Inactivation of NMB0419 encoding a Sel1-like repeat (SLR) protein in Neisseria meningitidis is associated with differential expression of genes belonging to the Fur regulon and reduced intra-epithelial replication
File(s)
Accepted version
Author(s)
Kroll, J
Li, M-S
langford, P
Type
Journal Article
Abstract
Neisseria meningitidis
is a commensal microbe that colonizes the human
nasopharynx but occasionally invades the
bloodstream to cause life-threatening
infection.
N. meningitidis
MC58
NMB0419
encodes a Sel1-like repeat (SLR)-
containing protein, previously implicat
ed in invasion of epithelial cells. A gene-
regulatory function was revealed in
Escherichia coli
expressing plasmid-borne
NMB0419
showing significantly increased epi
thelial adherence compared to wild
type, due to increased expression of mannose-sensitive type 1 pili. While a
meningococcal
NMB0419
mutant did not have altered epithelial adherence, in a
transcriptome-wide comparison of wild type and an
NMB0419
mutant, a large
proportion of genes differentially regulated in the mutant were involved in iron
acquisition and metabolism. Fifty one and 38% of genes respectively up- and
down-regulated in the
NMB0419
mutant had previously been identified as being
induced and repressed by meningococcal Fur. An in vitro growth defect of the
NMB0419
mutant under iron-restriction was consistent with the down-regulation
of
tbpAB
and
hmbR
, while an intra-epithelial replication defect was consistent
with the down-regulation of
tonB
,
exbB
and
exbD
, based on a known phenotype
of a meningococcal
tonB
mutant. Disruption of the N-terminal NMB0419 signal
peptide, predicted to export the protein beyond the cytoplasmic membrane,
resulted in loss of functional traits in
N. meningitidis
and
E. coli
. Our study
indicates that the expression of
NMB0419
is associated with transcriptional
changes counterbalancing the regulatory function of Fur, offering a new
perspective on regulatory mechanisms involved in meningococcal interaction with epithelial cells, and suggests new insights into the roles of SLR-containing genes in other bacteria.
is a commensal microbe that colonizes the human
nasopharynx but occasionally invades the
bloodstream to cause life-threatening
infection.
N. meningitidis
MC58
NMB0419
encodes a Sel1-like repeat (SLR)-
containing protein, previously implicat
ed in invasion of epithelial cells. A gene-
regulatory function was revealed in
Escherichia coli
expressing plasmid-borne
NMB0419
showing significantly increased epi
thelial adherence compared to wild
type, due to increased expression of mannose-sensitive type 1 pili. While a
meningococcal
NMB0419
mutant did not have altered epithelial adherence, in a
transcriptome-wide comparison of wild type and an
NMB0419
mutant, a large
proportion of genes differentially regulated in the mutant were involved in iron
acquisition and metabolism. Fifty one and 38% of genes respectively up- and
down-regulated in the
NMB0419
mutant had previously been identified as being
induced and repressed by meningococcal Fur. An in vitro growth defect of the
NMB0419
mutant under iron-restriction was consistent with the down-regulation
of
tbpAB
and
hmbR
, while an intra-epithelial replication defect was consistent
with the down-regulation of
tonB
,
exbB
and
exbD
, based on a known phenotype
of a meningococcal
tonB
mutant. Disruption of the N-terminal NMB0419 signal
peptide, predicted to export the protein beyond the cytoplasmic membrane,
resulted in loss of functional traits in
N. meningitidis
and
E. coli
. Our study
indicates that the expression of
NMB0419
is associated with transcriptional
changes counterbalancing the regulatory function of Fur, offering a new
perspective on regulatory mechanisms involved in meningococcal interaction with epithelial cells, and suggests new insights into the roles of SLR-containing genes in other bacteria.
Date Issued
2017-03-06
Date Acceptance
2017-02-28
Citation
Infection and Immunity, 2017, 85 (5)
ISSN
1098-5522
Publisher
American Society for Microbiology
Journal / Book Title
Infection and Immunity
Volume
85
Issue
5
Copyright Statement
© 2017 American Society for Microbiology.
Sponsor
George John Livanos Charitable Trust
Grant Number
73/1/19625/TTC/SL
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Fur regulon
NMB0419
Neisseria meningitidis
Sel1-like repeat
epithelial cells
intracellular replication
iron acquisition
transcriptome
FALSE DISCOVERY RATE
ESCHERICHIA-COLI
EPITHELIAL-CELLS
PATHOGENIC NEISSERIA
BINDING PROTEINS
IRON
REGULATOR
IDENTIFICATION
FIMBRIAE
SURFACE
Bacterial Adhesion
Bacterial Proteins
Epithelial Cells
Escherichia coli
Gene Expression
Gene Expression Profiling
Gene Expression Regulation, Bacterial
Gene Knockout Techniques
Iron
Plasmids
Recombinant Proteins
Regulon
Repressor Proteins
Transcription Factors
06 Biological Sciences
11 Medical And Health Sciences
07 Agricultural And Veterinary Sciences
Microbiology
Publication Status
Published
Article Number
e00574-16