Streptococcus agalactiae cadD alleviates metal stress and promotes intracellular survival in macrophages and ascending infection during pregnancy

• Published in: Nature communications Vol. 13; no. 1; pp. 5392 - 17
• Main Authors: Korir, Michelle L., Doster, Ryan S., Lu, Jacky, Guevara, Miriam A., Spicer, Sabrina K., Moore, Rebecca E., Francis, Jamisha D., Rogers, Lisa M., Haley, Kathryn P., Blackman, Amondrea, Noble, Kristen N., Eastman, Alison J., Williams, Janice A., Damo, Steven M., Boyd, Kelli L., Townsend, Steven D., Henrique Serezani, C., Aronoff, David M., Manning, Shannon D., Gaddy, Jennifer A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.09.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/19; 14/28; 631/250/254; 631/326/41/2534; 631/326/41/88; 631/326/421; 64/60; Animals; Bacteria; Birth; Cytokines; Depletion; Detoxification; Efflux; Female; Gene deletion; Gene expression; Humanities and Social Sciences; Humans; Immune system; Infant, Newborn; Infections; Leukocyte Count; Macrophages; Macrophages - microbiology; Metals; Mice; multidisciplinary; Neonates; Perinatal infection; Pregnancy; Premature birth; Premature Birth - microbiology; Reproductive system; Science; Science (multidisciplinary); Sepsis; Stillbirth; Streptococcus; Streptococcus agalactiae; Streptococcus agalactiae - genetics; Streptococcus infections; Survival; Toxicity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-32916-7

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.