Universal DNA primers amplify bacterial DNA from human fetal membranes and link Fusobacterium nucleatum with prolonged preterm membrane rupture

Cahill, Rachel; Tan, Susern; Dougan, Gordon; Ó’Gaora, Peadar; Pickard, Derek; Kennea, Nigel; Sullivan, Mark; Feldman, Robert G.; Edwards, A. David

doi:10.1093/molehr/gah234

Cited by 50 publications

(45 citation statements)

References 28 publications

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“…The current study differs from previous ones in that bacteria identified in AF were compared with those in the vaginal tract and the oral cavity of the same patient at the DNA level (3,4,10,11,15,16,20). Although other orally related microorganisms, such as F. nucleatum and Capnocytophaga spp., have been isolated from intrauterine infections and have been speculated to originate from the oral cavity, the presence (or absence) of these organisms in the oral cavities of the same patients was not known (4,10,11,16,20).…”

Section: Discussionmentioning

confidence: 79%

“…Although other orally related microorganisms, such as F. nucleatum and Capnocytophaga spp., have been isolated from intrauterine infections and have been speculated to originate from the oral cavity, the presence (or absence) of these organisms in the oral cavities of the same patients was not known (4,10,11,16,20). Oral Bergeyella could be yet another opportunistic pathogen whose association with periodontal disease is not known but which is pathogenic when transmitted to other parts of the body such as the pregnant uterus.…”

Section: Discussionmentioning

confidence: 99%

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Transmission of an Uncultivated Bergeyella Strain from the Oral Cavity to Amniotic Fluid in a Case of Preterm Birth

Han¹,

Ikegami²,

Bissada³

et al. 2006

J Clin Microbiol

134

136

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Intrauterine infection is a recognized cause of preterm birth. The infectious organisms are believed to originate primarily from the vaginal tract and secondarily from other parts of the body. It is plausible that microbes in the oral cavity can be transmitted to the pregnant uterus. However, direct evidence supporting such a transmission is lacking. In this study, amniotic fluids of 34 pregnant women were examined by PCR using 16S and 23S rRNA universally conserved primers. Bacterial DNA was amplified from the only patient with clinical intrauterine infection and histologic necrotizing acute and chronic chorioamnionitis. One strain, Bergeyella sp. clone AF14, was detected and was 99.7% identical to a previously reported uncultivated oral Bergeyella strain, clone AK152, at the 16S rRNA level. The same strain was detected in the subgingival plaque of the patient but not in her vaginal tract. The 16S-23S rRNA sequence of clone AF14 matched exactly with the sequences amplified from the patient's subgingival plaque. These observations suggest that the Bergeyella strain identified in the patient's intrauterine infection originated from the oral cavity. This is the first direct evidence of oral-utero microbial transmission. The patient's periodontal health during pregnancy was unclear. She did not have detectable periodontal disease during postpartum examination. Bergeyella spp. had not been previously associated with preterm birth and were detected in subgingival plaque of women without clinical levels of intrauterine infection. Uncultivated species may be overlooked opportunistic pathogens in preterm birth. This study sheds new light on the implication of oral bacteria in preterm birth.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Transmission of an Uncultivated Bergeyella Strain from the Oral Cavity to Amniotic Fluid in a Case of Preterm Birth

Han¹,

Ikegami²,

Bissada³

et al. 2006

J Clin Microbiol

134

136

View full text Add to dashboard Cite

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“…It is a Gram-negative anaerobic oral species and an opportunistic human pathogen associated with various forms of periodontal disease. The organism can be isolated at a frequency of 10 -30% from AF of women in preterm labor with intact membranes (3,4,9,11) and detected in 83% of PTB with premature rupture of membranes by PCR (11). A causal relationship between F. nucleatum and adverse pregnancy outcome has been established in our previous studies in mice.…”

mentioning

confidence: 87%

Fusobacterium nucleatumInduces Fetal Death in Mice via Stimulation of TLR4-Mediated Placental Inflammatory Response

Liu¹,

Redline

Han

2007

The Journal of Immunology

148

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Intrauterine infection plays a pivotal role in preterm birth (PTB) and is characterized by inflammation. Currently, there is no effective therapy available to treat or prevent bacterial-induced PTB. Using Fusobacterium nucleatum, a Gram-negative anaerobe frequently associated with PTB, as a model organism, the mechanism of intrauterine infection was investigated. Previously, it was shown that F. nucleatum induced preterm and term stillbirth in mice. Fusobacterial-induced placental infection was characterized by localized bacterial colonization, inflammation, and necrosis. In this study, F. nucleatum was shown to activate both TLR2 and TLR4 in vitro. In vivo, the fetal death rate was significantly reduced in TLR4-deficient mice (C57BL/6 TLR4−/− and C3H/HeJ (TLR4d/d)), but not in TLR2-deficient mice (C57BL/6 TLR2−/−), following F. nucleatum infection. The reduced fetal death in TLR4-deficient mice was accompanied by decreased placental necroinflammatory responses in both C57BL/6 TLR4−/− and C3H/HeJ. Decreased bacterial colonization in the placenta was observed in C3H/HeJ, but not in C57BL/6 TLR4−/−. These results suggest that inflammation, rather than the bacteria per se, was the likely cause of fetal loss. TLR2 did not appear to be critically involved, as no difference in bacterial colonization, inflammation, or necrosis was observed between C57BL/6 and C57BL/6 TLR2−/− mice. A synthetic TLR4 antagonist, TLR4A, significantly reduced fusobacterial-induced fetal death and decidual necrosis without affecting the bacterial colonization in the placentas. TLR4A had no bactericidal activity nor did it affect the birth outcome in sham-infected mice. TLR4A could have promise as an anti-inflammatory agent for the treatment or prevention of bacterial-induced preterm birth.

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“…Periodontal disease is a risk factor for preterm labor (41)(42)(43)(44)(45), and F. nucleatum has been associated with preterm birth (46)(47)(48)(49)(50), stillbirth (51), and early-onset neonatal sepsis (52).…”

mentioning

confidence: 99%

Fap2 of Fusobacterium nucleatum Is a Galactose-Inhibitable Adhesin Involved in Coaggregation, Cell Adhesion, and Preterm Birth

et al. 2015

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Fusobacterium nucleatum is a common oral anaerobe involved in periodontitis that is known to translocate and cause intrauterine infections. In the oral environment, F. nucleatum adheres to a large diversity of species, facilitating their colonization and creating biological bridges that stabilize the multispecies dental biofilm. Many of these interactions (called coadherences or coaggregations) are galactose sensitive. Galactose-sensitive interactions are also involved in the binding of F. nucleatum to host cells. Hemagglutination of some F. nucleatum strains is also galactose sensitive, suggesting that a single galactose-sensitive adhesin might mediate the interaction of fusobacteria with many partners and targets. In order to identify the fusobacterial galactose-sensitive adhesin, a system for transposon mutagenesis in fusobacteria was created. The mutant library was screened for hemagglutination deficiency, and three clones were isolated. All three clones were found to harbor the transposon in the gene coding for the Fap2 outer membrane autotransporter. The three fap2 mutants failed to show galactose-inhibitable coaggregation with Porphyromonas gingivalis and were defective in cell binding. A fap2 mutant also showed a 2-log reduction in murine placental colonization compared to that of the wild type. Our results suggest that Fap2 is a galactose-sensitive hemagglutinin and adhesin that is likely to play a role in the virulence of fusobacteria.

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Universal DNA primers amplify bacterial DNA from human fetal membranes and link Fusobacterium nucleatum with prolonged preterm membrane rupture

Cited by 50 publications

References 28 publications

Transmission of an Uncultivated Bergeyella Strain from the Oral Cavity to Amniotic Fluid in a Case of Preterm Birth

Transmission of an Uncultivated Bergeyella Strain from the Oral Cavity to Amniotic Fluid in a Case of Preterm Birth

Fusobacterium nucleatumInduces Fetal Death in Mice via Stimulation of TLR4-Mediated Placental Inflammatory Response

Fap2 of Fusobacterium nucleatum Is a Galactose-Inhibitable Adhesin Involved in Coaggregation, Cell Adhesion, and Preterm Birth

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