Role of Ureaplasma Respiratory Tract Colonization in Bronchopulmonary Dysplasia Pathogenesis: Current Concepts and Update

Abstract

Respiratory tract colonization with the genital mycoplasma species Ureaplasma parvum and Ureaplasma urealyticum in preterm infants is a significant risk factor for bronchopulmonary dysplasia (BPD). Recent studies of the ureaplasmal genome, animal infection models, and human infants have provided a better understanding of specific virulence factors, pathogen-host interactions, and variability in genetic susceptibility that contribute to chronic infection, inflammation, and altered lung development. This review provides an update on the current evidence supporting a causal role of ureaplasma infection in BPD pathogenesis. The current status of antibiotic trials to prevent BPD in Ureaplasma-infected preterm infants is also reviewed.

Keywords: Bronchopulmonary dysplasia; Macrolide antibiotics; Prematurity; Ureaplasma parvum; Ureaplasma urealyticum.

Figure 1. Persistent colonization of Ureaplasma in the sheep amniotic compartment

Pregnant ewes (n=20) were given intraamniotic injection of Ureaplasma Parvum (UP) (2 × 10⁴ CFU) at 55d gestational age (term=150d). Amniocentesis was done at regular intervals until term gestation and the amniotic fluid titers of Ureaplasma were determined. There was a rapid growth of UP and the titers persisted till term gestation demonstrating poor clearance of UP. Data from Dando SJ, Nitsos I, Kallapur SG, et al: The role of the multiple banded antigen of Ureaplasma parvum in intra-amniotic infection: major virulence factor or decoy? PLoS One 2012, 7:e29856

Figure 2. Lung inflammation and increased lung maturation after intraamniotic injection of Ureaplasma Parvum in sheep

Pregnant ewes were given intraamniotic injection of Ureaplasma Parvum (UP) 3d, 7d, 14d or 70d prior to delivery at 125 d gestation (term=150d). (A) Inflammatory cells (neutrophils + monocytes) in the broncho-alveolar lavage fluid (BALF) normalized to body weight. (B) Lung volumes measured at 40 cm H₂O pressure normalized to body weight. Intraamniotic injection of UP caused an initial lung inflammation followed by improved static compliance. (*p<0.05 vs. controls) Data from Kallapur SG, Kramer BW, Knox CL, et al: Chronic fetal exposure to Ureaplasma parvum suppresses innate immune responses in sheep. J Immunol 2011, 187:2688–95 and Collins JJ, Kallapur SG, Knox CL, et al: Inflammation in fetal sheep from intra-amniotic injection of Ureaplasma parvum. Am J Physiol Lung Cell Mol Physiol 2010, 299:L852–60