Computational assessment of phytochemicals of medicinal plants from Mexico as potential inhibitors of <i>Salmonella enterica</i> efflux pump AcrB protein

Oyedara, Omotayo Opemipo; Fadare, Olatomide A.; Franco-Frías, Eduardo; Heredia, Norma; García, Santos

doi:10.1080/07391102.2021.2024261

Cited by 6 publications

(6 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both the complexes have shown minimal deviation within 10 ns timescale. Rest of the complexes have revealed deviations in the range of 0.15–0.35 nm throughout the simulation; however, RMSD values for most of the complexes were within the acceptable range that is, below 0.3 nm (Oyedara et al, 2021; Figure 6a,b). They further reported naringenin, 5‐methoxypsoralen, and licarin as candidate inhibitors of AcrB protein.…”

Section: Resultsmentioning

confidence: 97%

In silico evaluation of phytochemicals present in Bambusa polymorpha and Citrus limon extracts against Salmonella enteric Typhimurium combined with in vitro antimicrobial and acidic stress responsive studies

Thomas

Singha

Bharadwaj

et al. 2023

Journal of Food Safety

View full text Add to dashboard Cite

Salmonella enteric serovar Typhimurium is one of the causative agents for non‐typhoidal salmonellosis which is highly associated with the consumption animal products such as eggs, pork, and poultry. Phytochemicals present in plant extracts were reported to improve food safety by inhibiting the growth of foodborne pathogens. Herein, the antimicrobial activities of Citrus limon and Bambusa polymorpha extracts were evaluated for their effectiveness in reducing the log counts of strains of S. Typhimurium inoculated in ground pork. The incorporation of undiluted extracts has resulted in 3.95 and 1.88 log reduction of S. Typhimurium, respectively with 2 h of exposure. Phytochemicals in the extracts that interfere with the activity of outer membrane (OmpA) and efflux pump regulatory proteins (MdfA, RamA) were also identified and interactions were anticipated using molecular docking and molecular dynamics simulation (MDS) studies. This study has revealed that the major phytochemicals present in the extracts were viz. phenol‐2‐ethyl, paracresol, 2, 3‐dimethoxybenzoic acid, cyclobarbital, 3‐methylsalicylhydrazide, and 3‐methoxy‐5‐methylphenol. In order to evaluate the drug likeness and toxicity, phytochemicals were screened for their physiochemical and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. ADMET studies has revealed that the screened phytochemicals with high docking scores had potent anti‐bacterial abilities and could be used in drug design studies to develop natural plant products to preferentially target the outer membrane and efflux pump regulatory proteins of S. Typhimurium, which are critically important for the survival of S. Typhimurium under stress condition.

show abstract

Section: Resultsmentioning

confidence: 97%

In silico evaluation of phytochemicals present in Bambusa polymorpha and Citrus limon extracts against Salmonella enteric Typhimurium combined with in vitro antimicrobial and acidic stress responsive studies

Thomas

Singha

Bharadwaj

et al. 2023

Journal of Food Safety

View full text Add to dashboard Cite

show abstract

Section: Mechanisms Of Inhibitionmentioning

confidence: 99%

“…Taken with permission from [83]: a [86], b [146], c [123], d [34,129], e [33], f [148], g [137], h [138], i [140], j [136], k [142], l [156], m [119], n [156], o [118], p [141], q [143], r [144], s [150], t [152], u [153], v [155], w [156], x [157]. Competitive inhibition [33] Pyranopyridine MBX3132 [131] HT within the RND transporter (T state) [34] >100 µg ml −1 [131] FQs, PIP 5ENO (MBX2319), 5ENP (MBX2931), 5ENQ (MBX3132), 5ENR (MBX3135) [34] Competitive inhibition [34] Pyridylpiperazine-based BDM88832 [148] Transmembrane domain of RND transporter (L state) [148] >500 µM >250 µM Pyridomycin 7OUK (BDM8885), 7OUL (BDM88832) [148] Allosteric inhibition [148] Antidepressant Amitriptyline [86] HT within the RND transporter (T state) [86] -CIP, NAL, norfloxacin [86] -Competitive inhibition/altered functional movements [86] Antipsychotic Chlorpromazine [86] HT within the RND transporter (T state) [86] 256 g ml −1 CIP, NAL, norfloxacin…”

Section: Mechanisms Of Inhibition Inhibition Of the Imp By Small Mole...mentioning

confidence: 99%

“… Chemical structures of selected EPIs inhibiting RND pumps in Gram-negative bacteria. Taken with permission from [ 83 ]: a [ 86 ], b [ 146 ], c [ 123 ], d [ 34, 129 ], e [ 33 ], f [ 148 ], g [ 137 ], h [ 138 ], i [ 140 ], j [ 136 ], k [ 142 ], l [ 156 ], m [ 119 ], n [ 156 ], o [ 118 ], p [ 141 ], q [ 143 ], r [ 144 ], s [ 150 ], t [ 152 ], u [ 153 ], v [ 155 ], w [ 156 ], x [ 157 ]. …”

Section: Mechanisms Of Inhibitionmentioning

confidence: 99%

“…Ohene-Agyei et al [ 119 ] identified plumbagin and nordihydroguaiaretic acid as promising EPIs of AcrAB-TolC by performing virtual screening and bioassays on a database of phytochemicals. Oyedaara et al [ 141 ] screened 71 phytochemicals found in medicinal plants for their potential as EPIs of S. enterica AcrB using molecular docking and MD simulations. Naringenin, 5-methoxypsoralen and licarin A were identified as putative EPIs based on their strong binding to the DP and HT regions of AcrB, whose stability was confirmed by MD simulations.…”

Section: Mechanisms Of Inhibitionmentioning

confidence: 99%

See 2 more Smart Citations

Tripartite efflux pumps of the RND superfamily: what did we learn from computational studies?

et al. 2023

View full text Add to dashboard Cite

Bacterial resistance to antibiotics has been long recognized as a priority to address for human health. Among all micro-organisms, the so-called multi-drug resistant (MDR) bacteria, which are resistant to most, if not all drugs in our current arsenal, are particularly worrisome. The World Health Organization has prioritized the ESKAPE ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa and Enterobacter species) pathogens, which include four Gram-negative bacterial species. In these bacteria, active extrusion of antimicrobial compounds out of the cell by means of ‘molecular guns’ known as efflux pumps is a main determinant of MDR phenotypes. The resistance-nodulation-cell division (RND) superfamily of efflux pumps connecting the inner and outer membrane in Gram-negative bacteria is crucial to the onset of MDR and virulence, as well as biofilm formation. Thus, understanding the molecular basis of the interaction of antibiotics and inhibitors with these pumps is key to the design of more effective therapeutics. With the aim to contribute to this challenge, and complement and inspire experimental research, in silico studies on RND efflux pumps have flourished in recent decades. Here, we review a selection of such investigations addressing the main determinants behind the polyspecificity of these pumps, the mechanisms of substrate recognition, transport and inhibition, as well as the relevance of their assembly for proper functioning, and the role of protein–lipid interactions. The journey will end with a perspective on the role of computer simulations in addressing the challenges posed by these beautifully complex machineries and in supporting the fight against the spread of MDR bacteria.

show abstract

Modulating the antibacterial effect of the existing antibiotics along with repurposing drug metformin

Hossain,

Rafi,

Ripa

et al. 2024

Arch Microbiol

View full text Add to dashboard Cite

Computational assessment of phytochemicals of medicinal plants from Mexico as potential inhibitors of Salmonella enterica efflux pump AcrB protein

Cited by 6 publications

References 51 publications

In silico evaluation of phytochemicals present in Bambusa polymorpha and Citrus limon extracts against Salmonella enteric Typhimurium combined with in vitro antimicrobial and acidic stress responsive studies

In silico evaluation of phytochemicals present in Bambusa polymorpha and Citrus limon extracts against Salmonella enteric Typhimurium combined with in vitro antimicrobial and acidic stress responsive studies

Tripartite efflux pumps of the RND superfamily: what did we learn from computational studies?

Modulating the antibacterial effect of the existing antibiotics along with repurposing drug metformin

Contact Info

Product

Resources

About