Large-scale screening of genomic data identifies novel mobile colistin resistance genes and reveals high over-representation in Pseudomonadota
Typ
Examensarbete för masterexamen
Master's Thesis
Master's Thesis
Program
Biotechnology (MPBIO), MSc
Publicerad
2023
Författare
Schiller, Alice
Modellbyggare
Tidskriftstitel
ISSN
Volymtitel
Utgivare
Sammanfattning
The emergence of antibiotic-resistant bacteria is a health problem of great concern.
Antibiotic resistance development is driven by selection pressure and the environment is believed to be the origin of most antibiotic resistance genes, from where
they can mobilize into pathogens. In order to be prepared when novel antibiotic
resistance genes reach pathogens and prevent further transmission, early detection
and knowledge about the spread is of high importance. One specific type of antibiotic that is of high interest to characterize is colistin. Colistin is an antibiotic
that targets gram-negative bacteria and is sometimes seen as the last alternative to
treat dangerous infections caused by multi-drug resistance gram-negative bacteria.
The emergence of mobile colistin resistance genes hence threatens the efficiency of
treating these types of infections. The aim of this thesis is to identify potential novel
colistin resistance genes and evaluate them in terms of gene mobility and phylogeny.
In order to achieve this, a gene model optimized for colistin resistance genes has
been created with fARGene. This model was then used to screen large-scale bacterial genomic data for potential novel colistin resistance genes. The predicted genes
were analyzed in terms of mobility and phylogeny. This resulted in 680 257 predicted genes, over-represented in the class Gammaproteobacteria within the phylum
Pseudomonadota, that could be summarized into 1611 clusters. Out of these clusters, 104 showed signs of mobility, and many were closely related to the already
known mobile colistin resistance genes. Additionally, 13 clusters comprising potential mobile novel colistin resistance genes that are present, or at risk of ending up,
in pathogenic hosts could be identified.
Beskrivning
Ämne/nyckelord
Antibiotic resistance, colistin, profile HMM, gene mobilization, horizontal gene transfer