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Application of Comparative Biosequence Analysis to Understand Antibiotic Resistance in Superbug

Published: 04 September 2019 Publication History

Abstract

The advent of synthetic antibiotics revolutionized the treatment of bacterial infections in humans. Antibiotics are classified into several different families, depending on their mode of action, including beta-lactams, macrolides, and quinolones. Beta-lactam antibiotics work by targeting the biochemical process of building up peptidoglycan, the major component of bacterial cell walls. Macrolides work most frequently by targeting the function of bacterial ribosomes, the protein-building machine essential for the survival of bacteria. In contrast, quinolones are those for treating more aggressive forms of bacterial infections, such as pneumonia, and work by breaking the strands of replicating DNA [1]. Bacteria evolve each time they are exposed to antibiotic treatment, developing antibiotic resistance. Consequently, they disable once effective antibiotics and give rise to antibiotic crisis, the deadliest threat to human health. WHO lists 12 antibiotic-resistant bacteria as superbugs, including S. pneumoniae, H. influenzae, S. aureus, P. aeruginosa [2]. Interestingly, each of the superbugs is resistant to only one or two family of antibiotics. Very little is known about the mechanisms of antibiotic resistance, making it challenging to develop novel antibiotics that contain all the superbugs [3-4]. In particular, none of the past and current researches have clearly established phylogenetic relationships between antibiotic non-resistant and resistant bacteria. This study is focused on the A site located in the highly conserved region across all bacterial 16S rRNA sequences, one of the best documented antibiotic binding sites of aminoglycosides targeting Gram-negative bacteria [3]. The A site in the E. coli 16S rRNA secondary structure includes an internal loop of three nucleotides (A1408, A1492, and A1493), directly flanked by two basepairs C1407:G1494 and C1409:G1491. Our analysis reveals that while these positions are highly conserved positions in bacteria, a few positions in both Enterobacter and H. influenzae change from one nucleotide to another. Interestingly, both H. pylori and H. influenzae are resistant to aminoglycosides, suggesting that these observed nucleotide variations at the A site could be associated with antibiotic resistance. This study is to further examine how nucleotide variation at the A site is phylogenetically related to antibiotic resistance in the superbugs.

References

[1]
Genetic Science Learning Center. 2014. What is an antibiotic?, https://learn.genetics.utah.edu/content/microbiome/antibiotics/
[2]
World Health Organization. 2017. WHO publishes list of bacteria for which new antibiotics are urgently needed, https://www.who.int/news-room/detail/27-02--2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed
[3]
LS Gonzalez III and JP Spencer. 1998. Aminoglycosides: A practical review. American Family Physician 58, 1811--1820.
[4]
LM Weigel, DB Clewell, SR Gill, NC Clark, LK McDougal, SE Flannagan, JF Kolonay, J Shetty, GE Killgore and FC Tenover. 2003. Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus. Science 302, 1569--1571.

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  1. Application of Comparative Biosequence Analysis to Understand Antibiotic Resistance in Superbug

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        cover image ACM Conferences
        BCB '19: Proceedings of the 10th ACM International Conference on Bioinformatics, Computational Biology and Health Informatics
        September 2019
        716 pages
        ISBN:9781450366663
        DOI:10.1145/3307339
        Permission to make digital or hard copies of part or all of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for third-party components of this work must be honored. For all other uses, contact the Owner/Author.

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        Published: 04 September 2019

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        1. a site
        2. antibiotic resistance
        3. phylogenetic relationships
        4. superbugs

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