The Regulatory Protein ChuP Connects Heme and Siderophore-Mediated Iron Acquisition Systems Required for Chromobacterium violaceum Virulence

• Published in: Frontiers in cellular and infection microbiology Vol. 12; p. 873536
• Main Authors: de Lima, Vinicius M, Batista, Bianca B, da Silva Neto, José F
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 11-05-2022
• Subjects: bacterial physiology; bacterial virulence; Cellular and Infection Microbiology; heme transporter; heme uptake; iron homeostasis; siderophores; Chromobacterium violaceum; heme transporter; bacterial virulence; bacterial physiology; iron homeostasis; heme uptake; siderophores
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2022.873536

is an environmental Gram-negative beta-proteobacterium that causes systemic infections in humans.
uses siderophore-based iron acquisition systems to overcome the host-imposed iron limitation, but its capacity to use other iron sources is unknown. In this work, we characterized ChuPRSTUV as a heme utilization system employed by
to explore an important iron reservoir in mammalian hosts, free heme and hemoproteins. We demonstrate that the
genes comprise a Fur-repressed operon that is expressed under iron limitation. The
operon potentially encodes a small regulatory protein (ChuP), an outer membrane TonB-dependent receptor (ChuR), a heme degradation enzyme (ChuS), and an inner membrane ABC transporter (ChuTUV). Our nutrition growth experiments using
deletion mutants revealed that, with the exception of
, all genes of the
operon are required for heme and hemoglobin utilization in
. The mutant strains without
displayed increased siderophore halos on CAS plate assays. Significantly, we demonstrate that ChuP connects heme and siderophore utilization by acting as a positive regulator of
and
, which encode the TonB-dependent receptors for the uptake of heme (ChuR) and the siderophore viobactin (VbuA). Our data favor a model of ChuP as a heme-binding post-transcriptional regulator. Moreover, our virulence data in a mice model of acute infection demonstrate that
uses both heme and siderophore for iron acquisition during infection, with a preference for siderophores over the Chu heme utilization system.