of glycerol and glycerophosphodiesters. On the basis of experiments with the corresponding mutant strains, our results demonstrate that the newly identified GlpU transport protein (MPN421) is responsible for the uptake of the glycerophosphodiester glycerophosphocholine, which is then intracellularly cleaved to glycerol-3-phosphate and choline. In addition, the proteins MPN076 and MPN077 are accessory factors in glycerophosphocholine uptake. Moreover, the lipoproteins MPN133 and MPN284 are essential for the uptake of glycerol. Our data suggest that they may act as binding proteins for glycerol and deliver glycerol molecules to the glycerol facilitator GlpF.

Insights into the pathogenesis of Mycoplasma pneumoniae

“…Instead, following permanent adherence via the adherend to the respiratory tract epithelia, M. pneumoniae spreads microtubules and inserts them into host cells, enabling oxygen consumption, use of glucose, absorption of cholesterol, ingestion of amino acids and consumption of nutrients in host cells, causing injury to the host cells (22,23). …”

“…M. pneumoniae also exerts its toxin-like effects through its metabolites, exotoxin and exotoxin-like toxic substances, lipids, lipopolysaccharides and membrane lipoprotein (28). Following the adherence of M. pneumoniae onto the surface of bronchial cells, with the cytoskeleton rearrangement, M. pneumoniae penetrates through the bronchial mucous membranes and releases nuclease and H2O2, which result in swelling, necrosis and a binding of bronchial epithelial cells, slower microvilli movement, structural deformation, and the termination of swinging, thereby inducing the infiltration of lymphocytes, plasma cells and monocytes (22,29). With the lack of superoxide dismutase and catalase in M. pneumoniae , the H2O2 and superoxide groups synthesized by M. pneumoniae , and the endogenous toxic oxygen molecules produced by the host cells, increase the intracellular oxygen pressure in the epithelium, which leads to oxidative stress and subsequent cell death (Fig.…”

Hydrogen sulfide is a novel potential virulence factor of Mycoplasma pneumoniae: characterization of the unusual cysteine desulfurase/desulfhydrase HapE

“…These conditions of life are mirrored in the genome by the strongly reduced number of genes encoding regulatory proteins, and by the limited amounts of carbon sources that can be utilized by M. pneumoniae. Among the few catabolic pathways are glycolysis for the utilization of glucose and fructose and the pathway for the degradation of glycerophospholipids by a dedicated phosphodiesterase and the subsequent utilization of glycerol-3-phosphate (Hames et al, 2009;Schmidl et al, 2011;Großhennig et al, 2013).…”

Catalase Enhances Growth and Biofilm Production of Mycoplasma pneumoniae

“…Brennan and Feinstein showed that catalase activity in mice was essential to initially fight off infection caused by the murine respiratory pathogen Mycoplasma pulmonis but also enhanced the survival of the microorganisms later in the infection, suggesting a balance between the catalase-producing host and the peroxide-producing pathogen [8]. Like M. pulmonis , the human respiratory pathogen M. pneumoniae lacks catalase but produces H 2 O 2 through pathways utilizing glycerol or glycerophosphocholine [4,9]. …”