Gene interaction network studies to decipher the multi-drug resistance mechanism in Salmonella enterica serovar Typhi CT18 reveal potential drug targets

Debroy, Reetika; Miryala, Sravan Kumar; Naha, Aniket; Anbarasu, Anand; Ramaiah, Sudha

doi:10.1016/j.micpath.2020.104096

Cited by 47 publications

(16 citation statements)

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“…En relación al efecto producido por el cloramfenicol registrado en la presente investigación, guarda relación con otros hallazgos donde se pudo comprobar que el 83% de aislamientos de Salmonella enterica fueron resistentes a los antibacterianos (Mateva et al, 2018). Debido a que presentan genes que confieren resistencia frente a las moléculas de polipéptido catiónico antimicrobiano (CAMP), esto se da mediante la modificación del lipopolisacárido de la membrana celular bacteriana (Debroy et al, 2020).…”

Section: Discussionunclassified

Efecto antimicrobiano de la tunta (Solanum juzepczukii) sobre la Salmonella enterica subespecie enterica serovar Typhimurium

Castro

Mamani

2021

Rev. investig. altoandin.

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The objective of the study was to investigate the antimicrobial activity of tunta on Salmonella enterica subspecies enterica serovar Typhimurium. A natural isolate of this bacterium was used that was resistant to chloramphenicol. The experiment required the preparation of a standard solution of 0,8 g / ml of tunta extract. The Kirby Bauer technique was used for the antimicrobial evaluation of the tests and the Duraffourd scale to measure the level of sensitivity. Resulting, for the ten technical repetitions of the experimental group, an average halo of 10,40 mm and a standard deviation of 0,63 of DHI (level of limit sensitivity, according to said scale). In conclusion, our work shows evidence that tunta has an antimicrobial effect at a borderline sensitivity level on Salmonella enterica subspecies enterica serovar Typhimurium. After more in-depth research, this derivative of Solanum Jueepczukii could become an alternative for the development of antibiotics of natural origin and allow a sustainable development of Andean cultures.

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Section: Discussionunclassified

Efecto antimicrobiano de la tunta (Solanum juzepczukii) sobre la Salmonella enterica subespecie enterica serovar Typhimurium

Castro

Mamani

2021

Rev. investig. altoandin.

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“…The mechanisms of antibiotic resistance are then disseminated in the environment by horizontal gene transfer (HGT) between bacteria and, for example, by lysogenic phages [ 13 , 14 ]. The primary and common mechanism of bacterial resistance to antimicrobial agents is multidrug efflux systems [ 15 , 16 ]. The efflux systems can transport a wide variety of structurally diverse antimicrobial agents and some metabolites out of the bacterial cell.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Regulation of the Multiple Resistance Mechanisms in Salmonella—A Review

et al. 2021

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The widespread use of antibiotics, especially those with a broad spectrum of activity, has resulted in the development of multidrug resistance in many strains of bacteria, including Salmonella. Salmonella is among the most prevalent causes of intoxication due to the consumption of contaminated food and water. Salmonellosis caused by this pathogen is pharmacologically treated using antibiotics such as fluoroquinolones, ceftriaxone, and azithromycin. This foodborne pathogen developed several molecular mechanisms of resistance both on the level of global and local transcription modulators. The increasing rate of antibiotic resistance in Salmonella poses a significant global concern, and an improved understanding of the multidrug resistance mechanisms in Salmonella is essential for choosing the suitable antibiotic for the treatment of infections. In this review, we summarized the current knowledge of molecular mechanisms that control gene expression related to antibiotic resistance of Salmonella strains. We characterized regulators acting as transcription activators and repressors, as well as two-component signal transduction systems. We also discuss the background of the molecular mechanisms of the resistance to metals, regulators of multidrug resistance to antibiotics, global regulators of the LysR family, as well as regulators of histone-like proteins.

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“…Recent studies demonstrated the potential antibacterial activity of the novel SUL-DUR (βL-βLI) inhibitor combination which is currently under phase-III clinical trials and might be helpful in treating infections caused by A. baumannii [McLeod et al, 2020;Yahav et al, 2020]. Our research group has worked extensively to understand the protein-ligand interaction and complex AMR mechanisms of pathogenic bacteria through genomic analyses [Jacob et al, 2019;Vasudevan et al, 2020;Vijayakumar et al, 2016Vijayakumar et al, , 2020, in-silico structural [Basu et al, 2020[Basu et al, , 2021Lavanya et al, 2015;Thillainayagam et al, 2020], and systems biology approaches [Debroy et al, 2020;Miryala et al, 2020Miryala et al, , 2021Naha et al, 2020]. The aim of the present study was to decipher the activity of this βL-βLI combination against A. baumannii by characterising the inter-molecular binding profiles of SUL with PBP3 and the potency of DUR to restore the efficacy of SUL by inhibiting the β-lactamases and PBP2 through in-silico and in-vitro analyses.…”

Section: Introductionmentioning

confidence: 99%

Genome sequencing and molecular characterisation of XDR Acinetobacter baumannii reveal complexities in resistance: Novel combination of Sulbactam-Durlobactam holds promise for therapeutic intervention

Naha

Vijayakumar

Lal

et al. 2021

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Acinetobacter baumannii is an emerging nosocomial strain expressing extensive drug resistance (XDR). Whole-genome sequencing and molecular characterisation analysis revealed the presence of carbapenemase in 92.86% of studied Indian isolates having blaOXA-51, blaOXA-23, blaOXA-58, and blaNDM genes, with a few evidences of dual carbapenemase genes. As per the MLST scheme, IC2Oxf/CC2Pas was the predominant clone, with 57.14% isolates belonging to this lineage. The presence of β-lactamases has rendered sulbactam (SUL) resistance (MIC: 16-256µg/ml) in all the studied isolates. The efficacy of novel durlobactam (DUR) in inhibiting β-lactamases and PBP2 was assessed through in-silico inter-molecular interaction analysis. Several non-synonymous single nucleotide polymorphisms (nsSNPs) were identified in PBP2 (G264S, I108V, S259T) and PBP3 (A515V, T526S) sequences. Minimal variations were recorded in the protein-backbone dynamics in active-site motifs of wild-type (WT) and mutants (MT), which correlated with the negligible binding energy fluctuations for PBP3-SUL (−5.85±0.04Kcal/mol) and PBP2-DUR (−5.16±0.66Kcal/mol) complexes. Furthermore, stronger binding affinities and low inhibition constants were noted in DUR complexed with OXA23 (−7.36Kcal/mol; 4.01µM), OXA58 (−6.44Kcal/mol; 19.07µM) and NDM (−6.82Kcal/mol; 10.01µM) when compared with conventional drugs avibactam and aztreonam. Stable interaction profiles of DUR, can possibly restore SUL activity against both PBP3WT and PBP3MTs. The study establishes the efficacy of novel SUL-DUR combination as a successful treatment strategy to combat emerging XDR strains.

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Gene interaction network studies to decipher the multi-drug resistance mechanism in Salmonella enterica serovar Typhi CT18 reveal potential drug targets

Cited by 47 publications

References 47 publications

Efecto antimicrobiano de la tunta (Solanum juzepczukii) sobre la Salmonella enterica subespecie enterica serovar Typhimurium

Efecto antimicrobiano de la tunta (Solanum juzepczukii) sobre la Salmonella enterica subespecie enterica serovar Typhimurium

Transcriptional Regulation of the Multiple Resistance Mechanisms in Salmonella—A Review

Genome sequencing and molecular characterisation of XDR Acinetobacter baumannii reveal complexities in resistance: Novel combination of Sulbactam-Durlobactam holds promise for therapeutic intervention

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