Genome-wide assessment of Streptococcus agalactiae genes required for fitness in human whole blood and plasma.

Zhu, Luchang; Yerramilli, Prasanti; Pruitt, Layne; Saavedra, Matthew Ojeda; Cantu, Concepcion C; Olsen, Randall J; Beres, Stephen B; Waller, Andrew S; Musser, James M

Streptococcus agalactiae (group B streptococcus, GBS) is a common cause of bacteremia and sepsis in newborns, pregnant women and immunocompromised patients. The molecular mechanisms used by GBS to survive and proliferate in blood are not well understood. Here, using a highly virulent GBS strain and Transposon Directed Insertion-site Sequencing (TraDIS), we performed genome-wide screens to discover novel GBS genes required for bacterial survival in human whole blood and plasma. The screen identified 85 and 41 genes that are required for GBS growth in whole blood and plasma, respectively. A common set of 29 genes was required in both whole blood and plasma. Targeted gene deletion confirmed that (i) genes encoding methionine transporter (metP) and manganese transporter (mtsA) are crucial for GBS survival in whole blood and plasma, (ii) gene W903_1820 encoding a small multi-drug export family protein contributes significantly to GBS survival in whole blood, (iii) the shikimate pathway gene aroA is essential for GBS growth in whole blood and plasma, and (iv) deletion of srr1 encoding a fibrinogen-binding adhesin increases GBS survival in whole blood. Our findings provide new insight into the GBS-host interactions in human blood.