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Title

Identification and prioritization of macrolideresistance genes with hypothetical annotation in Streptococcus pneumoniae

 

Authors

Blue Goad & Laura K. Harris

 

Affiliation

Davenport University, 200 S. Grand Ave, Lansing, MI, 48933, USA

 

Email

lharris86@davenport.edu

 

Article Type

Hypothesis

 

Date

Received November 21, 2018; Accepted November 22, 2018; Published December 9, 2018

 

Abstract

Macrolide resistant Streptococcus pneumoniae infections have limited treatment options. While some resistance mechanisms are well established, ample understanding is limited by incomplete genome annotation (hypothetical genes). Some hypothetical genes encode a domain of unknown function (DUF), a conserved protein domain with uncharacterized function. Here, we identify and confirm macrolide resistance genes. We further explore DUFs from macrolide resistance hypothetical genes to prioritize them for experimental characterization. We found gene similarities between two macrolide resistance gene signatures from untreated and either erythromycin- or spiramycin-treated resistant Streptococcus pneumoniae. We confirmed the association of these gene sets with macrolide resistance through comparison to gene signatures from (i) second erythromycin resistant Streptococcus pneumoniae strain, and (ii) erythromycin-treated sensitive Streptococcus pneumoniae strain, both from non-overlapping datasets. Examination into which cellular processes these macrolide resistance genes belong found connections to known resistance mechanisms such as increased amino acid biosynthesis and efflux genes, and decreased ribonucleotide biosynthesis genes, highlighting the predictive ability of the method used. 22 genes had hypothetical annotation with 10 DUFs associated with macrolide resistance. DUF characterization could uncover novel co-therapies that restore macrolide efficacy across multiple macrolide resistant species. Application of the methods to other antibiotic resistances could revolutionize treatment of resistant infections.

 

Keywords

resistance genes, hypothetical annotation, Streptococcus pneumoniae

 

Citation

Goad and Harris, Bioinformation 14(9) 488-498

 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.