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Uropathogenic bacteria and deductive genomics towards antimicrobial resistance, virulence, and potential drug targets

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Abstract

Urinary tract infections (UTIs) are among the most prevalent bacterial infections affecting people in inpatient and outpatient settings. The current study aimed to sequence the genome of uropathogenic Escherichia coli strain CUI-B1 resourced from a woman having uncomplicated cystitis and pyelonephritis. Followed by deductive genomics towards potential drug targets using E. coli strain CUI-B1, strain O25b: H4-ST131, Proteus mirabilis strain HI4320, Klebsiella pneumoniae strain 1721, and Staphylococcus saprophyticus strain ATCC 15305 uropathogenic strains. Comparative genome analysis revealed that genes related to the survival of E. coli, P. mirabilis, K. pneumoniae, and S. saprophyticus, such as genes of metal-requiring proteins, defense-associated genes, and genes associated with general physiology, were found to be highly conserved in the genomes including strain CUI-B1. However, the genes responsible for virulence and drug resistance, mainly those that are involved in bacterial secretion, fimbriae, adherence, and colonization, were found in various genomic regions and varied from one species to another or within the same species. Based on the genome sequence, virulence, and antimicrobial-resistant gene dataset, the subtractive proteomics approach revealed 22 proteins mapped to the pathogen’s unique pathways and among them, entB, clbH, chuV, and ybtS were supposed to be potential drug targets and the single drug could be utilized for all above-mentioned strains. These results may provide the foundation for the optimal target for future discovery of drugs for E. coli-, P. mirabilis-, K. pneumoniae-, and S. saprophyticus-based infections and could be investigated further to employ in personalized drug development.

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Data availability

The 16s RNA sequence data was submitted to GenBank/DDBJ/ENA under accession no. OQ858381, while the Whole Genome Shotgun project has been deposited at DDBJ/ENA/GenBank under the accession JARWMK000000000. The version described in this paper is version JARWMK010000000.

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Funding

This research was funded by the Researchers Supporting Project number (RSP2023R332), King Saud University, Saudi Arabia.

Author information

Authors and Affiliations

  1. Medical Department, Quaid e Azam Medical College, Bahawalpur, Pakistan

    Aaima Amin

  2. Department of Biosciences, COMSATS University Islamabad, Sahiwal Campus, Sahiwal, Pakistan

    Aaima Amin, Annam Hussain, Hafiz Muhammad Zeeshan Raza & Muhammad Ibrahim

  3. Medical Department, Fatima Jinnah Medical University, Lahore, Pakistan

    Ramisha Noureen

  4. Medical Department, Govt Khawaja Muhammad Safdar Medical Collage, Sialkot, Pakistan

    Ayesha Iftikhar

  5. Health Administration Department, College of Business Administration, King Saud University, Riyadh, 11587, Saudi Arabia

    Wadi B. Alonazi

  6. Laboratory of Genetics of Microorganisms, School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy

    Ifra Ferheen

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  1. Aaima Amin
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  4. Annam Hussain
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  8. Muhammad Ibrahim
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Contributions

AA, RN, and AI collected samples, performed basics analysis, and wrote 1st relevant 1st draft. AH, WBA, AH, and IF performed and guided bioinformatics analysis. ZMZR wrote the “Discussion” section and proof reading. MI supervised whole work and drafted the manuscript for final submission.

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Correspondence to Muhammad Ibrahim.

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Amin, A., Noureen, R., Iftikhar, A. et al. Uropathogenic bacteria and deductive genomics towards antimicrobial resistance, virulence, and potential drug targets. Int Microbiol 27, 325–335 (2024). https://doi.org/10.1007/s10123-023-00416-3

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