Mycoplasma pneumoniae: a reduced-genome intracellular bacterial pathogen

Meseguer, María Antonia; Álvarez, Alberto; Rejas, María Teresa; Sánchez, Carlos J.; Pérez-Díaz, J C; Baquero, Fernando

doi:10.1016/s1567-1348(02)00151-x

Cited by 60 publications

(42 citation statements)

References 39 publications

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“…In animal models of M. pneumoniae pneumonia, treatment with quinolones, ketolides, clarithromycin, and azithromycin has failed to eradicate this organism from the respiratory tract In agreement with these reports, the present study demonstrated that although LBM415 therapy reduced the levels of the organism in quantitative M. pneumoniae cultures, it did not result in elimination of the organism. The ability of M. pneumoniae to reside and replicate in human cells has recently been described (9,31). The possibility that M. pneumoniae might move transiently into an intracellular reservoir could explain the common finding of the prolonged recovery of this organism from respiratory tract secretions even after clinically successful therapy.…”

Section: Discussionsupporting

confidence: 79%

Evaluation of LBM415 (NVP PDF-713), a Novel Peptide Deformylase Inhibitor, for Treatment of Experimental Mycoplasma pneumoniae Pneumonia

Fonseca-Aten¹,

Salvatore²,

Mejías³

et al. 2005

Antimicrob Agents Chemother

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Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. We evaluated the efficacy of LBM415, a novel peptide deformylase inhibitor antimicrobial agent, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were intranasally inoculated once with 10 7 CFU of M. pneumoniae. Groups of mice were treated with LBM415 (50 mg/kg of body weight) or placebo subcutaneously daily for 13 days, starting 24 h after inoculation. Groups of mice were evaluated at the baseline; at days of treatment 1, 3, 6, and 13; and at 7 days after treatment. The MIC of LBM415 against M. pneumoniae was <0.005 g/ml. LBM415-treated mice had significantly lower bronchoalveolar lavage fluid M. pneumoniae concentrations than placebo-treated mice on days 6 and 13 of treatment. Compared with placebo treatment, therapy with LBM415 significantly decreased lung histopathology scores at days 3, 6, and 13 of treatment and at 7 days after treatment. Airway obstruction was significantly lower in LBM415-treated mice than in placebotreated mice on days 1, 3, and 6 of treatment and after 7 days of therapy, while airway hyperresponsiveness was significantly lower only on day 3 of therapy. The bronchoalveolar lavage fluid concentrations of tumor necrosis factor alpha, gamma interferon (IFN-␥), interleukin-6 (IL-6), IL-12, KC (functional IL-8), monocyte chemotactic protein 1, macrophage inflammatory protein 1␣, monokine induced by IFN-␥, and IFN-inducible protein 10 were significantly reduced in LBM415-treated mice compared with the levels in placebo-treated mice. There were no differences in the bronchoalveolar lavage fluid concentrations of granulocyte-macrophage colonystimulating factor, IL-1␤, IL-2, IL-4, IL-5, and IL-10 between the two groups of mice. LBM415 therapy had beneficial microbiologic, histologic, respiratory, and immunologic effects on acute murine M. pneumoniae pneumonia.Mycoplasma pneumoniae is an important cause of upper and lower respiratory tract infections in children and adults and is responsible for as many as 40% of cases of community-acquired pneumonia (7,15,28,33). Tetracyclines, macrolides, ketolides, and fluoroquinolones have in vitro activities against M. pneumoniae (43, 44). Most of these agents are primarily bacteriostatic for M. pneumoniae, and only the fluoroquinolones have been shown to be bactericidal (10, 42). While M. pneumoniae can be cultured from respiratory secretions for long periods after acute infection even after appropriate antimicrobial therapy, most antibiotics produce satisfactory clinical results, with a significant reduction in the duration of symptoms compared with no treatment (30,36). Macrolide and related antibiotics are generally considered the therapy of choice for M. pneumoniae infections in children and adults. Strains with acquired resistance to macrolides have rarely been described (29).LBM415 (previously known as NVP PDF-713) is a novel inhibitor of the bacterial enzyme peptide deformylase (PDF) and has been documented to have in vitro activity against...

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Section: Discussionsupporting

confidence: 79%

Evaluation of LBM415 (NVP PDF-713), a Novel Peptide Deformylase Inhibitor, for Treatment of Experimental Mycoplasma pneumoniae Pneumonia

Fonseca-Aten¹,

Salvatore²,

Mejías³

et al. 2005

Antimicrob Agents Chemother

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“…In addition, the highly invasive Mycoplasma penetrans (Mpen) was observed to attain cytoplasmic and perinuclear localization in WI-38 cells (Baseman et al, 1995). Furthermore, Mycoplasma pneumoniae (Mp), which is the closest relative to Mg, achieves cytoplasmic and perinuclear localization in WI-38 (Baseman et al, 1995) by 2 h, and a similar localization was reported for this pathogen within the human hepatocyte cell line Hep-G2 (Meseguer et al, 2003). Yavlovich et al (2004) observed Mp internalization in human lung carcinoma A549 cells but not in HeLa epithelial cells.…”

Section: Discussionmentioning

confidence: 75%

Interaction of Mycoplasma genitalium with host cells: evidence for nuclear localization

et al. 2008

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Mycoplasma genitalium (Mg) is a mollicute that causes a range of human urogenital infections. A hallmark of these bacteria is their ability to establish chronic infections that can persist despite completion of appropriate antibiotic therapies and intact and functional immune systems. Intimate adherence and surface colonization of mycoplasmas to host cells are important pathogenic features. However, their facultative intracellular nature is poorly understood, partly due to difficulties in developing and standardizing cellular interaction model systems. Here, we characterize growth and invasion properties of two Mg strains (G37 and 1019V). Mg G37 is a high-passage laboratory strain, while Mg 1019V is a low-passage isolate recovered from the cervix. The two strains diverge partially in gene sequences for adherence-related proteins and exhibit subtle variations in their axenic growth. However, with both strains and consistent with our previous studies, a subset of adherent Mg organisms invade host cells and exhibit perinuclear targeting. Remarkably, intranuclear localization of Mg proteins is observed, which occurred as early as 30 min after infection. Mg strains deficient in adherence were markedly reduced in their ability to invade and associate with perinuclear and nuclear sites.

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“…M. pneumoniae is primarily an extracellular pathogen that causes respiratory illness through its close adherence to respiratory epithelial cells, mediated by a highly specialized attachment organelle that contains a network of adhesion proteins including the P1 and P30 adhesins [27, 28•, 29•]. Recent in vitro studies have demonstrated that internalization and intracellular survival of M. pneumoniae can occur [27,30,31]. The ability to invade and survive within epithelial cells is of paramount importance because it could provide a mechanism for immune evasion, protection from the action of certain antibiotics, and initiation of the process of dissemination from mucosal sites [27].…”

Section: Microbiologymentioning

confidence: 99%

Mycoplasma pneumoniae: Innocent Bystander or a True Cause of Central Nervous System Disease?

Bitnun

Richardson

2010

Curr Infect Dis Rep

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The consistency with which Mycoplasma pneumoniae has been implicated as a cause of encephalitis, and the increased incidence of central nervous system (CNS) disease observed during M. pneumoniae respiratory outbreaks, support the role of M. pneumoniae as a CNS pathogen. Three pathophysiologic mechanisms have been proposed: direct infection, autoimmunity, and vascular occlusion. Recent evidence demonstrating the organism's ability to survive intracellularly, presence of its DNA in the serum of individuals with acute encephalitis, case reports in which the organism is detected in brain parenchyma or cerebrospinal fluid (CSF), and animal data demonstrating CNS invasion by several Mycoplasma species support the contention that M. pneumoniae is capable of direct infection of the CNS. Because of limitations of current serologic assays and difficulty in interpreting the significance of positive polymerase chain reaction results in regard to acuity of infection and viability of the organism, the diagnosis of M. pneumoniae-associated CNS disease should be based on a combination of positive tests and exclusion of alternative diagnoses.

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Mycoplasma pneumoniae: a reduced-genome intracellular bacterial pathogen

Cited by 60 publications

References 39 publications

Evaluation of LBM415 (NVP PDF-713), a Novel Peptide Deformylase Inhibitor, for Treatment of Experimental Mycoplasma pneumoniae Pneumonia

Evaluation of LBM415 (NVP PDF-713), a Novel Peptide Deformylase Inhibitor, for Treatment of Experimental Mycoplasma pneumoniae Pneumonia

Interaction of Mycoplasma genitalium with host cells: evidence for nuclear localization

Mycoplasma pneumoniae: Innocent Bystander or a True Cause of Central Nervous System Disease?

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