Regular articleUreaplasma and BPD
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Microbiology of Ureaplasma species
Ureaplasma spp. are among the smallest free-living, self-replicating microorganisms. They have an extremely low G+C content of 25.5% (or the highest A+T composition) within open reading frames of any prokaryotes sequenced to date. Ureaplasma spp. have evolved from Gram-positive bacteria by degenerative evolution to lose the peptidoglycan cell wall.4 As their name suggests, Ureaplasma spp. utilize urea as their sole source of carbon, producing ammonia as a metabolic product.5 Currently, there
Virulence of Ureaplasma species
Several proteins have been proposed as virulence factors. The mba gene encodes for MBA, the major surface-exposed lipoprotein. MBA is thought to be the major virulence factor of Ureaplasma spp. and is the predominant antigen recognized by the host immune system during infection.4 Ureaplasma spp. can alter the expression of their MBA in order to evade host immune responses and maintain chronicity of infection.8., 9., 10. Ureaplasma phospholipase A and C activities were identified by in vitro
Ureaplasma spp. perinatal pathogens causing preterm birth
The microbial invasion of amniotic cavity associated with preterm birth is relatively unique among infectious diseases in humans. The microbes are mostly opportunistic commensal vaginal organisms of low pathogenicity in otherwise healthy women. Polymicrobial growth is common from amniotic fluid from chorioamnionitis, and Ureaplasma spp. are the organisms most frequently isolated, although they rarely cause infections elsewhere.13., 17. The strongest evidence that Ureaplasma can cause preterm
Host response to Ureaplasma infection
Microbial recognition by innate immune systems can be mediated by a variety of germline-encoded receptors, including Toll-like receptors (TLRs), RIG-like receptors (RLRs), Nod-like receptors (NLRs), and cytosolic DNA sensors such as the HIN-200 family member AIM2.24 Ureaplasma spp. lack a gram-negative or gram-positive bacterial cell wall, thus are devoid of lipopolysaccharides or peptidoglycans—the microbial products that are potent activators of TR4 (lipopolysaccharide or LPS) and the TLR2 or
Ureaplasma and immune modulation
Chronic infections can induce a state of immune paralysis called endotoxin tolerance. Thus leukocytes from patients with sepsis or recovering from typhoid fever can have endotoxin tolerance.32., 33. We reported that in sheep repeated intra-amniotic injections of lipopolysaccharide (LPS endotoxin), a constituent of cell wall of gram-negative bacteria, induces tolerance to a variety of toll-like receptor agonists in the preterm fetus.34., 35., 36. Interestingly, chronic intra-amniotic
Ureaplasma species and inflammation in the developing lung—animal studies
Ureaplasma infection of the developing lung has been studied primarily in sheep and non-human primates. Intra-amniotic injection of Ureaplasma in early gestation sheep resulted in efficient colonization and a 5-log increase in the Ureaplasma in amniotic fluid counts that persisted for 3 months to term with very little overt adverse effects in the ewe, consistent with a commensal-like host response.15 Interestingly, after a chronic exposure to intra-amniotic Ureaplasma, all of the fetal lungs
Ureaplasma species and lung inflammation in the developing lung—Human studies
The lung pathology of archived autopsy specimens from Ureaplasma infected preterm infants demonstrated increased lung fibrosis, elastic fiber accumulation, smooth muscle actin, and increased tumor necrosis factor alpha (TNFα) and transforming growth factor beta 1 (TGFβ1) immunoreactivity.45., 46. Elevated maternal and fetal or newborn antibody titers to Ureaplasma correlated with an increased incidence of stillbirth and infants with fatal neonatal respiratory disease.29 The findings from these
Pathogenesis of BPD
The most predictive risk factors for development of BPD are gestational age, birth weight, duration of respiratory support, fraction of inspired oxygen (FiO2), race and gender.47 Although these risk factors hold true on a population basis, individual infants who develop BPD have different trajectories toward developing BPD. For instance, if the need for supplemental oxygen is used as a proxy for lung injury, then 3 patterns (or subsets) of BPD are discernible.48., 49. In a study of preterm
Clinical and epidemiological studies of Ureaplasma and BPD
Ureaplasma spp. are the organisms most frequently associated with chorioamnionitis and very preterm delivery.53 However, the contribution of Ureaplasma or chorioamnionitis to BPD is less clear. Several single center studies reported the association of Ureaplasma in the respiratory secretions of newborns with the development of BPD.54., 55., 56., 57., 58. Some studies used the BPD definition of oxygen supplementation at 28 days, while others used the more current definition of BPD as the need
Treatment with antimicrobial agents
Since Ureaplasma is the most common organism isolated in women with chorioamnionitis it is instructive to review antibiotic trials for chorioamnionitis. Antenatal trials of antimicrobial use in the setting of preterm labor have yielded mixed results. Mercer et al.75 randomized 614 women with preterm premature rupture of membranes between 24 and 32 weeks to ampicillin plus erythromycin or placebo for a 7 day treatment course.75 The women randomized to antibiotics had a higher latency and the
Summary and conclusions
Ureaplasma species are the organisms most associated with chorioamnionitis and preterm delivery. Although there is controversy regarding the role of Ureaplasma in BPD, experimental evidence and clinical/epidemiological data demonstrate that Ureaplasma species can increase the risk for BPD in preterm infants. Antenatal exposure to Ureaplasma increases surfactant production, increases lung volumes and induces pulmonary inflammation with disordered alveolar development in preterm sheep.
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2021, Biochimica et Biophysica Acta - Molecular Basis of DiseaseCitation Excerpt :It plays an important role in perinatal and postnatal morbidities increasing bronchopulmonary dysplasia, neonatal sepsis and meningitis [346]. Though reports in the pathogenesis of bronchopulmonary dysplasia in the offspring were initially controversial, most of the evidence is consistent with a role of UU in the pathogenesis of this disease [350–352]. This can lead to prolonged mechanical ventilation and certain chronic lung diseases in neonates with premature birth [353–355].
Prematurity and Intrauterine Insults
2021, Encyclopedia of Respiratory Medicine, Second EditionDifferent degrees of maternal Ureaplasma colonization and its correlation with bronchopulmonary dysplasia in <32 weeks' preterm infants
2019, Pediatrics and NeonatologyCitation Excerpt :With respect to maternal factors, recent studies have indicated a strong relationship between maternal Ureaplasma colonization and pregnancy outcomes.22,23 Kallapur et al.24 found that an ascending infection through the cervix to the choriodecidual space led to generalized inflammation and produced proinflammatory mediators that initiated preterm labor. The mechanism by which Ureaplasma colonization of the lower genital tract causes intrauterine infection and finally leads to adverse pregnancy outcomes remains unclear.
Molecular detection of bacteria, placental inflammation, and neonatal sepsis risk
2024, Journal of PerinatologySuperoxide dismutase for bronchopulmonary dysplasia in preterm infants
2023, Cochrane Database of Systematic Reviews
Funded by NIH grant HD57869 (to SGK).