Genomic Analyses Identify Manganese Homeostasis as a Driver of Group B Streptococcal Vaginal Colonization.
Genomic Analyses Identify Manganese Homeostasis as a Driver of Group B Streptococcal Vaginal Colonization.
复制标题
作者：
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 (Mn2+)-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 ΔmtsA mutant strain and found by using inductively coupled plasma mass spectrometry that it exhibited decreased concentrations of intracellular Mn2+, confirming its involvement in Mn2+ acquisition. The ΔmtsA 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 ΔmtsA 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 Mn2+ homeostasis is an important process contributing to GBS survival in the FRT.
登录
查看更多内容
影响因子：
6.4
作者：
Grim KP;San Francisco B;Radin JN;Brazel EB;Kelliher JL;Párraga Solórzano PK;Kim PC;McDevitt CA;Kehl-Fie TE
通讯作者：
Kehl-Fie TE
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
6.4
作者：
Dale JL;Beckman KB;Willett JLE;Nilson JL;Palani NP;Baller JA;Hauge A;Gohl DM;Erickson R;Manias DA;Sadowsky MJ;Dunny GM
通讯作者：
Dunny GM
影响因子：
6.4
作者：
Burcham, Lindsey R.;Bath, Jade R.;Werlang, Caroline A.;Lyon, Laurie M.;Liu, Naoko;Evans, Christopher;Ribbeck, Katharina;Doran, Kelly S.
通讯作者：
Doran, Kelly S.
DOI：
10.1007/s10534-015-9826-z
发表时间：
2015-06
期刊：
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine
影响因子：
--
作者：
Eijkelkamp BA;McDevitt CA;Kitten T
通讯作者：
Kitten T