Genomic Analyses Identify Manganese Homeostasis as a Driver of Group B Streptococcal Vaginal Colonization

Lindsey R. Burcham, Madeline S. Akbari, Norhan Alhajjar, Rebecca A. Keogh, Jana N. Radin, Thomas E. Kehl-Fie, Ashton T. Belew, Najib M. El-Sayed, Kevin S. McIver, Kelly S. Doran

Research output: Contribution to journalArticlepeer-review

Abstract

Group B Streptococcus (GBS) is associated with severe infections in utero and in newborn populations, including pneumonia, sepsis, and meningitis. GBS vaginal colonization of the pregnant mother is an important prerequisite for transmission to the newborn and the development of neonatal invasive disease; however, our understanding of the factors required for GBS persistence and ascension in the female reproductive tract (FRT) remains limited. Here, we utilized a GBS mariner transposon (Krmit) mutant library previously developed by our group and identified underrepresented mutations in 535 genes that contribute to survival within the vaginal lumen and colonization of vaginal, cervical, and uterine tissues. From these mutants, we identified 47 genes that were underrepresented in all samples collected, including mtsA, a component of the mtsABC locus, encoding a putative manganese (Mn21)-dependent ATP-binding cassette transporter. RNA sequencing analysis of GBS recovered from the vaginal tract also revealed a robust increase of mtsA expression during vaginal colonization. We engineered an DmtsA mutant strain and found by using inductively coupled plasma mass spectrometry that it exhibited decreased concentrations of intracellular Mn21, confirming its involvement in Mn21 acquisition. The DmtsA mutant was significantly more susceptible to the metal chelator calprotectin and to oxidative stressors, including both H2O2 and paraquat, than wild-type (WT) GBS. We further observed that the DmtsA mutant strain exhibited a significant fitness defect in comparison to WT GBS in vivo by using a murine model of vaginal colonization. Taken together, these data suggest that Mn21 homeostasis is an important process contributing to GBS survival in the FRT.

Original languageEnglish (US)
JournalmBio
Volume13
Issue number3
DOIs
StatePublished - Jun 2022

Keywords

  • Group B Streptococcus
  • intrauterine infection
  • manganese
  • vaginal colonization

ASJC Scopus subject areas

  • Virology
  • Microbiology

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