Streptococcus agalactiae cadD alleviates metal stress and promotes intracellular survival in macrophages and ascending infection during pregnancy
Perinatal infection with Streptococcus agalactiae , or Group B Streptococcus (GBS), is associated with preterm birth, neonatal sepsis, and stillbirth. Here, we study the interactions of GBS with macrophages, essential sentinel immune cells that defend the gravid reproductive tract. Transcriptional a...
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Published in | Nature communications Vol. 13; no. 1; pp. 5392 - 17 |
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Main Authors | , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
14.09.2022
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | Perinatal infection with
Streptococcus agalactiae
, or Group B
Streptococcus
(GBS), is associated with preterm birth, neonatal sepsis, and stillbirth. Here, we study the interactions of GBS with macrophages, essential sentinel immune cells that defend the gravid reproductive tract. Transcriptional analyses of GBS-macrophage co-cultures reveal enhanced expression of a gene encoding a putative metal resistance determinant,
cadD
. Deletion of
cadD
reduces GBS survival in macrophages, metal efflux, and resistance to metal toxicity. In a mouse model of ascending infection during pregnancy, the
ΔcadD
strain displays attenuated bacterial burden, inflammation, and cytokine production in gestational tissues. Furthermore, depletion of host macrophages alters cytokine expression and decreases GBS invasion in a
cadD
-dependent fashion. Our results indicate that GBS
cadD
plays an important role in metal detoxification, which promotes immune evasion and bacterial proliferation in the pregnant host.
Perinatal infection with Group B
Streptococcus
(GBS) is associated with preterm birth, neonatal sepsis, and stillbirth. Here, Korir et al. show that gene
cadD
, encoding a putative metal efflux transporter, is important for metal detoxification, immune evasion and bacterial proliferation in the pregnant host. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-022-32916-7 |