Efflux pumps and antimicrobial resistance: Paradoxical components in systems genomics

Kabra, Ritika; Chauhan, Nitin; Kumar, Anurag; Ingale, Prajakta; Singh, Shailza

doi:10.1016/j.pbiomolbio.2018.07.008

Cited by 40 publications

(17 citation statements)

References 108 publications

(112 reference statements)

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“…In addition, some other mechanisms of antimicrobial resistance have been reported. For instance, antimicrobials could be pumped out from bacterial cells by e ux systems [23], and the extracellular polymer substances produced by bio lms could resist antimicrobial drugs to interrupt molecular diffusion through electrostatic and steric interactions [24]. Thus, researchers discovered more antimicrobial agents to alternate traditional antibiotics when mechanisms of antimicrobial resistance were more explicit.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity Study of Chinese Medicine Madeng’ai

Tang¹,

Zhao²,

Zhang³

et al. 2021

Preprint

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Background Due to the overuse of antibiotics, many multidrug-resistant bacteria have emerged, which brings huge challenges to the clinical treatment of bacterial infections. New products for anti-infection are necessary. Methods Madeng’ai powder was added with Milli-Q water or LB culture and autoclaved to prepare medicine suspension at different concentration. Bacteria were cultured in LB with different concentration of Madeng’ai. and swab on LB agar plates to get minimal inhibitory concentration (MIC) of Madeng’ai. Mice back was cut to make wound and MRSA/PAE suspension was injected in the wound area. Then swab with Madeng’ai extracts. Bacteria growth of infected secretions was checked on LB agar, and Hematoxylin and eosin (H&E) staining was performed for Histological analysis of skin tissues infected with bacteria after Madeng’ai and PBS (control) treatment. Results Madeng’ai could widely inhibit E.faecalis, Pseudomonas aeruginosa (PAE), Klebsiella pneumoniae (K.pneumoniae) and Acinetobacter baumannii (A.baumannii) at concentration of 4.0 mg/ml. The mice model also showed that Madeng’ai had imposed restrictions on MRSA and PAE growth in vivo. Conclusion Here, we report that a new Chinese medicine Madeng’ai has antimicrobial activity functions in vitro and in vivo. These data briefly showed that Madeng’ai functioned on antimicrobial and provided a new consideration for an antibiosis product.

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Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity Study of Chinese Medicine Madeng’ai

Tang¹,

Zhao²,

Zhang³

et al. 2021

Preprint

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“…It was also identi ied that bacteria can decrease the accumulation of antibiotics by two mechanisms, namely decreasing the permeability or increasing the ef lux of antibiotics. (Kabra et al, 2019).In the case of Gram-negative bacteria, Resistance-Nodulation-Division (RND) ef lux pumps are involved in intrinsic resistance which, when activated, led to resistance to the multidrug resistance in the species like Pseudomonas aeruginosa and Enterobacteriaceae hence these are used as a novel goal which could restore susceptibility to various antibiotics. Another hypothesis suggested for the reduction of harmful outcomes of these pumps is the use of antisense peptide nucleic acids (PNAs), which are nucleic acid homologs (synthetic) where a replacement of polynucleotide phosphate sequence is observed with lexible pseudopeptide polymer.…”

Section: Agents That Inhibit Ef Lux Pumpsmentioning

confidence: 99%

A Comprehensive Review on Current Progressions in Combating The Antimicrobial Resistance

Sain¹,

Manohar²,

Gowda³

2020

ijrps

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Anti-microbial resistance (AMR) is the ability of a microbe to resist the effect of antibiotics. It has become the most important cause of concern throughout the world. AMR may develop a variety of mechanisms, including resistance, weakness or due to a certain therapeutic failure. The three major causes of resistance were identified to be over usage of anti-microbials, over-prescription, increased agricultural usage. The mechanism which leads to the development of AMR were found to be Metabolic Inactive Persister cells biofilm formation, Swarming, Obligate intracellular microbes, Reduced uptake and efflux pumps, Modification of the antibiotic binding site, Production of competitive inhibitors. Research is still being carried out and few methods successfully delay or inhibit the progress of Resistance namely: Photodynamic therapy, which works on the principle of photosensitization, results in formation of ROS which destroy pathogenic cells, Vaccines, which strengthen the defence system to fight against foreign microorganisms efficiently, Antibiotic adjuvants, work by inhibiting any kind of mechanism related to the resistance increasing the drug’s antibacterial efficiency, Nano antibiotics which acts by interfering with the mechanisms for the development of the resistance and microfluidics give a better understanding of the bacteria and its superior antimicrobial susceptibility testing. Hence, in this review the above mechanisms of antimicrobial resistance as well the latest AMR combating strategies are been discussed.

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“…Redox metabolism consists of main redox components as well as other connecting molecules like enzymes, signaling molecules, etc. To study the role and effect of other intermediates in the redox network, systems biology approaches including computational and quantitative modeling methods are nowadays being used [49]. Systems biology approaches have already been utilized to study systems dynamics of complex redox metabolic pathways in many organisms [50], such as, Escherichia coli, purple non-sulfur bacteria [51], Saccharomyces cerevisiae [52][53][54].…”

Section: Leishmaniasis and Systems-biologymentioning

confidence: 99%

Integrative Computational Framework for Understanding Metabolic Modulation in Leishmania

Chauhan

Singh

2019

Preprint

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The integration of computational and mathematical approaches is used to provide a key insight into the biological systems. Here, we seek to find detailed and more robust information on Leishmanial metabolic network by performing mathematical characterization in terms of Forman/Forman-Ricci curvature measures combined with flux balance analysis (FBA). The model prototype developed largely depends on its structure and topological components. The correlation of curvature measures with various network statistical properties revealed the structural-functional framework. The analyses helped us to identify the importance of several nodes and detect sub-networks. Our results revealed several key high curvature nodes (metabolites) belonging to common yet crucial metabolic, thus, maintaining the integrity of the network which signifies its robustness. Further analysis revealed the presence of some of these metabolites in redox metabolism of the parasite. MGO, an important node, has highly cytotoxic and mutagenic nature that can irreversibly modify DNA, proteins and enzymes, making them nonfunctional, leading to the formation of AGEs and MGO •-. Being a component in the glyoxalase pathway, we further attempted to study the outcome of the deletion of the key enzyme (GLOI) mainly involved in the neutralization of MGO by utilizing FBA. The model and the objective function both kept as simple as possible, demonstrated an interesting emergent behavior. The nonfunctional GLOI in the model contributed to 'zero' flux which signifies the key role of GLOI as a rate limiting enzyme. This has led to several fold increase production of MGO, thereby, causing an increased level of MGO •generation. Hence, the integrated computational approaches has deciphered GLOI as a potential target both from curvature measures as well as FBA which could further be explored for kinetic modeling by implying various redox-dependent constraints on the model. Designing various in vitro experimental perspectives could churn the therapeutic importance of GLOI.Leishmaniasis, one of the most neglected tropical diseases in the world, is of primary concern due to the increased risk of emerging drug resistance. To design novel drugs and search effective molecular drug targets with therapeutic importance, it is important to decipher the relation among the components responsible for leishmanial parasite survival inside the host cell at the metabolic level. Here, we have attempted to get an insight in the leishmanial metabolic network and predict the importance of key metabolites by applying mathematical characterization in terms of curvature measures and flux balance analysis (FBA). Our results identified several metabolites playing significant role in parasite's redox homeostasis. Among these MGO (methylglyoxal) caught our interest due to its highly toxic and reactive nature of irreversibly modifying DNA and proteins. FBA results helped us to look into the important role of GLOI (Glyoxalase I), the enzyme that catalyses the detoxification of MGO, in the pathway tha...

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Efflux pumps and antimicrobial resistance: Paradoxical components in systems genomics

Cited by 40 publications

References 108 publications

Antimicrobial Activity Study of Chinese Medicine Madeng’ai

Antimicrobial Activity Study of Chinese Medicine Madeng’ai

A Comprehensive Review on Current Progressions in Combating The Antimicrobial Resistance

Integrative Computational Framework for Understanding Metabolic Modulation in Leishmania

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