scholarly journals CtaM Is Required for Menaquinol Oxidaseaa3Function inStaphylococcus aureus

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Neal D. Hammer ◽  
Lici A. Schurig-Briccio ◽  
Svetlana Y. Gerdes ◽  
Robert B. Gennis ◽  
Eric P. Skaar
Keyword(s):  
Staphylococcus Aureus ◽  
Electron Transport ◽  
Electron Transport Chain ◽  
Molecular Mechanisms ◽  
Carbon Sources ◽  
Spectroscopic Studies ◽  
Uncharacterized Protein ◽  
Terminal Oxidases ◽  
Transport Chain ◽  
Genes Encoding

ABSTRACTStaphylococcus aureusis the leading cause of skin and soft tissue infections, bacteremia, osteomyelitis, and endocarditis in the developed world. The ability ofS. aureusto cause substantial disease in distinct host environments is supported by a flexible metabolism that allows this pathogen to overcome challenges unique to each host organ. One feature of staphylococcal metabolic flexibility is a branched aerobic respiratory chain composed of multiple terminal oxidases. Whereas previous biochemical and spectroscopic studies reported the presence of three different respiratory oxygen reductases (otype,bdtype, andaa3type), the genome contains genes encoding only two respiratory oxygen reductases,cydABandqoxABCD. Previous investigation showed thatcydABandqoxABCDare required to colonize specific host organs, the murine heart and liver, respectively. This work seeks to clarify the relationship between the genetic studies showing the unique roles of thecydABandqoxABCDin virulence and the respiratory reductases reported in the literature. We establish that QoxABCD is anaa3-type menaquinol oxidase but that this enzyme is promiscuous in that it can assemble as abo3-type menaquinol oxidase. However, thebo3form of QoxABCD restricts the carbon sources that can support the growth ofS. aureus. In addition, QoxABCD function is supported by a previously uncharacterized protein, which we have named CtaM, that is conserved in aerobically respiringFirmicutes. In total, these studies establish the heme A biosynthesis pathway inS. aureus, determine that QoxABCD is a typeaa3menaquinol oxidase, and reveal CtaM as a new protein required for typeaa3menaquinol oxidase function in multiple bacterial genera.IMPORTANCEStaphylococcus aureusrelies upon the function of two terminal oxidases, CydAB and QoxABCD, to aerobically respire and colonize distinct host tissues. Previous biochemical studies support the conclusion that a third terminal oxidase is also present. We establish the components of theS. aureuselectron transport chain by determining the heme cofactors that interact with QoxABCD. This insight explains previous observations by revealing that QoxABCD can utilize different heme cofactors and confirms that the electron transport chain ofS. aureusis comprised of two terminal menaquinol oxidases. In addition, a newly identified protein, CtaM, is found to be required for the function of QoxABCD. These results provide a more complete assessment of the molecular mechanisms that support staphylococcal respiration.

scholarly journals The oxidation of nicotinic acid by Pseudomonas ovalis Chester. The terminal oxidase

1972 ◽  
Vol 129 (3) ◽  
pp. 755-761 ◽  
Author(s):  
M. V. Jones ◽  
D. E. Hughes
Keyword(s):  
Electron Transport ◽  
Nicotinic Acid ◽  
Electron Transport Chain ◽  
Acid Oxidase ◽  
Terminal Oxidase ◽  
Difference Spectra ◽  
Terminal Oxidases ◽  
Cytochrome O ◽  
Transport Chain ◽  
Terminal Oxidation

In cell-free extracts of Pseudomonas ovalis nicotinic acid oxidase is confined to the wallmembrane fraction. It is associated with an electron-transport chain comprising b- and c-type cytochromes only, differing proportions of which are reduced by nicotinate and NADH. CO difference-spectra show two CO-binding pigments, cytochrome o (absorption maximum at 417nm) and another component absorbing maximally at 425nm. Cytochrome o is not reduced by NADH or by succinate but is by nicotinate, which can also reduce the ‘425’ CO-binding pigment. The effects of inhibitors of terminal oxidation support the idea of two terminal oxidases and a scheme involving the ‘425’ CO-binding pigment and the other components of the electron-transport chain is proposed.

scholarly journals Exploration of Nitrate Reductase Metabolic Pathway inCorynebacterium pseudotuberculosis

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Sintia Almeida ◽  
Cassiana Sousa ◽  
Vinícius Abreu ◽  
Carlos Diniz ◽  
Elaine M. S. Dorneles ◽  
...  
Keyword(s):  
Electron Transport ◽  
Nitrate Reductase ◽  
Virulence Factors ◽  
Electron Transport Chain ◽  
Drug Targets ◽  
Carbon Sources ◽  
The Other ◽  
Ecological Niches ◽  
Transport Chain ◽  
In Silico Methods

Based on the ability of nitrate reductase synthesis,Corynebacterium pseudotuberculosisis classified into two biovars: Ovis and Equi. Due to the presence of nitrate reductase, the Equi biovar can survive in absence of oxygen. On the other hand, Ovis biovar that does not have nitrate reductase is able to adapt to various ecological niches and can grow on certain carbon sources. Apart from these two biovars, some other strains are also able to carry out the reduction of nitrate. The enzymes that are involved in electron transport chain are also identified by in silico methods. Findings about pathogen metabolism can contribute to the identification of relationship between nitrate reductase and theC. pseudotuberculosispathogenicity, virulence factors, and discovery of drug targets.

Growth-inhibitory activities of some 1,4-naphthoquinones and related compounds on Staphylococcus aureus and Escherichia coli

1968 ◽  
Vol 14 (6) ◽  
pp. 661-666 ◽  
Author(s):  
G. J. Leahy ◽  
D. J Currie ◽  
H. L. Holmes ◽  
J. R. Maltman
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Electron Transport ◽  
Electron Transport Chain ◽  
Growth Inhibitory ◽  
Transport Chain ◽  
Half Wave ◽  
Inhibitory Activities ◽  
Related Compounds

Growth-inhibitory activities of some or all of 98 1,4-naphthoquinones and 16 related compounds on Escherichia coli and two strains of Staphylococcus aureus were determined alone or in combination. These values, when plotted against their polarographic half-wave potentials and those of their C2-n-butylthio analogs support the hypothesis that these compounds, or the products resulting from their reaction with a protein nucleophile, function by short-circuiting one or other of the quinones present in the electron-transport chain.

scholarly journals Effects of Aging on Activities of Mitochondrial Electron Transport Chain Complexes and Oxidative Damage in Rat Heart

2011 ◽  
pp. 281-289 ◽  
Author(s):  
Z. TATARKOVÁ ◽  
S. KUKA ◽  
P. RAČAY ◽  
J. LEHOTSKÝ ◽  
D. DOBROTA ◽  
...  
Keyword(s):  
Electron Transport ◽  
Oxidative Damage ◽  
Electron Transport Chain ◽  
Molecular Mechanisms ◽  
Thiol Group ◽  
Mitochondrial Electron Transport Chain ◽  
Age Related ◽  
Transport Chain ◽  
Old Rats ◽  
Major Factors

Mitochondrial dysfunction and accumulation of oxidative damage have been implicated to be the major factors of aging. However, data on age-related changes in activities of mitochondrial electron transport chain (ETC) complexes remain controversial and molecular mechanisms responsible for ETC dysfunction are still largely unknown. In this study, we examined the effect of aging on activities of ETC complexes and oxidative damage to proteins and lipids in cardiac mitochondria from adult (6-month-old), old (15-month-old) and senescent (26-month-old) rats. ETC complexes I-IV displayed different extent of inhibition with age. The most significant decline occurred in complex IV activity, whereas complex II activity was unchanged in old rats and was only slightly reduced in senescent rats. Compared to adult, old and senescent rat hearts had significantly higher levels of malondialdehyde, 4-hydroxynonenal (HNE) and dityrosine, while thiol group content was reduced. Despite marked increase in HNE content with age (25 and 76 % for 15- and 26-month-old rats, respectively) Western blot analysis revealed only few HNE-protein adducts. The present study suggests that non-uniform decline in activities of ETC complexes is due, at least in part, to mitochondrial oxidative damage; however, lipid peroxidation products appear to have a limited impact on enzyme functions.

scholarly journals Induction of Terminal Oxidases of Electron Transport Chain in Broccoli Heads under Controlled Atmosphere Storage

Foods ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 380 ◽  
Author(s):  
Yoshio Makino ◽  
Jun Inoue ◽  
Hsiao-Wen Wang ◽  
Masatoshi Yoshimura ◽  
Kensaku Maejima ◽  
...  
Keyword(s):  
Electron Transport ◽  
Mass Loss ◽  
Electron Transport Chain ◽  
Biological Properties ◽  
Controlled Atmosphere ◽  
High Co2 ◽  
Terminal Oxidases ◽  
Transport Chain ◽  
Atmosphere Storage ◽  
Oxygen Isotope Discrimination

Controlled atmosphere (CA) storage, that is, at low O2 and high CO2 concentrations, effectively extends the shelf life of horticultural products. The influence of CA storage (O2/CO2: 2.5%/6.0% or 2.5%/0.0%) and in normal air (both at 1 °C for 21 d) on the physicochemical (O2 uptake, mass loss and L-ascorbate) and biological properties of broccoli (Brassica oleracea var. italica, Plenck, 1794) via amounts and activities of terminal oxidases of the electron transport chain was investigated. Mass loss, a sensitive index of freshness for broccoli heads under CA, was significantly lower under CA than under normoxia (p < 0.05). Mass loss was depressed 7 d earlier under CA, including 6.0% CO2 than under CA without CO2. High CO2 effectively depressed the degradation of L-ascorbate. During storage, the activity of the alternative oxidase (AOX) was lower under CA than in normal air (p < 0.05), while the amount of cytochrome c oxidase (COX), and the AOX/COX activity ratio (based on oxygen isotope discrimination), were not affected during storage. Our results indicate that CA storage effectively retained the freshness of broccoli heads by depressing the induction of AOX. However, depression of AOX amount was not associated with CO2 around broccoli heads.

scholarly journals Terminal Respiratory Oxidases: A Targetables Vulnerability of Mycobacterial Bioenergetics?

2020 ◽  
Vol 10 ◽  
Author(s):  
Sapna Bajeli ◽  
Navin Baid ◽  
Manjot Kaur ◽  
Ganesh P. Pawar ◽  
Vinod D. Chaudhari ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Electron Transport ◽  
Molecular Oxygen ◽  
Electron Transport Chain ◽  
Drug Targets ◽  
Atp Synthesis ◽  
Terminal Oxidase ◽  
Terminal Oxidases ◽  
Transport Chain ◽  
Synthase Inhibitor

Recently, ATP synthase inhibitor Bedaquiline was approved for the treatment of multi-drug resistant tuberculosis emphasizing the importance of oxidative phosphorylation for the survival of mycobacteria. ATP synthesis is primarily dependent on the generation of proton motive force through the electron transport chain in mycobacteria. The mycobacterial electron transport chain utilizes two terminal oxidases for the reduction of oxygen, namely the bc1-aa3 supercomplex and the cytochrome bd oxidase. The bc1-aa3 supercomplex is an energy-efficient terminal oxidase that pumps out four vectoral protons, besides consuming four scalar protons during the transfer of electrons from menaquinone to molecular oxygen. In the past few years, several inhibitors of bc1-aa3 supercomplex have been developed, out of which, Q203 belonging to the class of imidazopyridine, has moved to clinical trials. Recently, the crystal structure of the mycobacterial cytochrome bc1-aa3 supercomplex was solved, providing details of the route of transfer of electrons from menaquinone to molecular oxygen. Besides providing insights into the molecular functioning, crystal structure is aiding in the targeted drug development. On the other hand, the second respiratory terminal oxidase of the mycobacterial respiratory chain, cytochrome bd oxidase, does not pump out the vectoral protons and is energetically less efficient. However, it can detoxify the reactive oxygen species and facilitate mycobacterial survival during a multitude of stresses. Quinolone derivatives (CK-2-63) and quinone derivative (Aurachin D) inhibit cytochrome bd oxidase. Notably, ablation of both the two terminal oxidases simultaneously through genetic methods or pharmacological inhibition leads to the rapid death of the mycobacterial cells. Thus, terminal oxidases have emerged as important drug targets. In this review, we have described the current understanding of the functioning of these two oxidases, their physiological relevance to mycobacteria, and their inhibitors. Besides these, we also describe the alternative terminal complexes that are used by mycobacteria to maintain energized membrane during hypoxia and anaerobic conditions.

scholarly journals Propofol induces a metabolic switch to glycolysis and cell death in a mitochondrial electron transport chain-dependent manner

2017 ◽  
Author(s):  
Chisato Sumi ◽  
Akihisa Okamoto ◽  
Hiromasa Tanaka ◽  
Kenichiro Nishi ◽  
Munenori Kusunoki ◽  
...  
Keyword(s):  
Cell Death ◽  
Electron Transport ◽  
Mitochondrial Function ◽  
Electron Transport Chain ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Propofol Infusion Syndrome ◽  
Metabolic Switch ◽  
Transport Chain

AbstractThe intravenous anesthetic propofol (2,6-diisopropylphenol) has been used for the induction and maintenance of anesthesia in operating rooms and for sedation in intensive care units. Although there is no widely accepted definition of propofol infusion syndrome (PRIS), PRIS is defined as the development of metabolic acidosis, rhabdomyolysis, hyperkalemia, hepatomegaly, renal failure, arrhythmia, and progressive cardiac failure. In vitro evidence suggests that PRIS is related to the impaired mitochondrial function. There are indications that preexisting mitochondrial disorders predispose to PRIS. However, the precise molecular mechanisms, including mitochondrial defects and a metabolic conversion by propofol, are largely unknown as yet. To elucidate the underlying cellular and molecular mechanisms of PRIS, we investigated the effects of propofol on the cellular metabolic mode and cell death. We demonstrated that clinically relevant concentrations of propofol, used within a clinically relevant exposure time, suppressed the mitochondrial function, caused the generation of reactive oxygen species, and induced a metabolic switch, from oxidative phosphorylation to glycolysis, by targeting complexes I and III of mitochondria. The data also indicated that a predisposition to mitochondrial dysfunction, caused by a genetic mutation or pharmacological suppression of the electron transport chain by biguanides such as metformin and phenformin, promoted the cell death and caspase activation induced by propofol.

Downregulation of diaphragm electron transport chain and glycolytic enzyme gene expression in sepsis

2005 ◽  
Vol 99 (3) ◽  
pp. 1120-1126 ◽  
Author(s):  
Leigh Ann Callahan ◽  
Gerald S. Supinski
Keyword(s):  
Gene Expression ◽  
Energy Metabolism ◽  
Electron Transport ◽  
Atp Synthase ◽  
Electron Transport Chain ◽  
Cellular Energy ◽  
Protein Levels ◽  
Cellular Energy Metabolism ◽  
Transport Chain ◽  
Genes Encoding

Cellular energy metabolism is altered in sepsis as a consequence of dysfunction of mitochondrial electron transport and glycolytic pathways. The purpose of the present study was to determine whether sepsis is associated with compensatory increases in gene expression of electron transport chain and glycolytic pathway proteins or, alternatively, whether gene expression decreases in sepsis, contributing to abnormalities in energy metabolism. Studies were performed using diaphragms from control and endotoxin-treated (8 mg·kg−1·day−1) rats; at 48 h after endotoxin administration, animals were killed. Microarrays and RNAse protection assays were used to assess the expression of several electron transport chain components (cytochrome- c oxidase subunits Cox 5A, Cox 5B, and Cox 6A, ATP synthase, and ATP synthase subunit 5B) and of the rate-limiting enzyme for glycolysis, phosphofructokinase (PFK). Western blotting was used to assess protein levels for these electron transport chain subunits and PFK. Activity assays were used to assess electron transport chain and phosphofructokinase function. We found that sepsis evoked 1) a downregulation of genes encoding all examined electron transport chain components (e.g., cytochrome- c oxidase 5A decreased 45 + 7%, P < 0.01) and PFK ( P < 0.001), 2) reductions in protein levels for these electron transport chain subunits and PFK ( P < 0.05 for each), and 3) decreases in mitochondrial state 3 respiration rates and phosphofructokinase enzyme activity ( P < 0.01 for each comparison). We speculate that these sepsis-induced reductions in the expression of genes encoding critical electron transport and glycolytic proteins contribute to the development and persistence of sepsis-induced abnormalities in cellular energy metabolism.

scholarly journals Small-Colony Variant Selection as a Survival Strategy for Staphylococcus aureus in the Presence of Pseudomonas aeruginosa

2009 ◽  
Vol 75 (21) ◽  
pp. 6910-6912 ◽  
Author(s):  
Lalitha Biswas ◽  
Raja Biswas ◽  
Martin Schlag ◽  
Ralph Bertram ◽  
Friedrich Götz
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Electron Transport ◽  
Electron Transport Chain ◽  
Survival Strategy ◽  
Variant Selection ◽  
Small Colony Variant ◽  
Transport Chain ◽  
Small Colony ◽  
Selection Of

ABSTRACT Previously it has been demonstrated that Staphylococcus aureus is sensitive toward Pseudomonas-secreted exotoxins, which preferentially target the electron transport chain in staphylococci. Here it is shown that a subpopulation of S. aureus survives these respiratory toxins of P seudomonas aeruginosa by selection of the small-colony variant (SCV) phenotype. Purified pyocyanin alone causes the same effect. A hem B mutant of S. aureus survives cocultivation with P. aeruginosa without a decrease in CFU.

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