Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0038187 (
starvation
)
24,951
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Brucella abortus is the etiological agent of bovine brucellosis, an infectious disease of humans and cattle. Its pathogenesis is mainly based on its ability to survive and multiply inside macrophages. It has been demonstrated that if B. abortus
ferrochelatase
cannot incorporate iron into protoporphyrin IX to synthesize heme, the intracellular replication and virulence in mice is highly attenuated. Therefore, it can be hypothesized that the unavailability of iron could lead to the same attenuation in B. abortus pathogenicity. Thus, the purpose of this work was to obtain a B. abortus derivative unable to keep an internal iron pool and test its ability to replicate under iron limitation. To achieve this, we searched for iron-storage proteins in the genome of brucellae and found bacterioferritin (Bfr) as the sole ferritin encoded. Then, a B. abortus bfr mutant was built up and its capacity to store iron and replicate under iron limitation was investigated. Results indicated that B. abortus Bfr accounts for 70% of the intracellular iron content. Under iron limitation, the bfr mutant suffered from enhanced iron restriction with respect to wild type according to its growth retardation pattern, enhanced sensitivity to oxidative stress, accelerated production of siderophores, and altered expression of membrane proteins. Nonetheless, the bfr mutant was able to adapt and replicate even inside eukaryotic cells, indicating that B. abortus responds to internal iron
starvation
before sensing external iron availability. This suggests an active role of Bfr in controlling iron homeostasis through the availability of Bfr-bound iron.
...
PMID:Iron homeostasis in Brucella abortus: the role of bacterioferritin. 2104 46
Hydrogen peroxide pervades many natural environments, including the phagosomes that mediate cell-based immunity. Transcriptomic analysis showed that during protracted low-grade H(2)O(2) stress, Escherichia coli responds by activating both the OxyR defensive regulon and the Fur iron-
starvation
response. OxyR induced synthesis of two members of the nine-step heme biosynthetic pathway:
ferrochelatase
(HemH) and an isozyme of coproporphyrinogen III oxidase (HemF). Mutations that blocked either adaptation caused the accumulation of porphyrin intermediates, inadequate activation of heme enzymes, low catalase activity, defective clearance of H(2)O(2) and a failure to grow. Genetic analysis indicated that HemH induction is needed to compensate for iron sequestration by the mini-ferritin Dps. Dps activity protects DNA and proteins by limiting Fenton chemistry, but it interferes with the ability of HemH to acquire the iron that it needs to complete heme synthesis. HemF is a manganoprotein that displaces HemN, an iron-sulfur enzyme whose synthesis and/or stability is apparently problematic during H(2)O(2) stress. Thus, the primary responses to H(2)O(2), including the sequestration of iron, require compensatory adjustments in the mechanisms of iron-cofactor synthesis. The results support the growing evidence that oxidative stress is primarily an iron pathology.
...
PMID:The induction of two biosynthetic enzymes helps Escherichia coli sustain heme synthesis and activate catalase during hydrogen peroxide stress. 2566 92
The
Agrobacterium tumefaciens
ActSR two-component regulatory system is a member of a homologous group of global redox-responsive regulatory systems that adjust the expression of energy-consuming and energy-supplying metabolic pathways in order to maintain cellular redox balance. In this study, the transcriptional organization of the
hrpB-actSR
locus was determined and the effect of
actSR
system inactivation on stress resistance was investigated. It was found that
hrpB
is transcribed as a monocistronic mRNA and
actS
is transcribed along with
actR
as a bicistronic mRNA, while
actR
is also transcribed as a monocistronic message. Each message is initiated from a separate promoter. Inactivation of
actR
resulted in decreased resistance to membrane stress (sodium dodecyl sulfate), acid stress (pH 5.5), iron
starvation
(bipyridyl) and iron excess (FeCl
3
), and antibiotic stress (tetracycline and ciprofloxacin). Resistance to oxidative stress in the form of organic peroxide (cumene hydroperoxide) increased, while resistance to inorganic peroxide (H
2
O
2
) decreased. An
actR
insertion mutant displayed reduced catalase activity, even though transcription of
katA
and
catE
remained unchanged. Complementation of the
actR
inactivation mutant with plasmid-encoded
actR
or overexpression of
hemH
, encoding
ferrochelatase
, restored wild-type catalase activity and H
2
O
2
resistance levels. Gel mobility shift and
hemH
promoter
-lacZ
fusion results indicated that ActR is a positive regulator of
hemH
that binds directly to the
hemH
promoter region. Thus, inactivation of the
A. tumefaciens
ActSR system affects resistance to multiple stresses, including reduced resistance to H
2
O
2
resulting from a reduction in catalase activity due to reduced expression of
hemH
.
...
PMID:Inactivation of the
Agrobacterium tumefaciens
ActSR system affects resistance to multiple stresses with increased H
2
O
2
sensitivity due to reduced expression of
hemH
. 3133 84
