Karina Tuz

Illinois Institute of Technology

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Oscar Juárez

Illinois Institute of Technology

Pingdong Liang

Illinois Institute of Technology

Xuan Fang

Peking University

Daniel A. Raba

Michigan State University

Ming Yuan

Sixth Affiliated Hospital of Sun Yat-sen University

Russell J. Ferland

University of New England

David D. L. Minh

Illinois Institute of Technology

Yuyao Hu

Illinois Institute of Technology

Herminia Pasantes‐Morales

Universidad Nacional Autónoma de México

Rodrigo Franco

University of Nebraska–Lincoln

Cooperative Institutions

Weatherford College

180

Centre Hospitalier de Beauvais

173

Sumitomo Electric Industries (United States)

168

Illinois Institute of Technology

Universidad Nacional Autónoma de México

University of Washington

National Institutes of Health

Albany Medical Center Hospital

Seattle University

Rensselaer Polytechnic Institute

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Isovolumic Regulation in Nervous Tissue

Advances in experimental medicine and biology (2002)

O. Quesada Rodrigo Franco Karla Hernández‐Fonseca Karina Tuz

Nervous tissue

10.1007/0-306-46838-7_24

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Citations (1)

Characterization of the Pseudomonas aeruginosa NQR complex, a bacterial proton pump with roles in autopoisoning resistance

Journal of Biological Chemistry (2018)

Daniel A. Raba Mónica Rosas‐Lemus William M. Menzer Chen Li Xuan Fang

Pseudomonas aeruginosa is a Gram-negative bacterium responsible for a large number of nosocomial infections. The P. aeruginosa respiratory chain contains the ion-pumping NADH:ubiquinone oxidoreductase (NQR). This enzyme couples the transfer of electrons from NADH to ubiquinone to the pumping of sodium ions across the cell membrane, generating a gradient that drives essential cellular processes in many bacteria. In this study, we characterized P. aeruginosa NQR (Pa-NQR) to elucidate its physiologic function. Our analyses reveal that Pa-NQR, in contrast with NQR homologues from other bacterial species, is not a sodium pump, but rather a completely new form of proton pump. Homology modeling and molecular dynamics simulations suggest that cation selectivity could be determined by the exit ion channels. We also show that Pa-NQR is resistant to the inhibitor 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO). HQNO is a quinolone secreted by P. aeruginosa during infection that acts as a quorum sensing agent and also has bactericidal properties against other bacteria. Using comparative analysis and computational modeling of the ubiquinone-binding site, we identified the specific residues that confer resistance toward this inhibitor. In summary, our findings indicate that Pa-NQR is a proton pump rather than a sodium pump and is highly resistant against the P. aeruginosa–produced compound HQNO, suggesting an important role in the adaptation against autotoxicity. These results provide a deep understanding of the metabolic role of NQR in P. aeruginosa and provide insight into the structural factors that determine the functional specialization in this family of respiratory complexes. Pseudomonas aeruginosa is a Gram-negative bacterium responsible for a large number of nosocomial infections. The P. aeruginosa respiratory chain contains the ion-pumping NADH:ubiquinone oxidoreductase (NQR). This enzyme couples the transfer of electrons from NADH to ubiquinone to the pumping of sodium ions across the cell membrane, generating a gradient that drives essential cellular processes in many bacteria. In this study, we characterized P. aeruginosa NQR (Pa-NQR) to elucidate its physiologic function. Our analyses reveal that Pa-NQR, in contrast with NQR homologues from other bacterial species, is not a sodium pump, but rather a completely new form of proton pump. Homology modeling and molecular dynamics simulations suggest that cation selectivity could be determined by the exit ion channels. We also show that Pa-NQR is resistant to the inhibitor 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO). HQNO is a quinolone secreted by P. aeruginosa during infection that acts as a quorum sensing agent and also has bactericidal properties against other bacteria. Using comparative analysis and computational modeling of the ubiquinone-binding site, we identified the specific residues that confer resistance toward this inhibitor. In summary, our findings indicate that Pa-NQR is a proton pump rather than a sodium pump and is highly resistant against the P. aeruginosa–produced compound HQNO, suggesting an important role in the adaptation against autotoxicity. These results provide a deep understanding of the metabolic role of NQR in P. aeruginosa and provide insight into the structural factors that determine the functional specialization in this family of respiratory complexes.

10.1074/jbc.ra118.003194

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Citations (22)

The aerobic respiratory chain of Pseudomonas aeruginosa cultured in artificial urine media: Role of NQR and terminal oxidases

PLoS ONE (2020)

Pingdong Liang Xuan Fang Yuyao Hu Ming Yuan Daniel A. Raba

Pseudomonas aeruginosa is a Gram-negative γ-proteobacterium that forms part of the normal human microbiota and it is also an opportunistic pathogen, responsible for 30% of all nosocomial urinary tract infections. P. aeruginosa carries a highly branched respiratory chain that allows the colonization of many environments, such as the urinary tract, catheters and other medical devices. P. aeruginosa respiratory chain contains three different NADH dehydrogenases (complex I, NQR and NDH-2), whose physiologic roles have not been elucidated, and up to five terminal oxidases: three cytochrome c oxidases (COx), a cytochrome bo3 oxidase (CYO) and a cyanide-insensitive cytochrome bd-like oxidase (CIO). In this work, we studied the composition of the respiratory chain of P. aeruginosa cells cultured in Luria Broth (LB) and modified artificial urine media (mAUM), to understand the metabolic adaptations of this microorganism to the growth in urine. Our results show that the COx oxidases play major roles in mAUM, while P. aeruginosa relies on CYO when growing in LB medium. Moreover, our data demonstrate that the proton-pumping NQR complex is the main NADH dehydrogenase in both LB and mAUM. This enzyme is resistant to HQNO, an inhibitory molecule produced by P. aeruginosa, and may provide an advantage against the natural antibacterial agents produced by this organism. This work offers a clear picture of the composition of this pathogen's aerobic respiratory chain and the main roles that NQR and terminal oxidases play in urine, which is essential to understand its physiology and could be used to develop new antibiotics against this notorious multidrug-resistant microorganism.

10.1371/journal.pone.0231965

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Citations (17)

Volume Changes in Neurons: Hyperexcitability and Neuronal Death

KARGER eBooks (2006)

Herminia Pasantes‐Morales Karina Tuz

Hyponatremia propitiates and increases susceptibility to seizure episodes. In vitro, hyposmolarity induces hyperexcitability and epileptiform activity and increases the amplitude of excitatory postsynaptic potentials. Synaptic (increased glutamate vesicular release) and non-synaptic (swelling-induced extracellular space shrinkage and ephaptic interactions) might be responsible for the hyposmolarity effects on brain excitability. Neuronal volume constancy in hyponatremia is preserved by the isovolumetric regulation, relying importantly on organic osmolytes. Changes in cell volume are closely linked to neuronal death: swelling characterizes necrotic death as in acute ischemic episodes or brain trauma, whereas volume decrease is typical of apoptotic death. Swelling in necrotic death results from the intracellular Na+ increase followed by Cl- and water influx. Na+ accumulation is due initially to the Na+/K+ATPase dysfunction and subsequently from the Na+ influx through the overactivated ionotropic glutamate receptors. A second wave of swelling generates by excitotoxic derived formation of reactive oxygen species, membrane lipoperoxidation and further ion overload. Excessive swelling contributes to membrane rupture and release of cell debris, propagating the damage to adjacent cells. Apoptotic death is characterized by cell volume decrease termed apoptotic volume decrease, which in neurons seems to occur by mechanisms remarkably similar to those operating in the hyposmotic swelling-activated volume regulatory decrease, i.e. channel-mediated efflux of K+ and Cl-. A variety of K+ channels and the volume-regulated anion channel participate in apoptotic volume decrease. K+ has a protagonic role as an early element in neuronal apoptosis since a delayed rectifier K+ current IKDR is enhanced by apoptosis prior to the caspase activation, increased extracellular K+ and IKDR blockers attenuate apoptosis and intracellular K+ loss through ionophores induces apoptosis. Volume-regulated anion channel participates as well in the Cl- efflux although its role and hierarchy in the apoptotic program are not well defined. Efflux of organic osmolytes, such as taurine participate as well in apoptotic volume decrease.

Excitotoxicity

10.1159/000096326

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Citations (79)

Identification of complex III, NQR, and SDH as primary bioenergetic enzymes during the stationary phase of Pseudomonas aeruginosa cultured in urine-like conditions

Frontiers in Microbiology (2024)

Yuyao Hu Ming Yuan Alexander Thomas Julian Karina Tuz Oscar Juárez

Pseudomonas aeruginosa is a common cause of urinary tract infections by strains that are often multidrug resistant, representing a major challenge to the world’s health care system. This microorganism has a highly adaptable metabolism that allows it to colonize many environments, including the urinary tract. In this work, we have characterized the metabolic strategies used by stationary phase P. aeruginosa cells cultivated in urine-like media to understand the adaptations used by this microorganism to survive and produce disease. Our proteomics results show that cells rely on the Entner-Duodoroff pathway, pentose phosphate pathway, the Krebs cycle/ glyoxylate shunt and the aerobic oxidative phosphorylation to survive in urine-like media and other conditions. A deep characterization of the oxidative phosphorylation showed that the respiratory rate of stationary phase cells is increased 3–4 times compared to cells in the logarithmic phase of growth, indicating that the aerobic metabolism plays critical roles in the stationary phase of cells grown in urine like media. Moreover, the data show that respiratory complex III, succinate dehydrogenase and the NADH dehydrogenase NQR have important functions and could be used as targets to develop new antibiotics against this bacterium.

Metabolic pathway

Cellular respiration

10.3389/fmicb.2024.1347466

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Citations (0)

Kinetic characterization of Vibrio cholerae ApbE: Substrate specificity and regulatory mechanisms

PLoS ONE (2017)

Xuan Fang Pingdong Liang Daniel A. Raba Mónica Rosas‐Lemus Srinivas Chakravarthy

ApbE is a member of a novel family of flavin transferases that incorporates flavin mononucleotide (FMN) to subunits of diverse respiratory complexes, which fulfill important homeostatic functions. In this work a detailed characterization of Vibrio cholerae ApbE physiologic activity, substrate specificity and pH dependency was carried out. The data obtained show novel characteristics of the regulation and function of this family. For instance, our experiments indicate that divalent cations are essential for ApbE function, and that the selectivity depends largely on size and the coordination sphere of the cation. Our data also show that ApbE regulation by pH, ADP and potassium is an important mechanism that enhances the adaptation, survival and colonization of V. cholerae in the small intestine. Moreover, studies of the pH-dependency of the activity show that the reaction is favored under alkaline conditions, with a pKa of 8.4. These studies, together with sequence and structure analysis allowed us to identify His257, which is absolutely conserved in the family, as a candidate for the residue whose deprotonation controls the activity. Remarkably, the mutant H257G abolished the flavin transfer activity, strongly indicating that this residue plays an important role in the catalytic mechanism of ApbE.

Flavin mononucleotide

Divalent

Residue (chemistry)

10.1371/journal.pone.0186805

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Citations (11)

Trafficking in and to the primary cilium

Cilia (2012)

Yi-Chun Hsiao Karina Tuz Russell J. Ferland

Polarized vesicle trafficking is mediated by small GTPase proteins, such as Rabs and Arls/Arfs. These proteins have essential roles in maintaining normal cellular function, in part, through regulating intracellular trafficking. Moreover, these families of proteins have recently been implicated in the formation and function of the primary cilium. The primary cilium, which is found on almost every cell type in vertebrates, is an organelle that protrudes from the surface of the cell and functions as a signaling center. Interestingly, it has recently been linked to a variety of human diseases, collectively referred to as ciliopathies. The primary cilium has an exceptionally high density of receptors on its membrane that are important for sensing and transducing extracellular stimuli. Moreover, the primary cilium serves as a separate cellular compartment from the cytosol, providing for unique spatial and temporal regulation of signaling molecules to initiate downstream events. Thus, functional primary cilia are essential for normal signal transduction. Rabs and Arls/Arfs play critical roles in early cilia formation but are also needed for maintenance of ciliary function through their coordination with intraflagellar transport (IFT), a specialized trafficking system in primary cilia. IFT in cilia is pivotal for the proper movement of proteins into and out of this highly regulated organelle. In this review article, we explore the involvement of polarized vesicular trafficking in cilia formation and function, and discuss how defects in these processes could subsequently lead to the abnormalities observed in ciliopathies.

Ciliopathies

Intraflagellar Transport

Ciliogenesis

Organelle

Transport protein

Motile cilium

10.1186/2046-2530-1-4

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Citations (117)

[Impaired fasting glucose detection in blood donors population].

PubMed (2009)

Catarina Munguía-Miranda Reyna Gabriela Sánchez-Barrera Karina Tuz Ana Lucía Alonso-García Miguel Cruz

to identify subjects with impaired fasting glucose (IFG), from a group of apparently healthy individuals.a cross-sectional study was undertaken in 1188 blood donors, with no family history of diabetes (T2D). All these individuals were subjected to a questionnaire, and biochemical tests.the prevalence of IFG was 15.9 %, 17.1 % in men and 12.9 % in women. The average blood glucose levels in subjects with IFG were 107.2 + or - 6.5 mg/dL in men and 106.0 + or - 6.1 mg/dL in women. Sixty percent of individuals with IFG showed insulin resistance. The diagnosis of metabolic syndrome (MS) in IFG subjects was 20.2 %, according to the NCEP/ATP III criteria, 21.4 % according to the International Diabetes Federation criteria; and 29.3 % according to the American Heart Association and the National Heart, Lung and Blood Institute criteria. Seventy percent of the subjects with IFG showed hypertriglyceridemia, 51 % showed hypercholesterolemia and 85 % were over-weight or obese.the prevalence of IFG was higher than expected, comparing with other populations reported in the literature. These apparently healthy subjects were not previously diagnosed and therefore have not received preventive actions to arrest the risk of T2D.

Impaired fasting glucose

Cross-sectional study

Source

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Citations (9)

Conserved residue His-257 of Vibrio cholerae flavin transferase ApbE plays a critical role in substrate binding and catalysis

Journal of Biological Chemistry (2019)

Xuan Fang J. Osipiuk Srinivas Chakravarthy Ming Yuan William M. Menzer

Residue (chemistry)

Transferase

Ternary complex

Enzyme Catalysis

10.1074/jbc.ra119.008261

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Citations (13)

The respiratory chain of Klebsiella aerogenes in urine-like conditions: critical roles of NDH-2 and bd-terminal oxidases

Frontiers in Microbiology (2024)

Martín A. González-Montalvo Jennifer M. Sorescu Gabriella Baltes Oscar Juárez Karina Tuz

Klebsiella aerogenes is an opportunistic nosocomial bacterial pathogen that commonly causes urinary tract infections. Over the past decades, K. aerogenes strains have acquired resistance to common antibiotics that has led to the rise of multidrug-resistant and even pandrug-resistant strains. Infections produced by these strains are nearly impossible to treat, which makes K. aerogenes a global priority to develop new antibiotics and there is an urgent need to identify targets to treat infections against this pathogen. However, very little is known about the metabolism and metabolic adaptations of this bacterium in infection sites. In this work, we investigated the respiratory metabolism of K. aerogenes in conditions that resemble human urine, allowing us to identify novel targets for antibiotic development. Here we describe that, unlike other gram-negative pathogens, K. aerogenes utilizes the type-2 NADH dehydrogenase (NDH-2) as the main entry point for electrons in the respiratory chain in all growth conditions evaluated. Additionally, in urine-like media, the aerobic metabolism as a whole is upregulated, with significant increases in succinate and lactate dehydrogenase activity. Moreover, our data show that the bd -I type oxidoreductases are the main terminal oxidases of this microorganism. Our findings support an initial identification of NDH-2 and bd -I oxidase as attractive targets for the development of new drugs against K. aerogenes as they are not found in human hosts.

Enterobacter aerogenes

Alternative oxidase

10.3389/fmicb.2024.1479714

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