Mycoplasma pneumoniae

Mycoplasma pneumoniae is a very small bacterium in the class Mollicutes.It is a human pathogen that causes the disease mycoplasma pneumonia, a form of atypical bacterial pneumonia related to cold agglutinin disease. M. pneumoniae is characterized by the absence of a peptidoglycan cell wall and resulting resistance to many antibacterial agents. The persistence of M. pneumoniae infections even after treatment is associated with its ability to mimic host cell surface composition. In 1898, Nocard and Roux were the first to isolate a mycoplasma species in culture from bovine; however, it was not until 1944 when Mycoplasma pneumoniae, known then as Eaton agent or Eaton's agent, was isolated and described from a patient with primary atypical pneumonia. Initially M. pneumoniae was considered as a virus rather than a bacterium, when Eaton and colleagues cultured the causative agent of human primary atypical pneumonia (PAP) or 'walking pneumonia'. The terms 'walking pneumonia' and 'atypical pneumonia' were coined to describe the unresponsiveness of pneumonia inducing M. pneumoniae infections to antibiotics like penicillin. Eaton's agent could be grown in chicken embryos and passed through a filter that excluded normal bacteria. Eaton suggested the possibility that the disease was caused by a mycoplasma, but the agent did not grow on the standard pleuropneumonia-like organism (PPLO) media of the time. These observations led to the conclusion that the causative agent of PAP was a virus. Researchers at that time showed that the cultured agent could induce disease in experimentally infected cotton rats and hamsters. In spite of controversy whether the researchers had truly isolated the causative agent of PAP (based largely on the unusual immunological response of patients with PAP), in retrospect their evidence along with that of colleagues and competitors appears to have been quite conclusive. There were reports linking Eaton agent to the PPLOs or mycoplasmas, well known then as parasites of cattle and rodents, due to sensitivity to antimicrobials. Studies that followed until 1963 determined that Eaton’s agent was a bacterium that caused human lower respiratory tract infections. The term mycoplasma (mykes meaning fungus, and plasma, meaning formed) is derived from the fungal-like growth of some mycoplasma species. The mycoplasmas were classified as Mollicutes (“mollis”, meaning soft and “cutis”, meaning skin) in 1960 due to their small size and genome, lack of cell wall, low G+C content and unusual nutritional needs. M. pneumoniae has also been designated as an arginine nonfermenting species. Mycoplasmas are further classified by the sequence composition of 16s rRNA. All mycoplasmas of the pneumoniae group possess similar 16s rRNA variations unique to the group, of which M. pneumoniae has a 6.3% variation in the conserved regions, that suggest mycoplasmas formed by degenerative evolution from the gram-positive eubacterial group that includes bacilli, streptococci, and lactobacilli. M. pneumoniae is a member of the family Mycoplasmataceae and order Mycoplasmatales. Mycoplasmas, are among the smallest self-replicating organisms, are parasitic species that lack a cell wall and periplasmic space, have reduced genomes, and limited metabolic activity. Mycoplasma pneumoniae cells have an elongated shape that is approximately 0.1–0.2 µm (100-200 nm) in width and 1-2 µm (1000-2000 nm) in length. The extremely small cell size means they are incapable of being examined by light microscopy; a stereomicroscope is required for viewing the morphology of M. pneumoniae colonies, which are usually less than 100 µm in length. The inability to synthesize a peptidoglycan cell wall is due to the absence of genes encoding its formation and results in an increased importance in maintenance of osmotic stability to avoid desiccation. The lack of a cell wall also calls for increased support of the cell membrane(reinforced with sterols), which includes a rigid cytoskeleton composed of an intricate protein network and, potentially, an extracellular capsule to facilitate adherence to the host cell. M. pneumoniae are the only bacterial cells that possess cholesterol in their cell membrane (obtained from the host) and possess more genes that encode for membrane lipoprotein variations than other mycoplasmas, which are thought to be associated with its parasitic lifestyle. M. pneumoniae cells also possess an attachment organelle, which is used in the gliding motility of the organism by an unknown mechanism. Sequencing of the M. pneumoniae genome in 1996 revealed it is 816,394 bp in size. The genome contains 687 genes that encode for proteins, of which about 56.6% code for essential metabolic enzymes; notably those involved in glycolysis and organic acid fermentation. M. pneumoniae is consequently very susceptible to loss of enzymatic function by gene mutations, as the only buffering systems against functional loss by point mutations are for maintenance of the pentose phosphate pathway and nucleotide metabolism. Loss of function in other pathways is suggested to be compensated by host cell metabolism. In addition to the potential for loss of pathway function, the reduced genome of M. pneumoniae outright lacks a number of pathways, including the TCA cycle, respiratory electron transport chain, and biosynthesis pathways for amino acids, fatty acids, cholesterol and purines and pyrimidines. These limitations make M. pneumoniae dependent upon import systems to acquire essential building blocks from their host or the environment that cannot be obtained through glycolytic pathways.Along with energy costly protein and RNA production, a large portion of energy metabolism is exerted to maintain proton gradients (up to 80%) due to the high surface area to volume ratio of M. pneumoniae cells. Only 12 – 29% of energy metabolism is directed at cell growth, which is unusually low for bacterial cells, and is thought to be an adaptation of its parasitic lifestyle. Unlike other bacteria, M. pneumoniae uses the codon UGA to code for tryptophan rather than using it as a stop codon. Mycoplasma pneumoniae grows exclusively by parasitizing mammals. Reproduction, therefore, is dependent upon attachment to a host cell. According to Waite and Talkington, specialized reproduction occurs by “binary fission, temporally linked with duplication of its attachment organelle, which migrates to the opposite pole of the cell during replication and before nucleoid separation”. Mutations that affect the formation of the attachment organelle not only hinder motility and cell division, but also reduce the ability of M. pneumoniae cells to adhere to the host cell. Mycoplasma pneumoniae parasitizes the respiratory tract epithelium of humans. Adherence to the respiratory epithelial cells is thought to occur via the attachment organelle, followed by evasion of host immune system by intracellular localization and adjustment of the cell membrane composition to mimic the host cell membrane.