A Metabolic Enzyme as a Primary Virulence Factor of<i>Mycoplasma mycoides</i>subsp.<i>mycoides</i>Small Colony

Pilo, Paola; Vilei, Edy M.; Peterhans, Ernst; Bonvin-Klotz, Laetitia; Stoffel, Michael; Dobbelaere, Dirk; Frey, Joachim

doi:10.1128/jb.187.19.6824-6831.2005

Cited by 140 publications

(224 citation statements)

References 45 publications

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“…This strain may represent the closest relative to the ancestral strains that circulated in Europe in the 19th century. More recent European strains differ from PO1967 notably by a deletion of 8.8 kbp, which includes genes encoding a glycerol transporter that may be associated with MmmSC virulence [30,44]. Unfortunately MmmSC strains circulating prior to 1967 in Europe are not available.…”

Section: Epidemiological Analysismentioning

confidence: 99%

Genotyping ofMycoplasma mycoidessubsp.mycoidesSC by multilocus sequence analysis allows molecular epidemiology of contagious bovine pleuropneumonia

et al. 2008

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-Mycoplasma mycoides subsp. mycoides SC (MmmSC) is the etiological agent of contagious bovine pleuropneumonia (CBPP). Although eradicated in most developed countries, the disease reappeared in Europe in the 1990s. This reappearance may have been caused either by importation from sub-Saharan Africa, where CBPP is still endemic, or by the reemergence of virulent strains in Europe, as suggested by earlier studies. A multilocus sequence analysis scheme has been developed to address this issue and, most importantly, to be able to monitor new epidemics. The alignment of the full genome sequence of the reference strain PG1 and the partial genome sequence of a pathogenic strain allowed the identification of polymorphic sites. Nineteen initial loci were selected within housekeeping genes, genes of unknown function and non coding sequences. The suitability of these loci for genotyping MmmSC strains was first tested on six strains of diverse geographic origin. The analyses showed that the published PG1 sequence contained a number of specific polymorphisms that were therefore of no use for molecular typing. Among the eight informative polymorphic loci finally selected, only one (ftsY) was positioned within a housekeeping gene. Three main groups and 31 different allelic profiles were identified among 51 strains and strain variants examined. Cluster analysis confirmed that European strains from the 1990s did not originate from Africa. It also showed a genetic link between a European strain isolated in 1967 and those found in southern Africa and Australia. This was in agreement with historical data showing that CBPP was introduced in these regions during colonisation in the 19th century.Mycoplasma mycoides / contagious bovine pleuropneumonia / multilocus sequence analysis / molecular epidemiology

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Section: Epidemiological Analysismentioning

confidence: 99%

Genotyping ofMycoplasma mycoidessubsp.mycoidesSC by multilocus sequence analysis allows molecular epidemiology of contagious bovine pleuropneumonia

et al. 2008

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“…Cytotoxicity assays were performed essentially as described for M. mycoides subsp. mycoides SC (31). The various pneumococcal strains (with or without the indicated treatments) were used to infect confluent HBMEC monolayers in 8-well chamber tissue culture slides (Thermo Scientific) at a multiplicity of infection of 100 bacteria per cell, for 2 hours.…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, an ortholog of pneumococcal GlpO from Mycoplasma mycoides subsp. mycoides Small Colony has been reported to be cytotoxic for embryonic calf nasal epithelial cells (31,32). We thus hypothesized that GlpO could contribute to pathogenesis of meningitis by release of H 2 O 2 from metabolism of α-glycerophosphate present in the brain.…”

Section: Glpo Is Cytotoxic Towardmentioning

confidence: 99%

Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice

et al. 2012

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Streptococcus pneumoniae is the most common cause of severe bacterial meningitis in children, the elderly, and immunocompromised individuals. To identify virulence factors preferentially expressed during meningitis, we conducted niche-specific genome-wide in vivo transcriptomic analysis after intranasal infection of mice with serotype 4 or 6A pneumococci. The expression of 34 bacterial genes was substantially altered in brain tissue of mice infected with either of the 2 strains. Ten upregulated genes were common to both strains, 7 of which were evaluated for their role in the development of meningitis. One previously uncharacterized protein, α-glycerophosphate oxidase (GlpO), was cytotoxic for human brain microvascular endothelial cells (HBMECs) via generation of H 2 O 2 . A glpO deletion mutant was defective in adherence to HBMECs in vitro as well as in progression from the blood to the brain in vivo. Mutant bacteria also induced markedly reduced meningeal inflammation and brain pathology compared with wild type, despite similar levels of bacteremia. Immunization of mice with GlpO protected against invasive pneumococcal disease and provided additive protection when formulated with pneumolysin toxoid. Our results provide the basis of a strategy that can be adapted to identify genes that contribute to the development of meningitis caused by other pathogens.

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“…Blocking GlpO by monospecific anti-GlpO antibodies blocked the release of H 2 O 2 and concomitantly inhibited the cytotoxicity of M. mycoides subsp. mycoides SC to ECaNEp cells (14). The H 2 O 2 -mediated cytotoxic effect on host cells was found to be triggered by the close contact between mycoplasmas and ECaNEp cells allowing H 2 O 2 to be translocated to the cytosol of the host cells, while exogenous H 2 O 2 in axenic medium was not sufficient to cause cytotoxicity (14).…”

mentioning

confidence: 99%

“…mycoides SC was identified as a membrane protein that plays a central role in the cytotoxicity of M. mycoides subsp. mycoides SC to embryonic calf nasal epithelial (ECaNEp) cells (14). GlpO catalyzes the oxidation of glycerol-3-phosphate, followed by the release of H 2 O 2 (18).…”

mentioning

confidence: 99%

Cytotoxicity ofMycoplasma mycoidessubsp.mycoidesSmall Colony Type to Bovine Epithelial Cells

et al. 2008

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The cytotoxicities of various strains of Mycoplasma mycoides subsp. mycoides small colony type (SC), the agent of contagious bovine pleuropneumonia (CBPP), were measured in vitro using embryonic calf nasal epithelial (ECaNEp) cells. Strains isolated from acute cases of CBPP induced high cytotoxicity in the presence of glycerol, concomitant with the release of large amounts of toxic H 2 O 2 that were found to be translocated into the cytoplasms of the host cells by close contact of the Mycoplasma strains with the host cells. Currently used vaccine strains also showed high cytotoxicity and high H 2 O 2 release, indicating that they are attenuated in another virulence attribute. Strains isolated from recent European outbreaks of CBPP with mild clinical signs, which are characterized by a defect in the glycerol uptake system, released small amounts of H 2 O 2 and showed low cytotoxicity to ECaNEp cells. M. mycoides subsp. mycoides SC strain PG1 released large amounts of H 2 O 2 but was only slightly cytotoxic. PG1 was found to have a reduced capacity to bind to ECaNEp cells and was unable to translocate H 2 O 2 into the bovine cells, in contrast to virulent strains that release large amounts of H 2 O 2 . Thus, an efficient translocation of H 2 O 2 into host cells is a prerequisite for the cytotoxic effect and requires an intact adhesion mechanism to ensure a close contact between mycoplasmas and host cells.

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A Metabolic Enzyme as a Primary Virulence Factor ofMycoplasma mycoidessubsp.mycoidesSmall Colony

Cited by 140 publications

References 45 publications

Genotyping ofMycoplasma mycoidessubsp.mycoidesSC by multilocus sequence analysis allows molecular epidemiology of contagious bovine pleuropneumonia

Genotyping ofMycoplasma mycoidessubsp.mycoidesSC by multilocus sequence analysis allows molecular epidemiology of contagious bovine pleuropneumonia

Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice

Cytotoxicity ofMycoplasma mycoidessubsp.mycoidesSmall Colony Type to Bovine Epithelial Cells

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