WGS-based screening of the co-chaperone protein DjlA-induced curved DNA binding protein A (CbpA) from a new multidrug-resistant zoonotic mastitis-causing Klebsiella pneumoniae strain: a novel molecular target of selective flavonoids

Mohammad Habibur Rahman; Salauddin Al Azad; Mohammad Fahim Uddin; Maisha Farzana; Iffat Ara Sharmeen; Kaifi Sultana Kabbo; Anika Jabin; Ashfaque Rahman; Farhan Jamil; Sanjida Ahmed Srishti; Fahmida Haque Riya; Towhid Khan; Rasel Ahmed; Nurunnahar; Samiur Rahman; Mohammad Ferdousur Rahman Khan; Md Bahanur Rahman

doi:10.1007/s11030-023-10731-6

WGS-based screening of the co-chaperone protein DjlA-induced curved DNA binding protein A (CbpA) from a new multidrug-resistant zoonotic mastitis-causing Klebsiella pneumoniae strain: a novel molecular target of selective flavonoids

Mol Divers. 2023 Oct 30. doi: 10.1007/s11030-023-10731-6. Online ahead of print.

Authors

Mohammad Habibur Rahman¹, Salauddin Al Azad^{2

3}, Mohammad Fahim Uddin^{4

3}, Maisha Farzana⁵, Iffat Ara Sharmeen⁶, Kaifi Sultana Kabbo⁷, Anika Jabin^{7

3}, Ashfaque Rahman^{7

3}, Farhan Jamil⁸, Sanjida Ahmed Srishti⁹, Fahmida Haque Riya⁹, Towhid Khan¹⁰, Rasel Ahmed¹¹, Nurunnahar¹², Samiur Rahman^{7

3}, Mohammad Ferdousur Rahman Khan¹, Md Bahanur Rahman¹³

Affiliations

¹ Molecular Microbiology and Vaccinology Lab, Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, 2202, Bangladesh.
² Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, Jiangsu, People's Republic of China.
³ Immunoinformatics and Vaccinomics Research Unit, RPG Interface Lab, Jashore, 7400, Bangladesh.
⁴ College of Material Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, Zhejiang, People's Republic of China.
⁵ School of Medicine, Dentistry and Nursing, University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK.
⁶ Department of Mathematics & Natural Sciences, School of Data Sciences, BRAC University, Dhaka, 1212, Bangladesh.
⁷ Department of Biochemistry and Microbiology, North South University, Dhaka, 1229, Bangladesh.
⁸ Department of Pharmacy, University of Asia Pacific, Farmgate, Dhaka, 1205, Bangladesh.
⁹ School of Pharmacy, BRAC University, 66 Mohakhali, Dhaka, 1212, Bangladesh.
¹⁰ Department of Medicine, Comilla Medical College, Kuchaitoli, Comilla, 3500, Bangladesh.
¹¹ School of Computing, Engineering and Digital Technologies, Teesside University, Middlesbrough, TS1 3BX, UK.
¹² Department of Mathematics, Mawlana Bhashani Science and Technology University, Tangail, 1902, Bangladesh.
¹³ Molecular Microbiology and Vaccinology Lab, Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, 2202, Bangladesh. bahanurr@bau.edu.bd.

PMID: 37902899
DOI: 10.1007/s11030-023-10731-6

Abstract

The research aimed to establish a multidrug-resistant Klebsiella pneumoniae-induced genetic model for mastitis considering the alternative mechanisms of the DjlA-mediated CbpA protein regulation. The Whole Genome Sequencing of the newly isolated K. pneumoniae strain was conducted to annotate the frequently occurring antibiotic resistance and virulence factors following PCR and MALDI-TOF mass-spectrophotometry. Co-chaperon DjlA was identified and extracted via restriction digestion on PAGE. Based on the molecular string property analysis of different DnaJ and DnaK type genes, CbpA was identified to be regulated most by the DjlA protein during mastitis. Based on the quantum tunnel-cluster profiles, CbpA was modeled as a novel target for diversified biosynthetic, and chemosynthetic compounds. Pharmacokinetic and pharmacodynamic analyses were conducted to determine the maximal point-specificity of selective flavonoids in complexing with the CbpA macromolecule at molecular docking. The molecular dynamic simulation (100 ns) of each of the flavonoid-protein complexes was studied regarding the parameters RMSD, RMSF, Rg, SASA, MMGBSA, and intramolecular hydrogen bonds; where all of them resulted significantly. To ratify all the molecular dynamic simulation outputs, the potential stability of the flavonoids in complexing with CbpA can be remarked as Quercetin > Biochanin A > Kaempherol > Myricetin, which were all significant in comparison to the control Galangin. Finally, a comprehensive drug-gene interaction pathway for each of the flavonoids was developed to determine the simultaneous and quantitative-synergistic effects of different operons belonging to the DnaJ-type proteins on the metabolism of the tested pharmacophores in CbpA. Considering all the in vitro and in silico parameters, DjlA-mediated CbpA can be a novel target for the tested flavonoids as the potential therapeutics of mastitis as futuristic drugs.

Keywords: Co-chaperone DjlA protein; DnaK Co-chaperone CbpA protein; Multidrug-resistant K. pneumoniae; Pharmacokinetics and pharmacodynamics of natural flavonoids; Whole genome sequencing.

Abstract

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