Valine potentiates cefoperazone-sulbactam to kill methicillin-resistant .

Unlabelled: Metabolic state-reprogramming approach was extended from Gram-negative bacteria to Gram-positive bacterium methicillin-resistant (MRSA) for identifying desired reprogramming metabolites to synergize existing antibiotic killing to MRSA. Metabolomics comparison between MRSA and methicillin-sensitive showed a depressed metabolic state in MRSA. Valine was identified as the most depressed metabolite/biomarker, and valine, leucine and isoleucine biosynthesis as the most enriched metabolic pathway.

Elevated Membrane Potential as a Tetracycline Resistance Mechanism in .

The metabolic environment is responsible for antibiotic resistance, which highlights the way in which the antibiotic resistance mechanism works. Here, GC-MS-based metabolomics with iTRAQ-based proteomics was used to characterize a metabolic state in tetracycline-resistant K12 (-R) compared with tetracycline-sensitive K12. The repressed pyruvate cycle against the elevation of the proton motive force (PMF) and ATP constructed the most characteristic feature as a consequence of tetracycline resistance.

Elevated proton motive force is a tetracycline resistance mechanism that leads to the sensitivity to gentamicin in Edwardsiella tarda.

Tetracycline is a commonly used human and veterinary antibiotic that is mostly discharged into environment and thereby tetracycline-resistant bacteria are widely isolated. To combat these resistant bacteria, further understanding for tetracycline resistance mechanisms is needed. Here, GC-MS based untargeted metabolomics with biochemistry and molecular biology techniques was used to explore tetracycline resistance mechanisms of Edwardsiella tarda.

promoter influences antibiotic resistance via proton motive force and ROS in .

Introduction: Glucose level is related to antibiotic resistance. However, underlying mechanisms are largely unknown.

Methods: Since glucose transport is performed by phosphotransferase system (PTS) in bacteria, promoter-deleted K12 (Δ-P) was used as a model to investigate effect of glucose metabolism on antibiotic resistance.

Exogenous pyruvate promotes gentamicin uptake to kill antibiotic-resistant Vibrio alginolyticus.

Objectives: Elucidating antibiotic resistance mechanisms is necessary for developing novel therapeutic strategies. The increasing incidence of antibiotic-resistant Vibrio alginolyticus infection threatens both human health and aquaculture, but the mechanism has not been fully elucidated.

Methods: Here, an isobaric tags for relative and absolute quantification (iTRAQ) functional proteomics analysis was performed on gentamicin-resistant V.

Exogenous L-Alanine promotes phagocytosis of multidrug-resistant bacterial pathogens.

Multidrug-resistant bacteria present a major threat to public health that urgently requires new drugs or treatment approaches. Here, we conduct integrated proteomic and metabolomics analyses to screen for molecular candidates improving survival of mice infected with Vibrio parahaemolyticus, which indicate that L-Alanine metabolism and phagocytosis are strongly correlated with mouse survival. We also assess the role of L-Alanine in improving mouse survival by in vivo bacterial challenge experiments using various bacteria species, including V.

Call for next-generation drugs that remove the uptake barrier to combat antibiotic resistance.

Existing antibacterial agents can be categorized into two generations, but bacterial insensitivity towards both of these generations poses a serious public health challenge worldwide. Thus, novel approaches and/or novel antibacterials are urgently needed to maintain a concentration of antibacterials that is lethal to bacteria that are resistant to existing antibiotic treatments. Metabolite(s)-based adjuvants that promote antibiotic uptake and enhance antibiotic efficacy are an effective strategy that is unlikely to develop resistance.

Fructose potentiates the protective efficiency of live cell vaccine.

Vaccination is an effective measure to prevent infection by pathogens. Live vaccines have higher protective efficacy than inactivated vaccines. However, how live vaccines interact with the host from a metabolic perspective is unknown.

Ampicillin-controlled glucose metabolism manipulates the transition from tolerance to resistance in bacteria.

The mechanism(s) of how bacteria acquire tolerance and then resistance to antibiotics remains poorly understood. Here, we show that glucose abundance decreases progressively as ampicillin-sensitive strains acquire resistance to ampicillin. The mechanism involves that ampicillin initiates this event via targeting promoter and pyruvate dehydrogenase (PDH) to promote glucose transport and inhibit glycolysis, respectively.

Glutamine potentiates gentamicin to kill lab-evolved gentamicin-resistant and clinically isolated multidrug-resistant .

Introduction: Gentamicin is a conventional antibiotic in clinic. However, with the wide use of antibiotics, gentamicin-resistant (E. coli) is an ever-increasing problem that causes infection in both humans and animals.

Poly I:C promotes malate to enhance innate immune response against bacterial infection.

Polyinosinic-polycytidylic acid (poly I:C) is a synthetic analog of double-stranded RNA (dsRNA) that activates anti-infective innate immunity. The underlying mechanisms are identified as targeting pattern recognition receptors and Th1-inducing. However, whether poly I:C manipulates metabolism to implement this anti-infective function is unknown.

Untargeted serum metabolomics reveals potential biomarkers and metabolic pathways associated with esophageal cancer.

Metabolomics has been reported as an efficient tool to screen biomarkers that are related to esophageal cancer. However, the metabolic biomarkers identifying malignant degrees and therapeutic efficacy are still largely unknown in the disease. Here, GC-MS-based metabolomics was used to understand metabolic alteration in 137 serum specimens from patients with esophageal cancer, which is approximately two- to fivefold as many plasma specimens as the previous reports.

Global transcriptional regulator FNR regulates the pyruvate cycle and proton motive force to play a role in aminoglycosides resistance of .

Bacterial metabolism is related to resistance and susceptibility to antibiotics. Fumarate and nitrate reduction regulatory protein (FNR) is a global transcriptional regulator that regulates metabolism. However, the role of FNR in antibiotic resistance is elusive.

Succinate and inosine coordinate innate immune response to bacterial infection.

Macrophages restrict bacterial infection partly by stimulating phagocytosis and partly by stimulating release of cytokines and complement components. Here, we treat macrophages with LPS and a bacterial pathogen, and demonstrate that expression of cytokine IL-1β and bacterial phagocytosis increase to a transient peak 8 to 12 h post-treatment, while expression of complement component 3 (C3) continues to rise for 24 h post-treatment. Metabolomic analysis suggests a correlation between the cellular concentrations of succinate and IL-1β and of inosine and C3.

Nitrite Promotes ROS Production to Potentiate Cefoperazone-Sulbactam-Mediated Elimination to Lab-Evolved and Clinical-Evolved Pseudomonas aeruginosa.

Cefoperazone-sulbactam (SCF)-resistant Pseudomonas aeruginosa poses a big challenge in the use of SCF to treat infection caused by the pathogen. We have recently shown exogenous nitrite-enabled killing of naturally and artificially evolved Pseudomonas aeruginosa strains (AP-R and AP-R, respectively) by SCF. However, the underlying mechanism is unknown.

A Microtitre Plate Dilution Method for Minimum Killing Concentration Is Developed to Evaluate Metabolites-Enabled Killing of Bacteria by β-lactam Antibiotics.

Because, as of yet, there are few new antibiotics active against multidrug-resistant bacteria are being explored, compounds including metabolites that might help us tide over this crisis are greatly expected. A recently adopted method to evaluate the potentiation of metabolites is the plate-counting test. However, the method is time-consuming, strenuous, and unfeasible for a large scale of screening.

Repressed Central Carbon Metabolism and Its Effect on Related Metabolic Pathways in Cefoperazone/Sulbactam-Resistant .

Metabolic shift and antibiotic resistance have been reported in . However, the global metabolic characteristics remain largely unknown. The present study characterizes the central carbon metabolism and its effect on other metabolic pathways in cefoperazone-sulbactam (SCF)-resistant (PA-R).

Activation of the TCA Cycle to Provide Immune Protection in Zebrafish Immunized by High Magnesium-Prepared Vaccine.

Vaccines are safe and efficient in controlling bacterial diseases in the aquaculture industry and are in line with green farming. The present study develops a previously unreported approach to prepare a live-attenuated vaccine by culturing bacteria in a high concentration of magnesium to attenuate bacterial virulence. Furthermore, metabolomes of zebrafish immunized with the live-attenuated vaccines were compared with those of survival and dying zebrafish infected by .

Glutamine promotes antibiotic uptake to kill multidrug-resistant uropathogenic bacteria.

The prevalence of multidrug-resistant bacteria has been increasing rapidly worldwide, a trend that poses great risk to human and animal health and creates urgent need for pharmaceutical and nonpharmaceutical approaches to stop the spread of disease due to antimicrobial resistance. Here, we found that alanine, aspartate, and glutamate metabolism was inactivated, and glutamine was repressed in multidrug-resistant uropathogenic using a comparative metabolomics approach. Exogenous glutamine promoted β-lactam–, aminoglycoside-, quinolone-, and tetracycline-induced killing of uropathogenic and potentiated ampicillin to eliminate multidrug-resistant , , , , , and .

Identification of Polyvalent Vaccine Candidates From Extracellular Secretory Proteins in .

Bacterial infections cause huge losses in aquaculture and a wide range of health issues in humans. A vaccine is the most economical, efficient, and environment-friendly agent for protecting hosts against bacterial infections. This study aimed to identify broad, cross-protective antigens from the extracellular secretory proteome of the marine bacterium .

-Inositol Restores Tilapia's Ability Against Infection by in Higher Water Temperature.

Bacterial infection presents severe challenge to tilapia farming, which is largely influenced by water temperature. However, how water temperature determines tilapias' survival to infection is not well understood. Here, we address this issue from the perspective of metabolic state.

Inactivation of Nitrite-Dependent Nitric Oxide Biosynthesis Is Responsible for Overlapped Antibiotic Resistance between Naturally and Artificially Evolved Pseudomonas aeruginosa.

Metabolic flexibility of Pseudomonas aeruginosa could lead to new strategies to combat bacterial infection. The present study used gas chromatography-mass spectrometry (GC-MS)-based metabolomics to investigate global metabolism in naturally and artificially evolved strains with cefoperazone-sulbactam (SCF) resistance (AP-R and AP-R, respectively) from the same parent strain (AP-R). Inactivation of the pyruvate cycle and nitric oxide (NO) biosynthesis was identified as characteristic features of SCF resistance in both evolved strains.

Enhanced Biosynthesis of Fatty Acids Is Associated with the Acquisition of Ciprofloxacin Resistance in Edwardsiella tarda.

Misuse and overuse of antibiotics drive the selection and spread of antibiotic-resistant bacteria. Although genetic mutations have been well defined for different types of antibiotic resistance, ways to revert antibiotic resistance are largely unexplored. Here, we adopted a proteomics approach to investigate the mechanism underlying ciprofloxacin resistance in Edwardsiella tarda, a representative pathogen that infects both economic animal species and human beings.

Synergy of alanine and gentamicin to reduce nitric oxide for elevating killing efficacy to antibiotic-resistant .

The present study explored the cooperative effect of both alanine (Ala) and gentamicin (Gent) on metabolic mechanisms by which exogenous Ala potentiates Gent to kill antibiotic-resistant . To test this, GC-MS-based metabolomics was used to characterize Ala-, Gent- and both-induced metabolic profiles, identifying nitric oxide (NO) production pathway as the most key clue to understand metabolic mechanisms. Gent, Ala and both led to low, lower and lowest activity of total nitric oxide synthase (tNOS) and level of NO, respectively.