Post-hypoxia Invasion of the fetal brain by multidrug resistant Staphylococcus

Zarate, Miguel; Rodriguez, Michelle; Chang, Eileen I.; Russell, Jordan T.; Arndt, Thomas; Richards, Elaine M.; Ocasio, Beronica A.; Aranda, Eva; Gordon, Elizabeth M.; Yu, Kevin; Neu, Josef; Keller‐Wood, Maureen; Triplett, Eric W.; Wood, Charles E.

doi:10.1038/s41598-017-06789-6

Cited by 18 publications

(48 citation statements)

References 38 publications

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“…); recently, we have linked these responses to the appearance of bacterial strains in the cerebral cortex and placenta (Zarate et al . ). In the present study, interestingly, we also detected bacterial 16S expression in the fetal brain in all four groups (i.e.…”

Section: Discussionmentioning

confidence: 97%

“…During HH, maternal cortisol levels rises substantially (Chang & Wood, ) and, once released, we speculate that it might have a particular effect on the placental circulation leading to the release of bacteria previously harbored in the fetal membranes (Zarate et al . ). These microorganisms could be the potential factor for the inflammation response observed in fetal brain tissues and kidneys (Chang et al .…”

Section: Discussionmentioning

confidence: 97%

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Effects of ketamine on the fetal transcriptomic response to umbilical cord occlusion: comparison with hypoxic hypoxia in the cerebral cortex

Zarate

Chang

Wood

2018

The Journal of Physiology

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Umbilical cord occlusion (UCO) is known to cause neurological disorders in the neonate. Previously, we have reported that hypoxic hypoxia (HH) stimulates the appearance of bacteria in the fetal brain and upregulates the expression of inflammatory markers in fetal cerebral cortex (CTX) and also that ketamine attenuates these responses. In the present study, we aimed to test the hypothesis that UCO, similar to HH, produces an inflammatory response in the fetal CTX and also that treatment with ketamine reduces these effects. In chronically instrumented fetal sheep (∼125 days), 30 min of partial UCO decreased fetal levels by ∼50%. Half of the fetuses received ketamine (3 mg kg ) 10 min prior to UCO (n = 4 per group). Fetal brains were collected 1 and 24 h after the experiment and mRNA was extracted and hybridized for microarray analyses. Differentially-expressed genes were analysed for significant association with gene ontologies and pathways. After 1 h, UCO upregulated nucleic acid processing and chromatin modification and downregulated metabolic processes compared to control. After 24 h, UCO upregulated metabolic and protein modification processes. Ketamine produced minimal effects. UCO did not alter the abundance of bacterial DNA in fetal brain, nor did it upregulate inflammation pathways compared to HH. We conclude that UCO produced time-dependent responses that did not include bacterial invasion or upregulation of inflammation pathways in fetal CTX. This contrasts with the response to HH, which resulted in the appearance of bacteria in the CTX and upregulated inflammation pathways. These responses in fetal CTX to oxygen deprivation are therefore modified by the maternal or placental response to the stimulus.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Effects of ketamine on the fetal transcriptomic response to umbilical cord occlusion: comparison with hypoxic hypoxia in the cerebral cortex

Zarate

Chang

Wood

2018

The Journal of Physiology

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“…Using pregnant ewes, Zarate and colleagues recently demonstrated that maternal and/or fetal hypoxic stress later in pregnancy upregulates neuro-immune pathways associated with LPS stimulation 65 . Under these conditions, this group detected live antibiotic-resistant Staphylococcus simulans in the placenta and fetal brain, suggesting that specific physiological changes associated with hypoxic stress, such as increased blood flow and barrier permeability, can promote the passage of maternal bacteria across the placenta and fetal blood-brain barrier 65 . Similarly, maternal stress levels or other unknown physiological changes during pregnancy may explain the presence of R. insidiosa in the human placenta.…”

Section: Discussionmentioning

confidence: 99%

Functional characterization ofRalstonia insidiosa, a bona fide resident at the maternal-fetal interface

Parnell

Willsey

Joshi

et al. 2019

Preprint

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Controversy about whether there are microbes in the placenta and if they have any functional importance during pregnancy and for neonatal health is ongoing. Previous work has demonstrated that the basal plate (BP), comprising maternal and fetal derived cells harbors intracellular bacteria. 16S sequencing and bacterial species-specific analysis of term placentas revealed that the gram-negative bacillus Ralstonia insidiosa, native to aqueous environments and an effective biofilm promoter, comprises the most abundant species in the BP. Here, we demonstrate whether R. insidiosa cells home to a particular niche in the BP, how they may arrive there, and whether they are associated with adverse outcomes. We developed methods to detect and study cell-specific localization of R.insidiosa using ex vivo and in vitro models. Additionally, we studied potential routes of R.insidiosa entry into the placenta. We show that R. insidiosa is a bona fide resident in human placental BP. It can access trophoblast cells in culture and within basal plate tissues where it localizes to intracellular single-membrane vacuoles and can replicate.However, the presence of R. insidiosa does not cause cell death and does not induce a pro-inflammatory immune response suggesting that it is not harmful in and of itself.Finally, we show that in a pregnant mouse model, R. insidiosa traffics to the placenta via the intrauterine route but does not induce preterm labor or preterm birth. Together, our findings provide a foundation for understanding non-pathogenic placental cell-microbe interactions and the functional importance of R. insidiosa in placental health and physiology.

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“…Interestingly, it was recently shown that hypoxia promotes bacterial entry to the brain, suggesting synergy between different insults that should be considered in future studies (Zarate et al . ).…”

Section: Central Nervous System Barriersmentioning

confidence: 97%

The myth of the immature barrier systems in the developing brain: role in perinatal brain injury

Mallard

Vexler

2018

The Journal of Physiology

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Central nervous system homeostasis is maintained by cellular barriers that protect the brain from external environmental changes and protect the CNS from harmful molecules and pathogens in the blood. Historically, for many years these barriers were thought of as immature, with limited functions, during brain development. In this review, we will present advances in the understanding of the barrier systems during development and evidence to show that in fact the barriers serve many important neurodevelopmental functions and that fetal and newborn brains are well protected. We will also discuss how ischaemic injury or systemic inflammation may breach the integrity of the barriers in the developing brain.

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Post-hypoxia Invasion of the fetal brain by multidrug resistant Staphylococcus

Cited by 18 publications

References 38 publications

Effects of ketamine on the fetal transcriptomic response to umbilical cord occlusion: comparison with hypoxic hypoxia in the cerebral cortex

Effects of ketamine on the fetal transcriptomic response to umbilical cord occlusion: comparison with hypoxic hypoxia in the cerebral cortex

Functional characterization ofRalstonia insidiosa, a bona fide resident at the maternal-fetal interface

The myth of the immature barrier systems in the developing brain: role in perinatal brain injury

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