Comprehensive analysis of iron utilization by Mycobacterium tuberculosis.

Abstract:

:Iron is essential for nearly all bacterial pathogens, including Mycobacterium tuberculosis (Mtb), but is severely limited in the human host. To meet its iron needs, Mtb secretes siderophores, small molecules with high affinity for iron, and takes up iron-loaded mycobactins (MBT) and carboxymycobactins (cMBT), from the environment. Mtb is also capable of utilizing heme and hemoglobin which contain more than 70% of the iron in the human body. However, many components of these iron acquisition pathways are still unknown. In this study, a high-density transposon mutagenesis coupled with deep sequencing (TnSeq) showed that Mtb exhibits nearly opposite requirements for 165 genes in the presence of heme and hemoglobin versus MBT and cMBT as iron sources. The ESX-3 secretion system was assessed as essential for siderophore-mediated iron uptake and, surprisingly, also for heme utilization by Mtb. Predictions derived from the TnSeq analysis were validated by growth experiments with isogenic Mtb mutants. These results showed that (i) the efflux pump MmpL5 plays a dominant role in siderophore secretion, (ii) the Rv2047c protein is essential for growth of Mtb in the presence of mycobactin, and (iii) the transcriptional repressor Zur is required for heme utilization by Mtb. The novel genetic determinants of iron utilization revealed in this study will stimulate further experiments in this important area of Mtb physiology.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Zhang L,Hendrickson RC,Meikle V,Lefkowitz EJ,Ioerger TR,Niederweis M

doi

10.1371/journal.ppat.1008337

subject

Has Abstract

pub_date

2020-02-18 00:00:00

pages

e1008337

issue

2

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-19-02065

journal_volume

16

pub_type

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