scholarly journals New Mitochondrial Targets in Fungal Pathogens

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Daniel Murante ◽  
Deborah A. Hogan
Keyword(s):  
Electron Transport Chain ◽  
Fungal Pathogens ◽  
Phylogenetic Group ◽  
Eukaryotic Cells ◽  
Respiratory Metabolism ◽  
Human Pathogens ◽  
Model Species ◽  
Content Type ◽  
Transport Chain ◽  
Microbiological Assays

ABSTRACT In eukaryotic cells, mitochondria are responsible for the synthesis of ATP using power generated by the electron transport chain (ETC). While much of what is known about mitochondria has been gained from a study of a small number of model species, including the yeast Saccharomyces cerevisiae, the general mechanisms of mitochondrial respiration have been recognized as being highly conserved across eukaryotes. Now, Sun et al. (N. Sun, R. S. Parrish, R. A. Calderone, and W. A. Fonzi, mBio 10:e00300-19, 2019, https://doi.org/10.1128/mBio.00300-19) take the next steps in understanding mitochondrial function by identifying proteins that are unique to a smaller phylogenetic group of microbes. Using the combination of in silico, biochemical, and microbiological assays, Sun and colleagues identified seven genes that are unique to the CTG fungal clade, which contains multiple important human pathogens, including Candida albicans, and showed that they are required for full ETC function during respiratory metabolism. Because respiratory metabolism is critical for fungal pathogenesis, these clade-specific mitochondrial factors may represent novel therapeutic targets.

scholarly journals Unique, Diverged, and Conserved Mitochondrial Functions InfluencingCandida albicansRespiration

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Nuo Sun ◽  
Rebecca S. Parrish ◽  
Richard A. Calderone ◽  
William A. Fonzi
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Complex I ◽  
Electron Transport Chain ◽  
Complex Iii ◽  
Respiratory Metabolism ◽  
Content Type ◽  
Transport Chain ◽  
Opportunistic Fungal Pathogen ◽  
Lineage Specific Genes

ABSTRACTCandida albicansis an opportunistic fungal pathogen of major clinical concern. The virulence of this pathogen is intimately intertwined with its metabolism. Mitochondria, which have a central metabolic role, have undergone many lineage-specific adaptations in association with their eukaryotic host. A screen for lineage-specific genes identified seven such genes specific to the CTG clade of fungi, of whichC. albicansis a member. Each is required for respiratory growth and is integral to expression of complex I, III, or IV of the electron transport chain. Two genes,NUO3andNUO4, encode supernumerary subunits of complex I, whereasNUE1andNUE2have nonstructural roles in expression of complex I. Similarly, the other three genes have nonstructural roles in expression of complex III (QCE1) or complex IV (COE1andCOE2). In addition to these novel additions, an alternative functional assignment was found for the mitochondrial protein encoded byMNE1.MNE1was required for complex I expression inC. albicans, whereas the distantly relatedSaccharomyces cerevisiaeortholog participates in expression of complex III. Phenotypic analysis of deletion mutants showed that fermentative metabolism is unable to support optimal growth rates or yields ofC. albicans. However, yeast-hypha morphogenesis, an important virulence attribute, did not require respiratory metabolism under hypoxic conditions. The inability to respire also resulted in hypersensitivity to the antifungal fluconazole and in attenuated virulence in aGalleria mellonellainfection model. The results show that lineage-specific adaptations have occurred inC. albicansmitochondria and highlight the significance of respiratory metabolism in the pathobiology ofC. albicans.IMPORTANCECandida albicansis an opportunistic fungal pathogen of major clinical concern. The virulence of this pathogen is intimately intertwined with its metabolic behavior, and mitochondria have a central role in that metabolism. Mitochondria have undergone many evolutionary changes, which include lineage-specific adaptations in association with their eukaryotic host. Seven lineage-specific genes required for electron transport chain function were identified in the CTG clade of fungi, of whichC. albicansis a member. Additionally, examination of several highly diverged orthologs encoding mitochondrial proteins demonstrated functional reassignment for one of these. Deficits imparted by deletion of these genes revealed the critical role of respiration in virulence attributes of the fungus and highlight important evolutionary adaptations inC. albicansmetabolism.

scholarly journals Physiological Evidence for Isopotential Tunneling in the Electron Transport Chain of Methane-Producing Archaea

2017 ◽  
Vol 83 (18) ◽  
Author(s):  
Nikolas Duszenko ◽  
Nicole R. Buan
Keyword(s):  
Escherichia Coli ◽  
Electron Transport ◽  
Stationary Phase ◽  
Exponential Growth ◽  
Electron Transport Chain ◽  
Methanosarcina Barkeri ◽  
Metabolic Efficiency ◽  
Methanosarcina Acetivorans ◽  
Content Type ◽  
Transport Chain

ABSTRACT Many, but not all, organisms use quinones to conserve energy in their electron transport chains. Fermentative bacteria and methane-producing archaea (methanogens) do not produce quinones but have devised other ways to generate ATP. Methanophenazine (MPh) is a unique membrane electron carrier found in Methanosarcina species that plays the same role as quinones in the electron transport chain. To extend the analogy between quinones and MPh, we compared the MPh pool sizes between two well-studied Methanosarcina species, Methanosarcina acetivorans C2A and Methanosarcina barkeri Fusaro, to the quinone pool size in the bacterium Escherichia coli. We found the quantity of MPh per cell increases as cultures transition from exponential growth to stationary phase, and absolute quantities of MPh were 3-fold higher in M. acetivorans than in M. barkeri. The concentration of MPh suggests the cell membrane of M. acetivorans, but not of M. barkeri, is electrically quantized as if it were a single conductive metal sheet and near optimal for rate of electron transport. Similarly, stationary (but not exponentially growing) E. coli cells also have electrically quantized membranes on the basis of quinone content. Consistent with our hypothesis, we demonstrated that the exogenous addition of phenazine increases the growth rate of M. barkeri three times that of M. acetivorans. Our work suggests electron flux through MPh is naturally higher in M. acetivorans than in M. barkeri and that hydrogen cycling is less efficient at conserving energy than scalar proton translocation using MPh. IMPORTANCE Can we grow more from less? The ability to optimize and manipulate metabolic efficiency in cells is the difference between commercially viable and nonviable renewable technologies. Much can be learned from methane-producing archaea (methanogens) which evolved a successful metabolic lifestyle under extreme thermodynamic constraints. Methanogens use highly efficient electron transport systems and supramolecular complexes to optimize electron and carbon flow to control biomass synthesis and the production of methane. Worldwide, methanogens are used to generate renewable methane for heat, electricity, and transportation. Our observations suggest Methanosarcina acetivorans, but not Methanosarcina barkeri, has electrically quantized membranes. Escherichia coli, a model facultative anaerobe, has optimal electron transport at the stationary phase but not during exponential growth. This study also suggests the metabolic efficiency of bacteria and archaea can be improved using exogenously supplied lipophilic electron carriers. The enhancement of methanogen electron transport through methanophenazine has the potential to increase renewable methane production at an industrial scale.

scholarly journals Vibrio cholerae VciB Mediates Iron Reduction

2017 ◽  
Vol 199 (12) ◽  
Author(s):  
Eric D. Peng ◽  
Shelley M. Payne
Keyword(s):  
Electron Transport ◽  
Vibrio Cholerae ◽  
Ferrous Iron ◽  
Electron Transport Chain ◽  
Iron Reduction ◽  
Iron Transport ◽  
Ferric Iron ◽  
Transport Systems ◽  
Content Type ◽  
Transport Chain

ABSTRACT Vibrio cholerae is the causative agent of the severe diarrheal disease cholera. V. cholerae thrives within the human host, where it replicates to high numbers, but it also persists within the aquatic environments of ocean and brackish water. To survive within these nutritionally diverse environments, V. cholerae must encode the necessary tools to acquire the essential nutrient iron in all forms it may encounter. A prior study of systems involved in iron transport in V. cholerae revealed the existence of vciB, which, while unable to directly transport iron, stimulates the transport of iron through ferrous (Fe2+) iron transport systems. We demonstrate here a role for VciB in V. cholerae in which VciB stimulates the reduction of Fe3+ to Fe2+, which can be subsequently transported into the cell with the ferrous iron transporter Feo. Iron reduction is independent of functional iron transport but is associated with the electron transport chain. Comparative analysis of VciB orthologs suggests a similar role for other proteins in the VciB family. Our data indicate that VciB is a dimer located in the inner membrane with three transmembrane segments and a large periplasmic loop. Directed mutagenesis of the protein reveals two highly conserved histidine residues required for function. Taken together, our results support a model whereby VciB reduces ferric iron using energy from the electron transport chain. IMPORTANCE Vibrio cholerae is a prolific human pathogen and environmental organism. The acquisition of essential nutrients such as iron is critical for replication, and V. cholerae encodes a number of mechanisms to use iron from diverse environments. Here, we describe the V. cholerae protein VciB that increases the reduction of oxidized ferric iron (Fe3+) to the ferrous form (Fe2+), thus promoting iron acquisition through ferrous iron transporters. Analysis of VciB orthologs in Burkholderia and Aeromonas spp. suggest that they have a similar activity, allowing a functional assignment for this previously uncharacterized protein family. This study builds upon our understanding of proteins known to mediate iron reduction in bacteria.

scholarly journals Characterization of Planctomyces limnophilus and Development of Genetic Tools for Its Manipulation Establish It as a Model Species for the Phylum Planctomycetes

2011 ◽  
Vol 77 (16) ◽  
pp. 5826-5829 ◽  
Author(s):  
Christian Jogler ◽  
Frank Oliver Glöckner ◽  
Roberto Kolter
Keyword(s):  
Eukaryotic Cells ◽  
Cellular Structures ◽  
Model Species ◽  
Content Type ◽  
Genetic Tools ◽  
Carbon And Nitrogen ◽  
Nitrogen Cycles ◽  
Global Carbon ◽  
The Phylum Planctomycetes

ABSTRACTPlanctomycetesrepresent a remarkable clade in the domainBacteriabecause they play crucial roles in global carbon and nitrogen cycles and display cellular structures that closely parallel those of eukaryotic cells. Studies onPlanctomyceteshave been hampered by the lack of genetic tools, which we developed forPlanctomyces limnophilus.

scholarly journals The Complete Genome Sequence of Clostridium aceticum: a Missing Link between Rnf- and Cytochrome-Containing Autotrophic Acetogens

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Anja Poehlein ◽  
Martin Cebulla ◽  
Marcus M. Ilg ◽  
Frank R. Bengelsdorf ◽  
Bettina Schiel-Bengelsdorf ◽  
...  
Keyword(s):  
Electron Transport Chain ◽  
Proton Translocation ◽  
Acetobacterium Woodii ◽  
Content Type ◽  
Moorella Thermoacetica ◽  
Sustainable Products ◽  
Transport Chain ◽  
Acetogenic Bacteria ◽  
Biotechnological Processes ◽  
Clostridium Aceticum

ABSTRACTClostridium aceticumwas the first isolated autotrophic acetogen, converting CO2plus H2or syngas to acetate. Its genome has now been completely sequenced and consists of a 4.2-Mbp chromosome and a small circular plasmid of 5.7 kbp. Sequence analysis revealed major differences from other autotrophic acetogens.C. aceticumcontains an Rnf complex for energy conservation (via pumping protons or sodium ions). Such systems have also been found inC. ljungdahliiandAcetobacterium woodii. However,C. aceticumalso contains a cytochrome, as doesMoorella thermoacetica, which has been proposed to be involved in the generation of a proton gradient. Thus,C. aceticumseems to represent a link between Rnf- and cytochrome-containing autotrophic acetogens. InC. aceticum, however, the cytochrome is probably not involved in an electron transport chain that leads to proton translocation, as no genes for quinone biosynthesis are present in the genome.IMPORTANCEAutotrophic acetogenic bacteria are receiving more and more industrial focus, as CO2plus H2as well as syngas are interesting new substrates for biotechnological processes. They are both cheap and abundant, and their use, if it results in sustainable products, also leads to reduction of greenhouse gases.Clostridium aceticumcan use both gas mixtures, is phylogenetically not closely related to the commonly used species, and may thus become an even more attractive workhorse. In addition, its energy metabolism, which is characterized here, and the ability to synthesize cytochromes might offer new targets for improving the ATP yield by metabolic engineering and thus allow use ofC. aceticumfor production of compounds by pathways that currently present challenges for energy-limited acetogens.

scholarly journals Studies of Pseudomonas aeruginosa Mutants Indicate Pyoverdine as the Central Factor in Inhibition of Aspergillus fumigatus Biofilm

2017 ◽  
Vol 200 (1) ◽  
Author(s):  
Gabriele Sass ◽  
Hasan Nazik ◽  
John Penner ◽  
Hemi Shah ◽  
Shajia Rahman Ansari ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Aspergillus Fumigatus ◽  
Fungal Pathogens ◽  
Human Pathogens ◽  
Biofilm Growth ◽  
Content Type ◽  
Iron Deprivation

ABSTRACT Pseudomonas aeruginosa and Aspergillus fumigatus are common opportunistic bacterial and fungal pathogens, respectively. They often coexist in airways of immunocompromised patients and individuals with cystic fibrosis, where they form biofilms and cause acute and chronic illnesses. Hence, the interactions between them have long been of interest and it is known that P. aeruginosa can inhibit A. fumigatus in vitro. We have approached the definition of the inhibitory P. aeruginosa molecules by studying 24 P. aeruginosa mutants with various virulence genes deleted for the ability to inhibit A. fumigatus biofilms. The ability of P. aeruginosa cells or their extracellular products produced during planktonic or biofilm growth to affect A. fumigatus biofilm metabolism or planktonic A. fumigatus growth was studied in agar and liquid assays using conidia or hyphae. Four mutants, the pvdD pchE, pvdD, lasR rhlR, and lasR mutants, were shown to be defective in various assays. This suggested the P. aeruginosa siderophore pyoverdine as the key inhibitory molecule, although additional quorum sensing-regulated factors likely contribute to the deficiency of the latter two mutants. Studies of pure pyoverdine substantiated these conclusions and included the restoration of inhibition by the pyoverdine deletion mutants. A correlation between the concentration of pyoverdine produced and antifungal activity was also observed in clinical P. aeruginosa isolates derived from lungs of cystic fibrosis patients. The key inhibitory mechanism of pyoverdine was chelation of iron and denial of iron to A. fumigatus. IMPORTANCE Interactions between human pathogens found in the same body locale are of vast interest. These interactions could result in exacerbation or amelioration of diseases. The bacterium Pseudomonas aeruginosa affects the growth of the fungus Aspergillus fumigatus. Both pathogens form biofilms that are resistant to therapeutic drugs and host immunity. P. aeruginosa and A. fumigatus biofilms are found in vivo, e.g., in the lungs of cystic fibrosis patients. Studying 24 P. aeruginosa mutants, we identified pyoverdine as the major anti-A. fumigatus compound produced by P. aeruginosa. Pyoverdine captures iron from the environment, thus depriving A. fumigatus of a nutrient essential for its growth and metabolism. We show how microbes of different kingdoms compete for essential resources. Iron deprivation could be a therapeutic approach to the control of pathogen growth.

scholarly journals Genomic, Proteomic, and Biochemical Analysis of the Organohalide Respiratory Pathway in Desulfitobacterium dehalogenans

2014 ◽  
Vol 197 (5) ◽  
pp. 893-904 ◽  
Author(s):  
Thomas Kruse ◽  
Bram A. van de Pas ◽  
Ariane Atteia ◽  
Klaas Krab ◽  
Wilfred R. Hagen ◽  
...  
Keyword(s):  
Electron Transport ◽  
Electron Acceptor ◽  
Electron Transport Chain ◽  
Biochemical Analysis ◽  
Active Components ◽  
Organohalide Respiration ◽  
Content Type ◽  
Membrane Complex ◽  
Redox Active ◽  
Transport Chain

Desulfitobacterium dehalogenansis able to grow by organohalide respiration using 3-chloro-4-hydroxyphenyl acetate (Cl-OHPA) as an electron acceptor. We used a combination of genome sequencing, biochemical analysis of redox active components, and shotgun proteomics to study elements of the organohalide respiratory electron transport chain. The genome ofDesulfitobacterium dehalogenansJW/IU-DC1Tconsists of a single circular chromosome of 4,321,753 bp with a GC content of 44.97%. The genome contains 4,252 genes, including six rRNA operons and six predicted reductive dehalogenases. One of the reductive dehalogenases, CprA, is encoded by a well-characterizedcprTKZEBACDgene cluster. Redox active components were identified in concentrated suspensions of cells grown on formate and Cl-OHPA or formate and fumarate, using electron paramagnetic resonance (EPR), visible spectroscopy, and high-performance liquid chromatography (HPLC) analysis of membrane extracts. In cell suspensions, these components were reduced upon addition of formate and oxidized after addition of Cl-OHPA, indicating involvement in organohalide respiration. Genome analysis revealed genes that likely encode the identified components of the electron transport chain from formate to fumarate or Cl-OHPA. Data presented here suggest that the first part of the electron transport chain from formate to fumarate or Cl-OHPA is shared. Electrons are channeled from an outward-facing formate dehydrogenase via menaquinones to a fumarate reductase located at the cytoplasmic face of the membrane. When Cl-OHPA is the terminal electron acceptor, electrons are transferred from menaquinones to outward-facing CprA, via an as-yet-unidentified membrane complex, and potentially an extracellular flavoprotein acting as an electron shuttle between the quinol dehydrogenase membrane complex and CprA.

scholarly journals 5′-Methylthioadenosine Nucleosidase Is Implicated in Playing a Key Role in a Modified Futalosine Pathway for Menaquinone Biosynthesis in Campylobacter jejuni

2011 ◽  
Vol 286 (22) ◽  
pp. 19392-19398 ◽  
Author(s):  
Xu Li ◽  
Dmitry Apel ◽  
Erin C. Gaynor ◽  
Martin E. Tanner
Keyword(s):  
Campylobacter Jejuni ◽  
Electron Transport Chain ◽  
Pathogenic Bacteria ◽  
Biosynthetic Pathway ◽  
Direct Evidence ◽  
Bioinformatic Analysis ◽  
Human Pathogens ◽  
Electron Carrier ◽  
Transport Chain

Menaquinone (vitamin K2) serves as an electron carrier in the electron transport chain required for respiration in many pathogenic bacteria. Most bacteria utilize a common menaquinone biosynthetic pathway as exemplified by Escherichia coli. Recently, a novel biosynthetic pathway, the futalosine pathway, was discovered in Streptomyces. Bioinformatic analysis strongly suggests that this pathway is also operative in the human pathogens Campylobacter jejuni and Helicobacter pylori. Here, we provide compelling evidence that a modified futalosine pathway is operative in C. jejuni and that it utilizes 6-amino-6-deoxyfutalosine instead of futalosine. A key step in the Streptomyces pathway involves a nucleosidase called futalosine hydrolase. The closest homolog in C. jejuni has been annotated as a 5′-methylthioadenosine nucleosidase (MTAN). We have shown that this C. jejuni enzyme has MTAN activity but negligible futalosine hydrolase activity. However, the C. jejuni MTAN is able to hydrolyze 6-amino-6-deoxyfutalosine at a rate comparable with that of its known substrates. This suggests that the adenine-containing version of futalosine is the true biosynthetic intermediate in this organism. To demonstrate this in vivo, we constructed a C. jejuni mutant strain deleted for mqnA2, which is predicted to encode for the enzyme required to synthesize 6-amino-6-deoxyfutalosine. Growth of this mutant was readily rescued by the addition of 6-amino-6-deoxyfutalosine, but not futalosine. This provides the first direct evidence that a modified futalosine pathway is operative in C. jejuni. It also highlights the tremendous versatility of the C. jejuni MTAN, which plays key roles in S-adenosylmethionine recycling, the biosynthesis of autoinducer molecules, and the biosynthesis of menaquinone.

scholarly journals Insights into the Fundamental Physiology of the Uncultured Fe-Oxidizing BacteriumLeptothrix ochracea

2018 ◽  
Vol 84 (9) ◽  
Author(s):  
E. J. Fleming ◽  
T. Woyke ◽  
R. A. Donatello ◽  
M. M. M. Kuypers ◽  
A. Sczyrba ◽  
...  
Keyword(s):  
Electron Transport ◽  
Single Cell ◽  
Electron Transport Chain ◽  
Natural Waters ◽  
Iron Oxidation ◽  
Complex Iii ◽  
Total Carbon ◽  
Bisphosphate Carboxylase ◽  
Content Type ◽  
Transport Chain

ABSTRACTLeptothrix ochraceais known for producing large volumes of iron oxyhydroxide sheaths that alter wetland biogeochemistry. For over a century, these delicate structures have fascinated microbiologists and geoscientists. BecauseL. ochraceastill resists long-termin vitroculture, the debate regarding its metabolic classification dates back to 1885. We developed a novel culturing technique forL. ochraceausingin situnatural waters and coupled this with single-cell genomics and nanoscale secondary-ion mass spectrophotometry (nanoSIMS) to probeL. ochracea's physiology. In microslide culturesL. ochraceadoubled every 5.7 h and had an absolute growth requirement for ferrous iron, the genomic capacity for iron oxidation, and a branched electron transport chain with cytochromes putatively involved in lithotrophic iron oxidation. Additionally, its genome encoded several electron transport chain proteins, including a molybdopterin alternative complex III (ACIII), a cytochromebdoxidase reductase, and several terminal oxidase genes.L. ochraceacontained two key autotrophic proteins in the Calvin-Benson-Bassham cycle, a form II ribulose bisphosphate carboxylase, and a phosphoribulose kinase.L. ochraceaalso assimilated bicarbonate, although calculations suggest that bicarbonate assimilation is a small fraction of its total carbon assimilation. Finally,L. ochracea's fundamental physiology is a hybrid of those of the chemolithotrophicGallionella-type iron-oxidizing bacteria and the sheathed, heterotrophic filamentous metal-oxidizing bacteria of theLeptothrix-Sphaerotilusgenera. This allowsL. ochraceato inhabit a unique niche within the neutrophilic iron seeps.IMPORTANCELeptothrix ochraceawas one of three groups of organisms that Sergei Winogradsky used in the 1880s to develop his hypothesis on chemolithotrophy.L. ochraceacontinues to resist cultivation and appears to have an absolute requirement for organic-rich waters, suggesting that its true physiology remains unknown. Further,L. ochraceais an ecological engineer; a fewL. ochraceacells can generate prodigious volumes of iron oxyhydroxides, changing the ecosystem's geochemistry and ecology. Therefore, to determineL. ochracea's basic physiology, we employed new single-cell techniques to demonstrate thatL. ochraceaoxidizes iron to generate energy and, despite having predicted genes for autotrophic growth, assimilates a fraction of the total CO2that autotrophs do. Although not a true chemolithoautotroph,L. ochracea's physiological strategy allows it to be flexible and to extensively colonize iron-rich wetlands.

scholarly journals Neutralization of Mitochondrial Superoxide by Superoxide Dismutase 2 Promotes Bacterial Clearance and Regulates Phagocyte Numbers in Zebrafish

2014 ◽  
Vol 83 (1) ◽  
pp. 430-440 ◽  
Author(s):  
E. M. Peterman ◽  
C. Sullivan ◽  
M. F. Goody ◽  
I. Rodriguez-Nunez ◽  
J. A. Yoder ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Electron Transport ◽  
Mitochondrial Dysfunction ◽  
Electron Transport Chain ◽  
Bacterial Burden ◽  
Content Type ◽  
Mitochondrial Ros ◽  
Transport Chain ◽  
Severe Infections ◽  
Superoxide Dismutase 2

Mitochondria are known primarily as the location of the electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS) generated as by-products of the electron transport chain within mitochondria significantly impact cellular signaling pathways. Because of the toxic nature of ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during severe infections, mitochondrial dysfunction can occur and lead to multiorgan failure or death.Pseudomonas aeruginosais an opportunistic pathogen that can infect immunocompromised patients. Infochemicals and exotoxins associated withP. aeruginosaare capable of causing mitochondrial dysfunction. In this work, we describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish innate immune response toP. aeruginosainfection.sod2is upregulated in mammalian macrophages and neutrophils in response to lipopolysaccharidein vitro, andsod2knockdown in zebrafish results in an increased bacterial burden. Further investigation revealed that phagocyte numbers are compromised in Sod2-deficient zebrafish. Addition of the mitochondrion-targeted ROS-scavenging chemical MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2-deficient zebrafish. Our work highlights the importance of mitochondrial ROS regulation by SOD2 in the context of innate immunity and supports the use of mitochondrion-targeted ROS scavengers as potential adjuvant therapies during severe infections.

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