Variant Analysis from Bacterial Isolates Affirms DnaK Crucial for Multidrug Resistance

Mujawar, Shama; El-Aal, Amr Adel Ahmed Abd; Lahiri, Chandrajit

doi:10.1007/978-3-030-45385-5_22

Cited by 4 publications

(5 citation statements)

References 41 publications

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“…Singpanomchai et al [ 85 ] and Guitor [ 86 ] have indicated in their studies that infections that are prominent in respiratory regions cause significant rpoB gene alterations in RNA polymerase during RNA production, which is associated with rifamycin susceptibility. Mujawar et al [ 87 ] revealed that DnaK is essential for antibiotic resistance through a variety of assessments using microbial extracts. The nucleotide alterations from cytosine to adenine on DnaK gene were identified by the SNPs discovered in the individual samples that potentially caused protein denaturing [ 87 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mujawar et al [ 87 ] revealed that DnaK is essential for antibiotic resistance through a variety of assessments using microbial extracts. The nucleotide alterations from cytosine to adenine on DnaK gene were identified by the SNPs discovered in the individual samples that potentially caused protein denaturing [ 87 ]. In the same way, the DnaK-GroEL interaction may play a significant contribution to antibiotic resistance in pathogenic microorganisms [ 88 ].…”

Section: Discussionmentioning

confidence: 99%

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An integrated complete-genome sequencing and systems biology approach to predict antimicrobial resistance genes in the virulent bacterial strains of Moraxella catarrhalis

Bristy¹,

Hossain

Hasan

et al. 2023

Briefings in Functional Genomics

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Moraxella catarrhalis is a symbiotic as well as mucosal infection-causing bacterium unique to humans. Currently, it is considered as one of the leading factors of acute middle ear infection in children. As M. catarrhalis is resistant to multiple drugs, the treatment is unsuccessful; therefore, innovative and forward-thinking approaches are required to combat the problem of antimicrobial resistance (AMR). To better comprehend the numerous processes that lead to antibiotic resistance in M. catarrhalis, we have adopted a computational method in this study. From the NCBI-Genome database, we investigated 12 strains of M. catarrhalis. We explored the interaction network comprising 74 antimicrobial-resistant genes found by analyzing M. catarrhalis bacterial strains. Moreover, to elucidate the molecular mechanism of the AMR system, clustering and the functional enrichment analysis were assessed employing AMR gene interactions networks. According to the findings of our assessment, the majority of the genes in the network were involved in antibiotic inactivation; antibiotic target replacement, alteration and antibiotic efflux pump processes. They exhibit resistance to several antibiotics, such as isoniazid, ethionamide, cycloserine, fosfomycin, triclosan, etc. Additionally, rpoB, atpA, fusA, groEL and rpoL have the highest frequency of relevant interactors in the interaction network and are therefore regarded as the hub nodes. These genes can be exploited to create novel medications by serving as possible therapeutic targets. Finally, we believe that our findings could be useful to advance knowledge of the AMR system present in M. catarrhalis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

An integrated complete-genome sequencing and systems biology approach to predict antimicrobial resistance genes in the virulent bacterial strains of Moraxella catarrhalis

Bristy¹,

Hossain

Hasan

et al. 2023

Briefings in Functional Genomics

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“…It has been proposed as an attractive druggable target as well as a vaccine candidate (Fourie and Wilson, 2020). Moreover, DnaK has also been identified to be important in quorum sensing, as well as cellular integrity in bacteria by other studies (Pawar et al, 2018;Mujawar et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Again, a study on the whole-genome analysis (WGA) of protein interaction network (PIN) reported that DnaK protein was crucial in mediating quorum sensing in multidrug resistant Proteus mirabilis ( Pawar et al, 2018 ). Furthermore, WGA analyses of PIN from MDR pathogens like P. aeruginosa , S. aureus , S. enterica , S. pneumoniae , P. mirabilis , Acinetobacter baumannii , Escherichia coli , and Mycobacterium tuberculosis revealed DnaK to be among the top 10 crucial proteins indispensable for the cellular integrity of the bacteria ( Mujawar et al, 2020 ). Hence, DnaK protein has also been selected for the in silico study, herein, as a promising drug target for selected MDR bacteria.…”

Section: Discussionmentioning

confidence: 99%

Metabolite Profiling of Malaysian Gracilaria edulis Reveals Eplerenone as Novel Antibacterial Compound for Drug Repurposing Against MDR Bacteria

et al. 2021

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With a continuous threat of antimicrobial resistance on human health worldwide, efforts for new alternatives are ongoing for the management of bacterial infectious diseases. Natural products of land and sea, being conceived to be having fewer side effects, pose themselves as a welcome relief. In this respect, we have taken a scaffolded approach to unearthing the almost unexplored chemical constituents of Malaysian red seaweed, Gracilaria edulis. Essentially, a preliminary evaluation of the ethyl acetate and acetone solvent extracts, among a series of six such, revealed potential antibacterial activity against six MDR species namely, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enterica, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, and Bacillus subtilis. Detailed analyses of the inlying chemical constituents, through LC-MS and GC-MS chromatographic separation, revealed a library of metabolic compounds. These were led for further virtual screening against selected key role playing proteins in the virulence of the aforesaid bacteria. To this end, detailed predictive pharmacological analyses added up to reinforce Eplerenone as a natural alternative from the plethora of plausible bioactives. Our work adds the ongoing effort to re-discover and repurpose biochemical compounds to combat the antimicrobial resistance offered by the Gram-positive and the -negative bacterial species.

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“…Moreover, our previous work on wholegenome analysis (WGA) of protein interaction network (PIN) reported that DnaK protein was crucial in mediating quorum sensing in multidrug resistant Proteus mirabilis 69 . Furthermore, WGA analyses of PIN from MDR pathogens like P. aeruginosa, S. aureus, S. enterica, S. pneumoniae, P. mirabilis, Acinetobacter baumannii, Escherichia coli and Mycobacterium tuberculosis revealed DnaK to be among the top 10 crucial proteins indispensable for the cellular integrity of the bacteria 70 . Also, the ATP-binding pocket of DnaK chaperone has been indicated to be druggable and shown promise to cope with MDR in both gram negatives and positives (Tan & Lahiri, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Chromatographic Analyses, Virtual Screening and Pharmacokinetics of Yellow Malaysian Rambutan (Nephelium lappaceum L.) Fruit Epicarp Extracts Reveal Potential Antibacterial Compounds

Asghar¹,

Tan²,

Zahoor³

et al. 2020

Preprint

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The emergence and spread of antimicrobial resistance have been of serious concern on human health and the management of bacterial infectious diseases. Effective treatment of these diseases requires the development of novel therapeutics, preferably free of side effects. In this regard, natural products are frequently conceived to be potential alternative sources for novel antibacterial compounds. Herein, we have evaluated the antibacterial activity of the epicarp extracts of the Malaysian cultivar of yellow rambutan fruit (Nephelium lappaceum L.) against six pathogens namely, Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella enterica. Among a series of solvent extracts, fractions of ethyl acetate and acetone have revealed significant activity towards all tested strains. Chemical profiling of these fractions, via HPLC, LC-MS and GC-MS, has generated a library of potential bioactive compounds. Downstream virtual screening, pharmacological prediction, and receptor-ligand molecular dynamics simulation have eventually unveiled novel potential antibacterial compounds, which can be extracted for medicinal use. To this end, we report novel mechanistic aspects of these compounds in competitively inhibiting the ATP-binding domain of the DnaK chaperone of P. aeruginosa and MRSA. Our work takes a step forward to discover antimicrobials capable of perforating the barrier of resistance posed by both the gram positives and the negatives.

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Variant Analysis from Bacterial Isolates Affirms DnaK Crucial for Multidrug Resistance

Cited by 4 publications

References 41 publications

An integrated complete-genome sequencing and systems biology approach to predict antimicrobial resistance genes in the virulent bacterial strains of Moraxella catarrhalis

An integrated complete-genome sequencing and systems biology approach to predict antimicrobial resistance genes in the virulent bacterial strains of Moraxella catarrhalis

Metabolite Profiling of Malaysian Gracilaria edulis Reveals Eplerenone as Novel Antibacterial Compound for Drug Repurposing Against MDR Bacteria

Chromatographic Analyses, Virtual Screening and Pharmacokinetics of Yellow Malaysian Rambutan (Nephelium lappaceum L.) Fruit Epicarp Extracts Reveal Potential Antibacterial Compounds

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