Interaction of the putative tyrosine recombinases RipX (UU145), XerC (UU222), and CodV (UU529) of<i>Ureaplasma parvum</i>serovar 3 with specific DNA

Zimmerman, Carl-Ulrich R.; Rosengarten, Renate; Spergser, Joachim

doi:10.1111/1574-6968.12077

Cited by 9 publications

(6 citation statements)

References 31 publications

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“…urealyticum were nonetheless reported to cause male urethritis and endometritis in pregnancy more frequently than U . parvum , and relevant genetic differences among serovars were described [69, 70]. Compared to U .…”

Section: Discussionmentioning

confidence: 99%

Differential modulation of pulmonary caspases: Is this the key to Ureaplasma-driven chronic inflammation?

Silwedel¹,

Fehrholz²,

Speer³

et al. 2019

PLoS ONE

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Although accepted agents in chorioamnionitis and preterm birth, the role of Ureaplasma species (spp.) in inflammation-driven morbidities of prematurity, including the development of bronchopulmonary dysplasia, remains controversial. To add to scarce in vitro data addressing the pro-inflammatory capacity of Ureaplasma spp., pulmonary epithelial-like A549 cells and human pulmonary microvascular endothelial cells (HPMEC) were incubated with Ureaplasma (U . ) urealyticum , U . parvum , and Escherichia coli lipopolysaccharide (LPS). Ureaplasma isolates down-regulated caspase mRNA levels in A549 cells (caspase 8: p <0.001, 9: p <0.001, vs. broth), while increasing caspase protein expression, enzyme activity, and cell death in HPMEC (active caspase 3: p <0.05, caspase 8: p <0.05, active caspase 9: p <0.05, viability: p <0.05). LPS, contrarily, induced caspase mRNA expression in HPMEC (caspase 3: p <0.01, 4: p <0.001, 5: p <0.001, 8: p <0.001, vs. control), but not in A549 cells, and did not affect enzyme activity or protein levels in either cell line. LPS, but neither Ureaplasma isolate, enhanced mRNA expression of pro-inflammatory interleukin ( IL)-6 in both A549 ( p <0.05, vs. control) and HPMEC ( p <0.001) as well as tumor necrosis factor-α ( p <0.01), IL-1β ( p <0.001), and IL-8 ( p <0.05) in HPMEC. We are therefore the first to demonstrate a differential modulation of pulmonary caspases by Ureaplasma spp. in vitro . Ureaplasma -driven enhanced protein expression and activity of caspases in pulmonary endothelial cells result in cell death and may cause structural damage. Down-regulated caspase mRNA in pulmonary epithelial cells, contrarily, may indicate Ureaplasma -induced inhibition of apoptosis and prevent effective immune responses. Both may ultimately contribute to chronic Ureaplasma colonization and long-term pulmonary inflammation.

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Section: Discussionmentioning

confidence: 99%

Differential modulation of pulmonary caspases: Is this the key to Ureaplasma-driven chronic inflammation?

Silwedel¹,

Fehrholz²,

Speer³

et al. 2019

PLoS ONE

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“…Zimmerman and colleagues further investigated the role of DNA inversion sites within the Ureaplasma genome and demonstrated experimentally that the mba paralogues UU171 and UU172 and the orthologue UU144 were also involved in site-specific DNA inversion/recombination (256). Furthermore, it was shown that the XerC tyrosine recombinase gene of U. parvum is the most likely mediator of these DNA inversion events (257). Subsequent experimental investigation into the ability of XerC to process the recombination event proved successful, indicating that this tyrosine recombinase is able to induce DNA inversion events (258), representing the first evidence of a mechanism which may govern antigenic phase variation in Ureaplasma spp.…”

Section: Multiple-banded Antigen (Mba)mentioning

confidence: 99%

The Human Ureaplasma Species as Causative Agents of Chorioamnionitis

et al. 2017

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SUMMARY The human Ureaplasma species are the most frequently isolated microorganisms from the amniotic fluid and placentae of women who deliver preterm and are also associated with spontaneous abortions or miscarriages, neonatal respiratory diseases, and chorioamnionitis. Despite the fact that these microorganisms have been habitually found within placentae of pregnancies with chorioamnionitis, the role of Ureaplasma species as a causative agent has not been satisfactorily explained. There is also controversy surrounding their role in disease, particularly as not all women infected with Ureaplasma spp. develop chorioamnionitis. In this review, we provide evidence that Ureaplasma spp. are associated with diseases of pregnancy and discuss recent findings which demonstrate that Ureaplasma spp. are associated with chorioamnionitis, regardless of gestational age at the time of delivery. Here, we also discuss the proposed major virulence factors of Ureaplasma spp., with a focus on the multiple-banded antigen (MBA), which may facilitate modulation/alteration of the host immune response and potentially explain why only subpopulations of infected women experience adverse pregnancy outcomes. The information presented within this review confirms that Ureaplasma spp. are not simply “innocent bystanders” in disease and highlights that these microorganisms are an often underestimated pathogen of pregnancy.

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“…Zimmerman et al ( 2009 , 2013 ) in in vitro experiments demonstrated inversion events that occurred between the mba and other regions with the genome of U. parvum serovars 3. These events were confirmed on both the genomic and protein level.…”

Section: Discussionmentioning

confidence: 99%

Ureaplasma Species Multiple Banded Antigen (MBA) Variation Is Associated with the Severity of Inflammation In vivo and In vitro in Human Placentae

Sweeney

Kallapur

Meawad

et al. 2017

Front. Cell. Infect. Microbiol.

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Background: The multiple banded antigen (MBA), a surface-exposed lipoprotein, is a proposed virulence factor of Ureaplasma spp. We previously demonstrated that the number of Ureaplasma parvum MBA size variants in amniotic fluid was inversely proportional to the severity of chorioamnionitis in experimentally infected pregnant sheep. However, the effect of ureaplasma MBA size variation on inflammation in human pregnancies has not been reported.Methods: Ureaplasmas isolated from the chorioamnion of pregnant women from a previous study (n = 42) were speciated/serotyped and MBA size variation was demonstrated by PCR and western blot. Results were correlated with the severity of chorioamnionitis and cord blood cytokines. In vitro, THP-1-derived macrophages were exposed to recombinant-MBA proteins of differing sizes and NF-κB activation and cytokine responses were determined.Results: MBA size variation was identified in 21/32 (65.6%) clinical isolates (in 10 clinical isolates MBA size variation was unable to be determined). Any size variation (increase/decrease) of the MBA (regardless of Ureaplasma species or serovar) was associated with mild or absent chorioamnionitis (P = 0.023) and lower concentrations of cord blood cytokines IL-8 (P = 0.04) and G-CSF (P = 0.008). In vitro, recombinant-MBA variants elicited different cytokine responses and altered expression of NF-κB p65.Conclusion: This study demonstrates that size variation of the ureaplasma MBA protein modulates the host immune response in vivo and in vitro.

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Interaction of the putative tyrosine recombinases RipX (UU145), XerC (UU222), and CodV (UU529) ofUreaplasma parvumserovar 3 with specific DNA

Cited by 9 publications

References 31 publications

Differential modulation of pulmonary caspases: Is this the key to Ureaplasma-driven chronic inflammation?

Differential modulation of pulmonary caspases: Is this the key to Ureaplasma-driven chronic inflammation?

The Human Ureaplasma Species as Causative Agents of Chorioamnionitis

Ureaplasma Species Multiple Banded Antigen (MBA) Variation Is Associated with the Severity of Inflammation In vivo and In vitro in Human Placentae

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