scholarly journals Exogenous Citrulline and Glutamine Contribute to Reverse the Resistance of Salmonella to Apramycin

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Yong ◽  
Yanhong Zhou ◽  
Kexin Liu ◽  
Guochang Liu ◽  
Liqin Wu ◽  
...  

Antibiotic resistance is an increasing concern for human and animal health worldwide. Recently, the concept of reverting bacterial resistance by changing the metabolic state of antibiotic-resistant bacteria has emerged. In this study, we investigated the reversal of Apramycin resistance in Salmonella. First, non-targeted metabonomics were used to identify key differential metabolites of drug-resistant bacteria. Then, the reversal effect of exogenous substances was verified in vivo and in vitro. Finally, the underlying mechanism was studied. The results showed that the metabolites citrulline and glutamine were significantly reduced in Apramycin-resistant Salmonella. When citrulline and glutamine were added to the culture medium of drug-resistant Salmonella, the killing effect of Apramycin was restored markedly. Mechanistic studies showed that citrulline and glutamine promoted the Tricarboxylic acid cycle, produced more NADH in the bacteria, and increased the proton-motive force, thus promoting Apramycin entry into the bacterial cells, and killing the drug-resistant bacteria. This study provides a useful method to manage infections by antibiotic-resistant bacteria.

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Jitender Yadav ◽  
Sana Ismaeel ◽  
Ayub Qadri

ABSTRACT Polymyxin B, used to treat infections caused by antibiotic-resistant Gram-negative bacteria, produces nephrotoxicity at its current dosage. We show that a combination of nonbactericidal concentration of this drug and lysophosphatidylcholine (LPC) potently inhibits growth of Salmonella and at least two other Gram-negative bacteria in vitro. This combination makes bacterial membrane porous and causes degradation of DnaK, the regulator of protein folding. Polymyxin B-LPC combination may be an effective and safer regimen against drug-resistant bacteria.


2020 ◽  
Vol 56 (92) ◽  
pp. 14353-14356
Author(s):  
Hua Ke ◽  
Fen Hu ◽  
Lingyi Meng ◽  
Qi-Hua Chen ◽  
Qian-Sheng Lai ◽  
...  

Radical-doped coordination compounds—generated as a result of lone pair–π interactions and having a long-lived charge-separated state—display photochromism and broad-spectrum antimicrobial activity, even against multi-drug-resistant bacteria.


2021 ◽  
Author(s):  
Haruko Takahashi ◽  
Gregory A. Caputo ◽  
Kenichi Kuroda

Amphiphilic antimicrobial polymers show promising potential as polymer therapeutics to fight drug resistant bacteria and biofilms.


2011 ◽  
Vol 56 (3) ◽  
pp. 1414-1417 ◽  
Author(s):  
Jien-Wei Liu ◽  
Wen-Chien Ko ◽  
Cheng-Hua Huang ◽  
Chun-Hsing Liao ◽  
Chin-Te Lu ◽  
...  

ABSTRACTThe TigecyclineIn VitroSurveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor thein vitroactivity of tigecycline against commonly encountered drug-resistant bacteria. This study compared thein vitroactivity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistantStaphylococcus aureus(MRSA;n= 759), vancomycin-resistantEnterococcus faecium(VRE;n= 191), extended-spectrum β-lactamase (ESBL)-producingEscherichia coli(n= 602), ESBL-producingKlebsiella pneumoniae(n= 736), andAcinetobacter baumannii(n= 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC90values of tigecycline against MRSA, VRE, ESBL-producingE. coli, ESBL-producingK. pneumoniae, andA. baumanniiwere 0.5, 0.125, 0.5, 2, and 8 μg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producingK. pneumoniaeand 33.8% forA. baumannii. Using the EUCAST criteria, the total error rate was also high (54.6%) forA. baumanniiisolates. The total error rates between these two methods were <5% for MRSA, VRE, and ESBL-producingE. coli. For routine susceptibility testing of ESBL-producingK. pneumoniaeandA. baumanniiagainst tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.


2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Ying Ge ◽  
Li-Wei Xu ◽  
Jian-Bin Zhen ◽  
Cheng Chen ◽  
Miao Lv ◽  
...  

Background: Infections caused by metallo-β-lactamases (MβLs)-producing antibiotic-resistant bacteria pose a severe threat to public health. The synergistic use of current antibiotics in combination with MβL inhibitors is a promising therapeutic mode against these antibiotic-resistant bacteria. Objectives: The study aimed to probe the inhibition of MβLs and obtain the active component, P1, in the degradation product after imipenem was hydrolyzed by ImiS. Methods: The hydrolysis of two carbapenems with MβL ImiS was monitored by UV-Vis in real-time, and the degradation product from the leaving group produced after imipenem was hydrolyzed (but not for faropenem) was purified by HPLC to give one component, P1. Results: Kinetic assays revealed that P1 exhibited a broad-spectrum inhibition against VIM-2, NDM-1, ImiS, and L1, from three sub-classes of MβLs, with IC50 values of 8 - 32, 13.8 - 29.3, and 14.2 - 19.2 µM, using imipenem, cefazolin, and nitrocefin as substrates, respectively. Also, P1 showed synergistic antibacterial efficacy against drug-resistant Escherichia coli producing VIM-2, NDM-1, ImiS, and L1, in combination with antibiotics, restoring 16 to 32-fold and 32 to 128-fold efficacies of imipenem and cefazolin, respectively. Spectroscopic and Ellman's reagent analyses suggested that P1, a mercaptoethyl-form imidamide, is a mechanism-based inhibitor, while faropenem has no substrate inhibition, due to the lack of a leaving group. Conclusions: This work reveals that the hydrolysate of imipenem, a carbapenem with a good leaving group, can be used in screening for broad-spectrum inhibitors of MβLs.


2020 ◽  
Vol 172 ◽  
pp. 113746
Author(s):  
Meiling Jiang ◽  
Xiaoqian Yang ◽  
Haomin Wu ◽  
Ya Huang ◽  
Jie Dou ◽  
...  

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1543 ◽  
Author(s):  
Buthaina Jubeh ◽  
Zeinab Breijyeh ◽  
Rafik Karaman

Bacterial resistance to present antibiotics is emerging at a high pace that makes the development of new treatments a must. At the same time, the development of novel antibiotics for resistant bacteria is a slow-paced process. Amid the massive need for new drug treatments to combat resistance, time and effort preserving approaches, like the prodrug approach, are most needed. Prodrugs are pharmacologically inactive entities of active drugs that undergo biotransformation before eliciting their pharmacological effects. A prodrug strategy can be used to revive drugs discarded due to a lack of appropriate pharmacokinetic and drug-like properties, or high host toxicity. A special advantage of the use of the prodrug approach in the era of bacterial resistance is targeting resistant bacteria by developing prodrugs that require bacterium-specific enzymes to release the active drug. In this article, we review the up-to-date implementation of prodrugs to develop medications that are active against drug-resistant bacteria.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mark A. T. Blaskovich ◽  
Alysha G. Elliott ◽  
Angela M. Kavanagh ◽  
Soumya Ramu ◽  
Matthew A. Cooper

Abstract Acne is a common skin affliction that involves excess sebum production and modified lipid composition, duct blockage, colonization by bacteria, and inflammation. Acne drugs target one or more of these steps, with antibiotics commonly used to treat the microbial infection for moderate to severe cases. Whilst a number of other acne therapies are purported to possess antimicrobial activity, this has been poorly documented in many cases. We conducted a comparative analysis of the activity of common topical acne drugs against the principal etiological agent associated with acne: the aerotolerant anaerobic Gram-positive organism Propionibacterium acnes (recently renamed as Cutibacterium acnes). We also assessed their impact on other bacteria that could also be affected by topical treatments, including both antibiotic-sensitive and antibiotic-resistant strains, using broth microdilution assay conditions. Drugs designated specifically as antibiotics had the greatest potency, but lost activity against resistant strains. The non-antibiotic acne agents did possess widespread antimicrobial activity, including against resistant strains, but at substantially higher concentrations. Hence, the antimicrobial activity of non-antibiotic acne agents may provide protection against a background of increased drug-resistant bacteria.


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