is an important cause of respiratory tract infections in children as well as adults that can range in severity from mild to life-threatening. Over the past several years there has been much new ...information published concerning infections caused by this organism. New molecular-based tests for
detection are now commercially available in the United States, and advances in molecular typing systems have enhanced understanding of the epidemiology of infections. More strains have had their entire genome sequences published, providing additional insights into pathogenic mechanisms. Clinically significant acquired macrolide resistance has emerged worldwide and is now complicating treatment.
susceptibility testing methods have been standardized, and several new drugs that may be effective against this organism are undergoing development. This review focuses on the many new developments that have occurred over the past several years that enhance our understanding of this microbe, which is among the smallest bacterial pathogens but one of great clinical importance.
In recent decades, bacterial cell biology has seen great advances, and numerous model systems have been developed to study a wide variety of cellular processes, including cell division, motility, ...assembly of macromolecular structures, and biogenesis of cell polarity. Considerable attention has been given to these model organisms, which include Escherichia coli, Bacillus subtilis, Caulobacter crescentus, and Myxococcus xanthus. Studies of these processes in the pathogenic bacterium Mycoplasma pneumoniae and its close relatives have also been carried out on a smaller scale, but this work is often overlooked, in part due to this organism's reputation as minimalistic and simple. In this minireview, I discuss recent work on the role of the M. pneumoniae attachment organelle (AO), a structure required for adherence to host cells, in these processes. The AO is constructed from proteins that generally lack homology to those found in other organisms, and this construction occurs in coordination with cell cycle events. The proteins of the M. pneumoniae AO share compositional features with proteins with related roles in model organisms. Once constructed, the AO becomes activated for its role in a form of gliding motility whose underlying mechanism appears to be distinct from that of other gliding bacteria, including Mycoplasma mobile. Together with the FtsZ cytoskeletal protein, motility participates in the cell division process. My intention is to bring this deceptively complex organism into alignment with the better-known model systems.
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. Beyond its ability to cause severe lower respiratory illness and milder upper respiratory symptoms it has become apparent that a wide array of extrapulmonary infectious and postinfectious events may accompany the infections in humans caused by this organism. Autoimmune disorders and chronic diseases such as asthma and arthritis are increasingly being associated with this mycoplasma, which frequently persists in individuals for prolonged periods. The reductive evolutionary process that has led to the minimal genome of M. pneumoniae suggests that it exists as a highly specialized parasitic bacterium capable of residing in an intracellular state within the respiratory tissues, occasionally emerging to produce symptoms. This review includes discussion of some of the newer aspects of our knowledge on this pathogen, characteristics of clinical infections, how it causes disease, the recent emergence of macrolide resistance, and the status of laboratory diagnostic methods.
The atypical bacterial pathogen
is a leading etiological agent of community-acquired pneumonia in humans; infections are often recalcitrant, recurrent and resistant to antibiotic treatment. These ...characteristics suggest a mechanism that facilitates long-term colonization in hosts. In an
setting,
forms biofilms that are unusual in that motility plays no more than a very limited role in their formation and development. Given the unusual nature of
biofilms, open questions remain concerning phenotypes associated with persistence, such as what properties might favour the bacteria while minimizing host damage.
also produces several cytotoxic molecules including community-acquired respiratory distress syndrome (CARDS) toxin, H
S and H
O
, but how it deploys these agents during growth is unknown. Whereas several biochemical techniques for biofilm disruption were ineffective, sonication was required for disruption of
biofilms to generate individual cells for comparative studies, suggesting unusual physical properties likely related to the atypical cell envelope. Nonetheless, like for other bacteria, biofilms were less susceptible to antibiotic inhibition and complement killing than dispersed cells, with resistance increasing as the biofilms matured. CARDS toxin levels and enzymatic activities associated with H
S and H
O
production were highest during early biofilm formation and decreased over time, suggesting attenuation of virulence in connection with chronic infection. Collectively, these findings result in a model of how
biofilms contribute to both the establishment and propagation of
infections, and how both biofilm towers and individual cells participate in persistence and chronic disease.
is an important etiologic agent of non-gonococcal urethritis (NGU), known for chronicity and multidrug resistance, in which biofilms may play an integral role. In some bacterial species capable of ...forming biofilms, extracellular polymeric substances (EPS) composed of poly-
-acetylglucosamine (PNAG) are a crucial component of the matrix. Monosaccharide analysis of
strains revealed high abundance of GlcNAc, suggesting a biofilm-specific EPS. Chromatograms also showed high concentrations of galactose and glucose as observed in other mycoplasma species. Fluorescence microscopy of
biofilms utilizing fluor-coupled lectins revealed differential staining of biofilm structures. Scanning electron microscopy (SEM) showed increasing maturation over time of bacterial "towers" seen in biofilm development. As seen with
, organisms within fully mature
biofilms exhibited loss of cell polarization. Bacteria associated with disrupted biofilms exhibited decreased dose-dependent viability after treatment with antibiotics compared to bacteria with intact biofilms. In addition, growth index analysis demonstrated decreases in metabolism in cultures with disrupted biofilms with antibiotic treatment. Taken together, these data suggest that
biofilms are a contributing factor in antibiotic resistance.
Several mycoplasma species have been shown to form biofilms that confer resistance to antimicrobials and which may affect the host immune system, thus making treatment and eradication of the ...pathogens difficult. The present study shows that the biofilms formed by two strains of the human pathogen Mycoplasma pneumoniae differ quantitatively and qualitatively. Compared with strain UAB PO1, strain M129 grows well but forms biofilms that are less robust, with towers that are less smooth at the margins. A polysaccharide containing N-acetylglucosamine is secreted by M129 into the culture medium but found in tight association with the cells of UAB PO1. The polysaccharide may have a role in biofilm formation, contributing to differences in virulence, chronicity and treatment outcome between strains of M. pneumoniae. The UAB PO1 genome was found to be that of a type 2 strain of M. pneumoniae, whereas M129 is type 1. Examination of other M. pneumoniae isolates suggests that the robustness of the biofilm correlates with the strain type.
Infections with the respiratory pathogen
are often chronic, recurrent and resistant, persisting after antibiotic treatment.
grown on glass forms protective biofilms, consistent with a role for ...biofilms in persistence. These biofilms consist of towers of bacteria interspersed with individual adherent cells.
A tissue culture model for
biofilms has not been described or evaluated to address whether growth, development and resistance properties are consistent with persistence in the host. Moreover, it is unclear whether the
cells in the biofilm towers and individual bacterial cells have distinct roles in disease.
We evaluated the properties of biofilms of
grown on the immortalized human bronchial epithelial cell line BEAS-2B in relation to persistence in the host. We observed nucleation of biofilm towers and the disposition of individual cells in culture, leading to a model of how tower and individual cells contribute to infection and disease.
With submerged BEAS-2B cells as a substrate, we evaluated growth and development of
biofilms using scanning electron microscopy and confocal laser scanning microscopy. We characterized resistance to erythromycin and complement using minimum inhibitory concentration assays and quantification of colony forming units. We monitored biofilm tower formation using time-lapse microscopic analysis of host-cell-free
cultures.
Bacteria grown on host cells underwent similar development to those grown without host cells, including tower formation, rounding and incidence of individual cells outside towers. Erythromycin and complement significantly reduced growth of
. Towers formed exclusively from pre-existing aggregates of bacteria. We discuss a model of the
biofilm life cycle in which protective towers derive from pre-existing aggregates, and generate individual cytotoxic cells.
can form protective biofilms in a tissue culture model, implicating biofilms in chronic infections, with aggregates of
cells being important for establishing infections.
The poultry-associated bacterium Mycoplasma iowae colonizes multiple sites in embryos, with disease or death resulting. Although M. iowae accumulates in the intestinal tract, it does not cause ...disease at that site, but rather only in tissues that are exposed to atmospheric O₂. The activity of M. iowae catalase, encoded by katE, is capable of rapid removal of damaging H₂O₂from solution, and katE confers a substantial reduction in the amount of H₂O₂produced by Mycoplasma gallisepticum katE transformants in the presence of glycerol. As catalase-producing bacteria are often beneficial to hosts with inflammatory bowel disease, we explored whether M. iowae was exclusively protective against H₂O₂-producing bacteria in a Caenorhabditis elegans model, whether its protectiveness changed in response to O₂levels, and whether expression of genes involved in H₂O₂metabolism and virulence changed in response to O₂levels. We observed that M. iowae was in fact protective against H₂O₂-producing Streptococcus pneumoniae, but not HCN-producing Pseudomonas aeruginosa, and that M. iowae cells grown in 1% O₂promoted survival of C. elegans to a greater extent than M. iowae cells grown in atmospheric O₂. Transcript levels of an M. iowae gene encoding a homolog of Mycoplasma pneumoniae CARDS toxin were 5-fold lower in cells grown in low O₂. These data suggest that reduced O₂, representing the intestinal environment, triggers M. iowae to reduce its virulence capabilities, effecting a change from a pathogenic mode to a potentially beneficial one.
Mycoplasma iowae is a well-established avian pathogen that can infect and damage many sites throughout the body. One potential mediator of cellular damage by mycoplasmas is the production of H2O2 via ...a glycerol catabolic pathway whose genes are widespread amongst many mycoplasma species. Previous sequencing of M. iowae serovar I strain 695 revealed the presence of not only genes for H2O2 production through glycerol catabolism but also the first documented mycoplasma gene for catalase, which degrades H2O2. To test the activity of M. iowae catalase in degrading H2O2, we studied catalase activity and H2O2 accumulation by both M. iowae serovar K strain DK-CPA, whose genome we sequenced, and strains of the H2O2-producing species Mycoplasma gallisepticum engineered to produce M. iowae catalase by transformation with the M. iowae putative catalase gene, katE. H2O2-mediated virulence by M. iowae serovar K and catalase-producing M. gallisepticum transformants were also analyzed using a Caenorhabditis elegans toxicity assay, which has never previously been used in conjunction with mycoplasmas. We found that M. iowae katE encodes an active catalase that, when expressed in M. gallisepticum, reduces both the amount of H2O2 produced and the amount of damage to C. elegans in the presence of glycerol. Therefore, the correlation between the presence of glycerol catabolism genes and the use of H2O2 as a virulence factor by mycoplasmas might not be absolute.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Mycoplasma penetrans is an emerging pathogen with a reduced genome. This bacterium has only previously been cultured from individuals with chronic immunodeficiencies. Here we report the ...characteristics of 4 M. penetrans isolates from the urine of immunocompetent males with nongonococcal urethritis, in comparison with strain HF-2 from an immunocompromised patient. Several features exhibited distinct differences between these isolates and HF-2. Unlike HF-2, all 4 were resistant to azithromycin. They exhibited greater sialic acid-dependent binding to erythrocytes, gliding motility speed, and H2O2 production than HF-2. All new isolates produced thinner capsules than HF-2. Invasiveness varied, with some isolates being more invasive than HF-2 and some less invasive. Cytotoxicity to HeLa cells was similar to HF-2, and all strains could clear extracellular traps produced by innate immune cells. We conclude that subtle differences among M. penetrans strains may be critical for this organism to establish an infection in an otherwise healthy individual.
Four isolates of the bacterium Mycoplasma penetrans from immunocompetent male patients with nongonococcal urethritis exhibited phenotypic differences from a strain isolated from immunocompromised patients, including antibiotic resistance, adherence, invasiveness, motility, capsule thickness, and hydrogen peroxide production.
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