Team II Comparative Genomics Group

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Introduction

Background

Comparative genomics is the study of comparing genome sequences to better understand the structure and function of genes.

Fosfomycin

Fosfomycin is a natural antibacterial produced by various Streptomyces and Pseudomonas species. It is the only antibiotic currently in clinical use that targets a Mur enzyme. It is broad-spectrum bactericidal antibiotic that can be employed against both Gram-positive and Gram-negative bacteria. It interferes with cell wall synthesis, particularly inhibits the initial step involving phosphoenolpyruvate synthetase, as shown below.

Resistance of Fosfomycin involves a wide range of resistance mechanisms. Some of them include reduced uptake, target site modification, expression of antibiotic-degrading enzymes and rescue of the UDP-MurNAc biogenesis pathway (ex. mutation within MurA enzyme).

Objectives

To identify genetic determinants that could be a potential cause for Fosfomycin heteroresistance in the isolates provided.

Data

The following is the metadata of our study:

Whole Genome Approach

Phylogeny Approach

Results and Discussion

References

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Nikolaidis I, Favini-Stabile S, Dessen A. 2014. Resistance to antibiotics targeted to the bacterial cell wall. Protein Sci 23: 243–259.
Kidd, Timothy J et al. “A Klebsiella Pneumoniae Antibiotic Resistance Mechanism That Subdues Host Defences and Promotes Virulence.” EMBO Molecular Medicine 9.4 (2017): 430–447.
Guo, Qinglan et al. “Glutathione-S-Transferase FosA6 of Klebsiella Pneumoniae Origin Conferring Fosfomycin Resistance in ESBL-Producing Escherichia Coli.” Journal of Antimicrobial Chemotherapy 71.9 (2016): 2460–2465.
Gardner, Shea N., Tom Slezak, and Barry G. Hall. "kSNP3. 0: SNP detection and phylogenetic analysis of genomes without genome alignment or reference genome." Bioinformatics31.17 (2015): 2877-2878.
Shea N Gardner, Tom Slezak, Barry G. Hall; kSNP3.0: SNP detection and phylogenetic analysis of genomes without genome alignment or reference genome, Bioinformatics, Volume 31, Issue 17, 1 September 2015, Pages 2877–2878.
Kim, Mincheol, et al. "Towards a taxonomic coherence between average nucleotide identity and 16S rRNA gene sequence similarity for species demarcation of prokaryotes." International journal of systematic and evolutionary microbiology 64.2 (2014): 346-351.