Foetal <i>Ureaplasma parvum</i> bacteraemia as a function of gestation‐dependent complement insufficiency: Evidence from a sheep model of pregnancy

Kemp, Matthew W.; Ahmed, Samrein B M; Beeton, Michael L.; Payne, Matthew S.; Saito, Masatoshi; Miura, Yoshio; Usuda, Haruo; Kallapur, Suhas G.; Kramer, Boris W.; Stock, Sarah; Jobe, Alan H.; Newnham, John P.; Spiller, O. Brad

doi:10.1111/aji.12599

Cited by 6 publications

(6 citation statements)

References 27 publications

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“…In accordance with several earlier studies ( 12 , 33 – 35 ), intra-amniotic infection following intra-amniotic UP administration was confirmed by the presence of UP in amniotic fluid during Cesarean section. No endogenous UP was detected in the amniotic fluid prior to inoculation (data not shown).…”

Section: Resultssupporting

confidence: 92%

Screening of Chorioamnionitis Using Volatile Organic Compound Detection in Exhaled Breath: A Pre-clinical Proof of Concept Study

et al. 2021

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Chorioamnionitis is a major risk factor for preterm birth and an independent risk factor for postnatal morbidity for which currently successful therapies are lacking. Emerging evidence indicates that the timing and duration of intra-amniotic infections are crucial determinants for the stage of developmental injury at birth. Insight into the dynamical changes of organ injury after the onset of chorioamnionitis revealed novel therapeutic windows of opportunity. Importantly, successful development and implementation of therapies in clinical care is currently impeded by a lack of diagnostic tools for early (prenatal) detection and surveillance of intra-amniotic infections. In the current study we questioned whether an intra-amniotic infection could be accurately diagnosed by a specific volatile organic compound (VOC) profile in exhaled breath of pregnant sheep. For this purpose pregnant Texel ewes were inoculated intra-amniotically with Ureaplasma parvum and serial collections of exhaled breath were performed for 6 days. Ureaplasma parvum infection induced a distinct VOC-signature in expired breath of pregnant sheep that was significantly different between day 0 and 1 vs. day 5 and 6. Based on a profile of only 15 discriminatory volatiles, animals could correctly be classified as either infected (day 5 and 6) or not (day 0 and 1) with a sensitivity of 83% and a specificity of 71% and an area under the curve of 0.93. Chemical identification of these distinct VOCs revealed the presence of a lipid peroxidation marker nonanal and various hydrocarbons including n-undecane and n-dodecane. These data indicate that intra-amniotic infections can be detected by VOC analyses of exhaled breath and might provide insight into temporal dynamics of intra-amniotic infection and its underlying pathways. In particular, several of these volatiles are associated with enhanced oxidative stress and undecane and dodecane have been reported as predictive biomarker of spontaneous preterm birth in humans. Applying VOC analysis for the early detection of intra-amniotic infections will lead to appropriate surveillance of these high-risk pregnancies, thereby facilitating appropriate clinical course of action including early treatment of preventative measures for pre-maturity-associated morbidities.

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Section: Resultssupporting

confidence: 92%

Screening of Chorioamnionitis Using Volatile Organic Compound Detection in Exhaled Breath: A Pre-clinical Proof of Concept Study

et al. 2021

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“…To investigate whether N-9-induced cervical epithelial challenge predisposes to ascending infection during pregnancy, we examined the magnitude and frequency of ascending bacterial infection following experimental vaginal inoculation of UP. UP was chosen as this is the most frequently isolated bacterial species associated with PTB 36 and the UP strain (HPA5) utilised has extensively been used in sheep models of intrauterine infection [37][38][39] .…”

Section: Resultsmentioning

confidence: 99%

“…Viable bacteria were quantified by 10-fold dilution (series of 15 µL in 135 µL) of inoculation stocks, vaginal flushes or amniotic fluid samples in USM in sterile 96-well plates (Elkay, Basingstoke, UK), sealed with clear adherent sealing film (Elkay, Basingstoke, UK) following incubation at 37°C for 48 h. For post-infection quantification, all values are calculated for bacterial load in the 15 µL of amniotic fluid or vaginal flush, for inoculating stocks values were calculated per mL of stock. A large-scale stock for inoculation was prepared by collecting mid-log phase growth UP after overnight incubation as previously described for experimental in utero pregnant sheep studies 39 . Inoculating stock was divided into 200 µL aliquots and sufficient aliquots were freshly thawed for the required number of mice to be infected in each batch of pregnant Fig.…”

Section: Methodsmentioning

confidence: 99%

Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice

et al. 2020

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Around 40% of preterm births are attributed to ascending intrauterine infection, and Ureaplasma parvum (UP) is commonly isolated in these cases. Here we present a mouse model of ascending UP infection that resembles human disease, using vaginal inoculation combined with mild cervical injury induced by a common spermicide (Nonoxynol-9, as a surrogate for any mechanism of cervical epithelial damage). We measure bacterial load in a non-invasive manner using a luciferase-expressing UP strain, and post-mortem by qPCR and bacterial titration. Cervical exposure to Nonoxynol-9, 24 h pre-inoculation, facilitates intrauterine UP infection, upregulates pro-inflammatory cytokines, and increases preterm birth rates from 13 to 28%. Our results highlight the crucial role of the cervical epithelium as a barrier against ascending infection. In addition, we expect the mouse model will facilitate further research on the potential links between UP infection and preterm birth.

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“…Chronic intrauterine Ureaplasma exposure appears to downregulate the host response to acute LPS exposure in the preterm sheep model [ 47 ]. Yet, the presence of Ureaplasma may be a function of prematurity as Kemp et al found that host bactericidal activity was directly correlated to gestational age, and the bactericidal activity appeared related to functional complement activity [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Airway Microbial Community Turnover Differs by BPD Severity in Ventilated Preterm Infants

et al. 2017

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Preterm birth exposes the developing lung to an environment with direct exposure to bacteria, often facilitated by endotracheal intubation. Despite evidence linking bacterial infections to the pathogenesis of bronchopulmonary dysplasia (BPD), systematic studies of airway microbiota are limited. The objective was to identify specific patterns of the early respiratory tract microbiome from tracheal aspirates of mechanically ventilated preterm infants that are associated with the development and severity of BPD. Infants with gestational age ≤34 weeks, and birth weight 500–1250g were prospectively enrolled. Mechanically ventilated infants had tracheal aspirate samples collected at enrollment, 7, 14, and 21 days of age. BPD was determined by modified NIH criteria with oxygen reduction tests; infants without BPD were excluded due to low numbers. Aspirates were processed for bacterial identification by 16S rRNA sequencing, and bacterial load by qPCR. Cross-sectional analysis was performed using 7 day samples and longitudinal analysis was performed from subjects with at least 2 aspirates. Microbiome analysis was performed on tracheal aspirates from 152 infants (51, 49, and 52 with mild, moderate, and severe BPD, respectively). Seventy-nine of the infants were included in the cross-sectional analysis and 94 in the longitudinal. Shannon Diversity, bacterial load, and relative abundance of individual taxa were not strongly associated with BPD status. Longitudinal analysis revealed that preterm infants who eventually developed severe BPD exhibited greater bacterial community turnover with age, acquired less Staphylococcus in the first days after birth, and had higher initial relative abundance of Ureaplasma. In conclusion, longitudinal changes in the airway microbial communities of mechanically ventilated preterm infants may be associated with BPD severity, whereas cross-sectional analysis of airway ecology at 7 days of age did not reveal an association with BPD severity. Further evaluation is necessary to determine whether the observed longitudinal changes are causal or in response to clinical management or other factors that lead to BPD.

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Foetal Ureaplasma parvum bacteraemia as a function of gestation‐dependent complement insufficiency: Evidence from a sheep model of pregnancy

Abstract: Ureaplasma bacteraemia in vivo was confined to early preterm lambs with low complement function, but Ureaplasma infection itself did not diminish complement levels.

Cited by 6 publications

References 27 publications

Screening of Chorioamnionitis Using Volatile Organic Compound Detection in Exhaled Breath: A Pre-clinical Proof of Concept Study

Screening of Chorioamnionitis Using Volatile Organic Compound Detection in Exhaled Breath: A Pre-clinical Proof of Concept Study

Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice

Airway Microbial Community Turnover Differs by BPD Severity in Ventilated Preterm Infants

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