pathogenesis of mycoplasma

Since its initial description in the 1940s and eventual elucidation as a highly evolved pathogenic bacterium, Mycoplasma pneumoniae has come to be recognized as a worldwide cause of primary atypical pneumonia. Another characteristic of the genus Mycoplasma is the requirement for sterols in artificial growth media, supplied by serum. Mycoplasma pneumoniaeinfections have a wide spectrum of clinical symptoms and disease manifestations. M. pneumoniae lacks a cell wall, which differentiates it from other pathogenic bacteria [ 1 ]. The small genome of M. pneumoniae and its limited biosynthetic capabilities are responsible for many of the biological characteristics and requirements for complex medium supplementation in order for the organism to be cultivated in vitro. Although recombination-mediated variation of P1 has not been demonstrated, evidence supports the occurrence of this process for a set of genes of unknown function (Dumke et al., 2004; Musatovova et al., 2008). Michelow et al. Mycoplasma pneumoniae cells exhibit a distinct, elongated shape with a tip structure, the attachment organelle, which is directly involved in several aspects of both the pathogenicity and life cycle of the organism (Fig. The attachment organelle of M. pneumoniae itself is a cellular protrusion containing cytoplasm, in which a complex, detergent-insoluble, proteinaceous, electron-dense core is present (Krause & Balish, 2004; Balish, 2006; Balish & Krause, 2006). The bacteria produce a P1 adhesin protein that allows attachment to a receptor on the respiratory tract epithelial cells. Given the prolonged nature of M. pneumoniae infections,it seems likely that a subset of asthmatics may have a chronic infection that induces a Th2-dominant inflammatory response. Search for other works by this author on: Department of Microbiology, Miami University, Oxford, OH, USA, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA, Molecular approaches to diagnosis of pulmonary diseases due to, Role of superoxide anion in host cell injury induced by, Surface localized glyceraldehyde-3-phosphate dehydrogenase of, Cross-reactive anti-galactocerebroside antibodies and, Mycoplasmas: a distinct cytoskeleton for wall-less bacteria, Evaluation of 12 commercial tests and the complement fixation test for, Antibodies to brain and other tissues in cases of, Three cases of central nervous system complications associated with. Antimicrobial management of systemic infections caused by M. pneumoniae that extend beyond the respiratory tract can be difficult, especially in persons who have antibody deficiencies or are otherwise immunocompromised. Additional evidence for molecular mimicry by M. pneumoniae comes from a study in which adherence-inhibiting anti-P1 adhesin monoclonal antibodies showed cross-reactions with intracellular antigens of eukaryotic cell lines in immunofluorescence microscopy experiments. All 12 strains had a C-to-T 785 transition in domain II. Since then, there have been more than 200 publications describing the use of PCR for detection of M. pneumoniae in human infections and characterization of its basic biological features. The best-commercial serological test for individual patient diagnosis depends on the age of the patient, timing of serum collection, whether paired sera are obtained, availability of appropriate, equipment, and experience of the laboratory personnel. Like many other mycoplasmoses of humans and animals, the spectrum of respiratory conditions caused by M. pneumoniae stems from close association between the organism and the epithelial tissue of the host. Some of the pathogens are known to infect various organs of their leaf hopper or psyllid vectors and to multiply in their cells. Subsequent to cytadherence, M. pneumoniae is believed to cause disease in part through generation of peroxide. The frequent occurrence of outbreaks of mycoplasmal infections and lack of protective immunity against reinfection has stimulated research since the early 1960's into vaccine development using animal models and human volunteers. Studies in the distantly related organism Mycoplasma mycoides ssp. Cookies used to make website functionality more relevant to you. mycoides SC have elucidated a correlation between pathogenicity and peroxide formation as a by-product of glycerol metabolism through l--glycerophosphate oxidase (Vilei & Frey, 2001; Pilo et al., 2005). Mycoplasma pneumoniae also produces capsular material that may have a role in cytadherence. In addition, using PCR, these investigators detected the A-to-G mutation in 23 of 94 (24%) PCR-positive oral samples taken from children with respiratory infections. As a result, our understanding of M. pneumoniae's cell biology, mechanisms of cytadherence, disease production, evasion of host defenses, disease transmission, contribution to chronic lung diseases, emergence of antimicrobial resistance, and efficacy of new antimicrobial treatments have improved. The variability of results from comparative studies and concerns for basing diagnosis of acute M. pneumoniae infection on a single serum specimen underscores the need for improved sensitivities and specificities among serological reagents used commercially for detecting acute M. pneumoniae infection (Talkington et al., 2004; Beersma et al., 2005). The main aspects to emphasize are that clinical chemistry and hematological laboratory findings are seldom diagnostic. Mycoplasma pneumoniae bacteria commonly cause mild infections of the respiratory system (the parts of the body involved in breathing). Pathogenesis of Mycoplasma pneumoniae: An update Genus Mycoplasma, belonging to the class Mollicutes, encompasses unique lifeforms comprising of a small genome of 8,00,000 base pairs and the inability to produce a cell wall under any circumstances. Although this picture has been presented as typical, in actuality, family studies have revealed that many individuals never progress to the severe lower respiratory phase of the infection and up to 20% may be asymptomatic (Clyde, 1983). A substantial amount of research has been carried out in recent years to improve understanding of what happens at the subcellular . Abele-Horn M Kautz S Stubenrauch C Leo F Frosch M (, Beersma MF Dirven K Van Dam AP Templeton KE Claas EC Goossens H (, Bernet C Garret M De Barbeyrac B Bebear C Bonnet J (, Bitnun A Ford-Jones E Blaser S Richardson S (, Block S Hedrick J Hammerschlag MR Cassell GH Craft JC (, Broaders SA Hooper WC Phillips DJ Talkington DF (, Chen W Li D Paulus B Wilson I Chadwick VS (, Christie LJ Honarmand S Talkington DF et al. Accordingly, the M. pneumoniae cell volume is <5% of that of a typical bacillus. Superoxide anion produced by M. pneumoniae acts to inhibit catalase in host cells, thereby reducing the enzymatic breakdown of peroxides produced endogenously and by the Mycoplasma rendering the host cell more susceptible to oxidative damage (Almagor et al., 1984). Other advantages are the potential ability to complete the procedure in one day, the possibility of obtaining a positive result sooner after onset of illness than serology, the requirement of only one specimen containing organisms that do not have to be viable, as well as the ability to detect nucleic acid in preserved tissues. They help us to know which pages are the most and least popular and see how visitors move around the site. Of particular interest was the behaviour of Mycoplasma mycoides ssp. Marston BJ, Plouffe JF, File Jr TM, et al. (2004) evaluated nasopharyngeal and oropharyngeal samples obtained from children with serologically proven M. pneumoniae pneumonia and reported that either specimen type was equally effective for detection of the organism using PCR, but combining results form both sites provided the greatest diagnostic yield. Mycoplasmas are not found freely living in nature because they depend on a host cell to supply the necessary nutrients. Mycoplasma bovis (M. bovis) is an etiological agent of bronchopneumonia, mastitis, arthritis, otitis, keratoconjunctivitis, meningitis, endocarditis and other disorders in cattle.It is known to spread worldwide, including countries for a long time considered free of the infection. Mutations in the quinolone resistance determining regions resulted in minimum inhibitory concentrations (MICs) for ciprofloxacin up to 32 g mL1 (Gruson et al., 2005). High-dose steroids have been reported to be useful in treatment of encephalitis in children with complicated M. pneumoniae infection. The close association betweenM. pneumoniaeand the host cells prevents the hosts mucociliary clearance mechanisms from removing the bacterium. Synthetic microbial communities (SynComs) of the human gut: design, assembly, and applications, Galleria mellonella-intracellular bacteria pathogen infection models: the ins and outs, Bacterial virulence regulation through soluble peptidoglycan fragments sensing and response: knowledge gaps and therapeutic potential, The coral microbiome: Towards an understanding of the molecular mechanisms of coral-microbiota interactions, Manipulation of plant metabolism by pathogen effectors: more than just food, About the Federation of European Microbiological Societies, Molecular basis for cytadherence and production of disease, Interaction with host immune cells and autoimmunity, Epidemiology of mycoplasmal respiratory disease, Clinical manifestations of mycoplasmal respiratory disease, Antimicrobial susceptibility testing and treatment, https://doi.org/10.1111/j.1574-6976.2008.00129.x, Receive exclusive offers and updates from Oxford Academic, Copyright 2023 Federation of European Microbiological Societies. This activates the innate immune response and produces local cytotoxic effects. M. pneumoniae lacks a rigid cell wall, allowing it to alter its size and shape to suit its surrounding conditions. Because M. pneumoniae is a mucosal pathogen, IgA is typically produced early in the course of infection. Fermentation of glucose to lactic acid and acetic acid by means of substrate-level phosphorylation mediated by phosphoglyceric acid kinase, pyruvate kinase, and acetate kinase activities is a means of ATP generation; glycerol and some other small carbohydrates may also be metabolized to generate ATP. Unfortunately, as with GBS cases, most cases have been diagnosed only by detection of the presence of antibody to M. pneumoniae with a preceding respiratory illness, so establishment of a causal relationship is difficult. Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP), and the disease usually has a prolonged, gradual onset. Mycoplasma is a genus of bacteria that, like the other members of the class Mollicutes, lack a cell wall around their cell membranes. Practice Essentials. Additionally, it is unclear how a toxin function might relate to its specific binding to surfactant protein A, although it has become clear that numerous proteins of M. pneumoniae and its relatives double as adhesins to host extracellular proteins like fibronectin (Dallo et al., 2002; May et al., 2006) and mucin (Alvarez et al., 2003). Recent studies (Henderson & Jensen, 2006; Seybert et al., 2006) reveal this core to consist of a pair of nonequivalent parallel rods with numerous cross-striations, connected to the tip of the attachment organelle through a terminal button. However, M. pneumoniae macrolide-resistant mutants selected in vitro harbored mutations in other positions of 23S rRNA gene (A2062, E. coli numbering) or in ribosomal proteins L4 and L22 and could be predictive for mutations that will be eventually be observed in clinical strains (Pereyre et al., 2004). Although no correlation between the morphology of the electron-dense core and motility properties was observed among M. pneumoniae relatives (Hatchel & Balish, 2008), it is possible that finer features of the core are involved in the gliding process. Electron microscopy and genome analysis confirm the absence of flagella and pili. Nucleic acid sequence-based amplification (NASBA), which is an isotheramal RNA amplification technique has been applied for the detection of M. pneumoniae (Loens et al., 2002, 2003a, b, 2007, 2008) Initial studies have shown it can be comparable to PCR assays in terms of sensitivity. This property was adapted for use as a diagnostic test to presumptively distinguish M. pneumoniae from other commensal mycoplasmas that are commonly found in the human respiratory tract that do not hemadsorb in this manner. CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. A variety of extrapulmonary invasive manifestations of M. pneumoniae infection have been described, and patients who have compromised immunity, including humoral immunodeficiencies are more likely to suffer these complications (Johnston et al., 1983; Roifman et al., 1986; Gelfand et al., 1993; O'Sullivan et al., 2004). Diagnosis is based on demonstration of the organism on the surface of . Many of these neuroinvasive cases lack the typical pulmonary symptoms and antibody, unlike patients with M. pneumoniae-associated GBS (Christie et al., 2007a, b). Mycoplasma pneumoniae possesses very limited metabolic and biosynthetic activities for proteins, carbohydrates, and lipids. Models have been proposed in which the electron-dense core is the principal source of motor activity, either through rotation (Hegermann et al., 2002) or vibration (Henderson & Jensen, 2006). Positive PCR results in serologically negative persons may be due to an inadequate immune response, early successful antibiotic treatment, or to the collection of specimens before specific antibody synthesis could occur. These include: M. penetrans M. pneumoniae M. urealytium M. hominis M. genitalium M. pirum M. fermentation As parasites, species like M. pneumoniae have to attach to the cell of the host first. Naturally occurring resistance to tetracyclines or fluoroquinolones has never been reported in M. pneumoniae, but in vitro selection of mutants resistant to both drug classes through serial subcultures with increasing concentrations has been successful (Gruson et al., 2005; Degrange et al., 2008). In some cases, IgA is the only antibody class that is positive (Lieberman et al., 2002). Thus far, these efforts have been disappointing and not much has been performed in this field in recent years largely due to, first, the HIV epidemic and, more recently, preoccupation of governmental funding agencies with select agents more useful in bioterrorism. They found an A-to-G transition at position 2063 in domain V of the 23S rRNA gene in nine strains and an A-to-G transition at position 2064 in two strains. The Mycoplasma pneumonia bacterium is . However, the ultimate targets of this pathway, which in other organisms include a transcription factor absent in M. pneumoniae, remain unclear. Among 76 M. pneumoniae strains isolated between 2000 and 2003 in the northern, central, and southern regions of Japan, 13 (17%) were resistant to erythromycin, 12 of which had MICs >256 g mL1 (Matsuoka et al., 2004). The molecular mechanism underlying gliding motility in M. pneumoniae is unclear. Thisattachment is critical to the bacterias survival and ability to infect. Extrapolation of these data nationally provides an estimated number of CAP cases due to M. pneumoniae in hospitalized adults that exceeds 100 000 on an annual basis. Nucleotide sequencing of 23S rRNA gene domains II and V and ribosomal proteins L4 and L22 showed that 10 strains had an A-to-G transition at position 2063 (M. pneumoniae numbering equivalent to 2058 in Escherichia coli numbering), one strain had A-to-C transversion at position 2063, 1 strain showed A-to-G transition at position 2064 and one a C-to-G transversion at position 2617 (M. pneumoniae numbering, or 2611 in E. coli numbering). Thus, bacterial transmission from person to person by airborne droplets only occurs through close contact. Scanning electron micrograph of Mycoplasma pneumoniae cells grown on glass coverslips. As the only observable loss of function in these cells is an approximately threefold reduction in gliding speed, it appears that optimal gliding is necessary for colonization of fully differentiated, mucus-producing tissue. Mycoplasma pneumoniae reduces tetrazolium and this property has been used historically to distinguish it from commensal oropharyngeal mycoplasmas. Mycoplasma have a high affinity for respiratory epithelial cells. A single measurement of IgM may detect an acute infection if the test is performed after at least 7 days following onset; but the result may be negative if the test is performed sooner than this. HPr kinase (HprK) is central in the sensing of carbon metabolites and the regulation of carbon metabolism (Galinier et al., 1998). WhileM. pneumoniae primarily lives on the surface of the respiratory epithelial cells, it can invade tissues and replicate intracellularly. Complement fixation (CF) was the first method developed for serological testing for M. pneumoniae. Gene targets used in various types of PCR assays for M. pneumoniae include 16S rRNA gene, P1 adhesin, an ATPase operon gene, the tuf gene, and repetitive element repMp1, among others (Waites & Talkington, 2004). Type II pneumocyte hyperplasia and diffuse alveolar damage have also been reported. As the genome of M. pneumoniae encodes the same enzyme, and metabolism of glycerol by M. pneumoniae is known to result in peroxide production (Low et al., 1971), it is reasonable to propose that the same metabolic pathway contributes to M. pneumoniae disease. Several studies have been performed in Europe using a variety of IgA assay types (Sillis, 1990; Granstrom et al., 1994; Seggev et al., 1996; Watkins-Riedel et al., 2001; Lieberman et al., 2002; Abele-Horn et al., 2006; Daxboeck et al., 2006) that generally support its use to detect acute infection, especially in older persons. If you do not allow these cookies we will not know when you have visited our site, and will not be able to monitor its performance. Perhaps the most important question arising from the emergence of macrolide-resistant M. pneumoniae in Japan is whether there is an associated clinical implication. Subsequent to cytadherence, M. pneumoniae, remain unclear have a high affinity respiratory! Of clinical symptoms and disease manifestations to a receptor on the surface of body. Be useful in treatment of encephalitis in children with complicated M. pneumoniae is unclear only occurs through close contact nutrients. 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