Metabolites in the TCA Cycle Promote Resistance to Chloramphenicol of <i>Edwardsiella tarda</i>

Wang, Chao; Dong, Xue-Sa; Yang, Yanyan; Xu, Guojing; Wu, Mengmeng; Yan, Fajun; Zhang, Longgang; An, Li; Fu, Ping; Wang, Xi-rong; Su, Yubin; Meng, Qinglei

doi:10.1021/acs.jproteome.0c00725

Cited by 15 publications

(18 citation statements)

References 47 publications

(111 reference statements)

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“…Exogenous glucose restores the sensitivity of Vibrio alginolyticus to gentamicin [48]. Metabolites in the TCA cycle promote Edwardsiella tarda resistance to chloramphenicol [49]. In this study, exogenous palmitic acid promoted the resistance of X. oryzae to ZS, whereas triclosan potentiated ZS to kill Xoo-Rzs.…”

Section: Discussionmentioning

confidence: 52%

Elevation of Fatty Acid Biosynthesis Metabolism Contributes to Zhongshengmycin Resistance in Xanthomonas oryzae

et al. 2021

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Xanthomonas oryzae severely impacts the yield and quality of rice. Antibiotics are the most common control measure for this pathogen; however, the overuse of antibiotics in past decades has caused bacterial resistance to these antibiotics. The agricultural context is of particular importance as antibiotic-resistant bacteria are prevalent, but the resistance mechanism largely remains unexplored. Herein, using gas chromatography–mass spectrometry (GC–MS), we demonstrated that zhongshengmycin-resistant X. oryzae (Xoo-Rzs) and zhongshengmycin-sensitive X. oryzae (Xoo-S) have distinct metabolic profiles. We found that the resistance to zhongshengmycin (ZS) in X. oryzae is related to increased fatty acid biosynthesis. This was demonstrated by measuring the Acetyl-CoA carboxylase (ACC) activity, the expression levels of enzyme genes involved in the fatty acid biosynthesis and degradation pathways, and adding exogenous materials, i.e., triclosan and fatty acids. Our work provides a basis for the subsequent control of the production of antibiotic-resistant strains of X. oryzae and the development of coping strategies.

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Section: Discussionmentioning

confidence: 52%

Elevation of Fatty Acid Biosynthesis Metabolism Contributes to Zhongshengmycin Resistance in Xanthomonas oryzae

et al. 2021

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“…The metabolic status of bacteria was found to play a crucial role in mediating resistance ( Zhang et al, 2019 ; Chen et al, 2022 ; Kok et al, 2022 ; Zheng et al, 2022 ). Moreover, exogenous metabolites including carbohydrates, amino acids, and nucleotides were found to modulate antibiotics susceptibility and bactericidal effects of antibacterial drugs by metabolic reprogramming in Gram-negative bacteria ( Peng et al, 2015a ; Peng et al, 2015b ; Su et al, 2015 ; Wu et al, 2015 ; Ye et al, 2018 ; Wang et al, 2020 ; Chung et al, 2022 ). Metabolites present several advantages as adjuvants for antibiotics as they are inexpensive, non-toxic, and slow to induce resistance.…”

Section: Discussionmentioning

confidence: 99%

Uracil restores susceptibility of methicillin-resistant Staphylococcus aureus to aminoglycosides through metabolic reprogramming

et al. 2023

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Background: Methicillin-resistant Staphylococcus aureus (MRSA) has now become a major nosocomial pathogen bacteria and resistant to many antibiotics. Therefore, Development of novel approaches to combat the disease is especially important. The present study aimed to provide a novel approach involving the use of nucleotide-mediated metabolic reprogramming to tackle intractable methicillin-resistant S. aureus (MRSA) infections.Objective: This study aims to explore the bacterial effects and mechanism of uracil and gentamicin in S. aureus.Methods: Antibiotic bactericidal assays was used to determine the synergistic bactericidal effect of uracil and gentamicin. How did uracil regulate bacterial metabolism including the tricarboxylic acid (TCA) cycle by GC-MS-based metabolomics. Next, genes and activity of key enzymes in the TCA cycle, PMF, and intracellular aminoglycosides were measured. Finally, bacterial respiration, reactive oxygen species (ROS), and ATP levels were also assayed in this study.Results: In the present study, we found that uracil could synergize with aminoglycosides to kill MRSA (USA300) by 400-fold. Reprogramming metabolomics displayed uracil reprogrammed bacterial metabolism, especially enhanced the TCA cycle to elevate NADH production and proton motive force, thereby promoting the uptake of antibiotics. Furthermore, uracil increased cellular respiration and ATP production, resulting the generation of ROS. Thus, the combined activity of uracil and antibiotics induced bacterial death. Inhibition of the TCA cycle or ROS production could attenuate bactericidal efficiency. Moreover, uracil exhibited bactericidal activity in cooperation with aminoglycosides against other pathogenic bacteria. In a mouse mode of MRSA infection, the combination of gentamicin and uracil increased the survival rate of infected mice.Conclusion: Our results suggest that uracil enhances the activity of bactericidal antibiotics to kill Gram-positive bacteria by modulating bacterial metabolism.

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“…Metabolites in the TCA cycle promoted resistance to chloramphenicol of E . tarda (Wang, Dong, et al, 2021). TAM, the translocation and assembly module, was found and identified as a necessary factor for pressure resistance and virulence (Li et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…For example, it was reported that Glu6P transport regulatory protein UhpA played a role in regulating the virulence gene expression (Ye et al, 2021). Metabolites in the TCA cycle promoted resistance to chloramphenicol of E. tarda (Wang, Dong, et al, 2021). TAM, the translocation and assembly module, was found and identified as a necessary factor for pressure resistance and virulence (Li et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Type II toxin–antitoxin system, RatAB, contributes to oxidative resistance, biofilm formation and virulence of Edwardsiella piscicida

Zhang

et al. 2022

Aquaculture Research

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Since the diversity and importance of its role, the type II TA system is attracting increasing attention from researchers. Edwardsiella piscicida is becoming a leading pathogen that threatens seawater and fresh aquaculture, and has been supposed to be a model organism for the study of intracellular infections. Currently, the pathogenesis of E. piscicida remains unclear, and some new pathogenic factors need to be identified. Type II TA system is largely unknown in E. piscicida. In this study, a type II TA system, RatAB, was identified and characterized in E. piscicida. RatA shares high sequence homology with RatA family toxin, and RatB shares high sequence homology with RnfH family protein. ratA and ratB form a bicistronic operon. The biological roles of RatAB were studied by mutants TX01ΔratA and TX01ΔratAB, and corresponding complementary strains. The growths of TX01ΔratA and TX01ΔratAB were similar to that of TX01 in normal LB medium. However, TX01ΔratA, especially TX01ΔratAB, were more sensitive to oxidation pressure than wild strain TX01. Two mutants' abilities to form persistent bacteria were markedly reduced compared with TX01. The deletions of ratA and ratAB reduced bacterial biofilm formation. Cell infection test indicated that the ratA and ratAB mutations damaged E. piscicida′s ability to adhere and invade host non‐phagocyte and weaken the ability of bacterial to survive and reproduce in host phagocyte. Consistently, in vivo infection tests confirmed that ratA and ratAB were required for bacterial dissemination in host tissues. Taken together, our findings demonstrate for the first time that RatAB is requisite for resistance to adversity and full virulence of E. piscicida.

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Metabolites in the TCA Cycle Promote Resistance to Chloramphenicol of Edwardsiella tarda

Cited by 15 publications

References 47 publications

Elevation of Fatty Acid Biosynthesis Metabolism Contributes to Zhongshengmycin Resistance in Xanthomonas oryzae

Elevation of Fatty Acid Biosynthesis Metabolism Contributes to Zhongshengmycin Resistance in Xanthomonas oryzae

Uracil restores susceptibility of methicillin-resistant Staphylococcus aureus to aminoglycosides through metabolic reprogramming

Type II toxin–antitoxin system, RatAB, contributes to oxidative resistance, biofilm formation and virulence of Edwardsiella piscicida

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