AUTHOR=Song Yingli , Zhang Xiaolan , Cai Minghui , Lv Chunmei , Zhao Yuan , Wei Deqin , Zhu Hui 

TITLE=The Heme Transporter HtsABC of Group A Streptococcus Contributes to Virulence and Innate Immune Evasion in Murine Skin Infections

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.01105

DOI=10.3389/fmicb.2018.01105

ISSN=1664-302X

ABSTRACT=<p>Group A <italic>Streptococcus</italic> (GAS) requires iron for growth, and heme is an important source of iron for GAS. Streptococcus heme transporter A (HtsA) is the lipoprotein component of the GAS heme-specific ABC transporter (HtsABC). The objective of this study is to examine the contribution of HtsABC to virulence and host interaction of hypervirulent M1T1 GAS using an isogenic <italic>htsA</italic> deletion mutant (Δ<italic>htsA</italic>). The <italic>htsA</italic> deletion exhibited a significantly increased survival rate, reduced skin lesion size, and reduced systemic GAS dissemination in comparison to the wild type strain. The <italic>htsA</italic> deletion also decreased the GAS adhesion rate to Hep-2 cells, the survival in human blood and rat neutrophils, and increased the production of cytokine IL-1β, IL-6, and TNF-α levels in air pouch exudate of a mouse model of subcutaneous infection. Complementation of Δ<italic>htsA</italic> restored the wild type phenotype. These findings support that the <italic>htsA</italic> gene is required for GAS virulence and that the <italic>htsA</italic> deletion augments host innate immune responses.</p>