Transcriptomic Analysis of Streptococcus pyogenes Colonizing the Vaginal Mucosa Identifies hupY, an MtsR-Regulated Adhesin Involved in Heme Utilization

mBio

Laura C. C. Cook¹  Jorge Andrade²  Yan Li³  Zehava Eichenbaum⁴  Nilanjana Chatterjee⁴  Michael J. Federle⁵ 

[1] Binghamton Biofilm Research Center, Department of Biology, Binghamton University, Binghamton, New York, USA;Center for Research Informatics and Department of Pediatrics, Biological Sciences Division, The University of Chicago, Chicago, Illinois, USA;Center for Research Informatics, The University of Chicago, Chicago, Illinois, USA;Department of Biology, Georgia State University, Atlanta, Georgia, USA;Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois, USA;

关键词: colonization;    Streptococcus;    adherence;    heme;    iron uptake;   

DOI  :  10.1128/mBio.00848-19

来源: DOAJ

【 摘 要 】

ABSTRACT Streptococcus pyogenes (group A streptococcus [GAS]) is a serious human pathogen with the ability to colonize mucosal surfaces such as the nasopharynx and vaginal tract, often leading to infections such as pharyngitis and vulvovaginitis. We present genome-wide transcriptome sequencing (RNASeq) data showing the transcriptomic changes GAS undergoes during vaginal colonization. These data reveal that the regulon controlled by MtsR, a master metal regulator, is activated during vaginal colonization. This regulon includes two genes highly expressed during vaginal colonization, hupYZ. Here we show that HupY binds heme in vitro, affects intracellular concentrations of iron, and is essential for proper growth of GAS using hemoglobin or serum as the sole iron source. HupY is also important for murine vaginal colonization of both GAS and the related vaginal colonizer and pathogen Streptococcus agalactiae (group B streptococcus [GBS]). These data provide essential information on the link between metal regulation and mucosal colonization in both GAS and GBS. IMPORTANCE Colonization of the host requires the ability to adapt to an environment that is often low in essential nutrients such as iron. Here we present data showing that the transcriptome of the important human pathogen Streptococcus pyogenes shows extensive remodeling during in vivo growth, resulting in, among many other differentially expressed genes and pathways, a significant increase in genes involved in acquiring iron from host heme. Data show that HupY, previously characterized as an adhesin in both S. pyogenes and the related pathogen Streptococcus agalactiae, binds heme and affects intracellular iron concentrations. HupY, a protein with no known heme binding domains, represents a novel heme binding protein playing an important role in bacterial iron homeostasis as well as vaginal colonization.

【 授权许可】

Unknown