Whole genome sequencing analysis to evaluate the influence of T2DM on polymorphisms associated with drug resistance in M. tuberculosis.
Antitubercular Agents
/ pharmacology
Diabetes Mellitus, Type 2
/ drug therapy
Drug Resistance, Multiple, Bacterial
/ genetics
Humans
Microbial Sensitivity Tests
Mycobacterium tuberculosis
Phylogeny
Polymorphism, Single Nucleotide
Rifampin
/ therapeutic use
Tuberculosis
/ drug therapy
Tuberculosis, Multidrug-Resistant
/ drug therapy
Whole Genome Sequencing
Diabetes
Drug resistance
Polymorphisms
Tuberculosis
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
24 Jun 2022
24 Jun 2022
Historique:
received:
14
03
2022
accepted:
16
06
2022
entrez:
24
6
2022
pubmed:
25
6
2022
medline:
29
6
2022
Statut:
epublish
Résumé
Type 2 diabetes mellitus (T2DM) has been associated with treatment failure, and the development of drug resistance in tuberculosis (TB). Also, whole-genome sequencing has provided a better understanding and allowed the growth of knowledge about polymorphisms in genes associated with drug resistance. Considering the above, this study analyzes genome sequences to evaluate the influence of type 2 diabetes mellitus in the development of mutations related to tuberculosis drug resistance. M. tuberculosis isolates from individuals with (n = 74), and without (n = 74) type 2 diabetes mellitus was recovered from online repositories, and further analyzed. The results showed the presence of 431 SNPs with similar proportions between diabetics, and non-diabetics individuals (48% vs. 52%), but with no significant relationship. A greater number of mutations associated with rifampicin resistance was observed in the T2DM-TB individuals (23.2% vs. 16%), and the exclusive presence of rpoBQ432L, rpoBQ432P, rpoBS441L, and rpoBH445L variants. While these variants are not private to T2DM-TB cases they are globally rare highlighting a potential role of T2DM. The phylogenetic analysis showed 12 sublineages, being 4.1.1.3, and 4.1.2.1 the most prevalent in T2DM-TB individuals but not differing from those most prevalent in their geographic location. Four clonal complexes were found, however, no significant relationship with T2DM was observed. Samples size and potential sampling biases prevented us to look for significant associations. The occurrence of globally rare rifampicin variants identified only in isolates from individuals with T2DM could be due to the hyperglycemic environment within the host. Therefore, further studies about the dynamics of SNPs' generation associated with antibiotic resistance in patients with diabetes mellitus are necessary.
Sections du résumé
BACKGROUND
BACKGROUND
Type 2 diabetes mellitus (T2DM) has been associated with treatment failure, and the development of drug resistance in tuberculosis (TB). Also, whole-genome sequencing has provided a better understanding and allowed the growth of knowledge about polymorphisms in genes associated with drug resistance. Considering the above, this study analyzes genome sequences to evaluate the influence of type 2 diabetes mellitus in the development of mutations related to tuberculosis drug resistance. M. tuberculosis isolates from individuals with (n = 74), and without (n = 74) type 2 diabetes mellitus was recovered from online repositories, and further analyzed.
RESULTS
RESULTS
The results showed the presence of 431 SNPs with similar proportions between diabetics, and non-diabetics individuals (48% vs. 52%), but with no significant relationship. A greater number of mutations associated with rifampicin resistance was observed in the T2DM-TB individuals (23.2% vs. 16%), and the exclusive presence of rpoBQ432L, rpoBQ432P, rpoBS441L, and rpoBH445L variants. While these variants are not private to T2DM-TB cases they are globally rare highlighting a potential role of T2DM. The phylogenetic analysis showed 12 sublineages, being 4.1.1.3, and 4.1.2.1 the most prevalent in T2DM-TB individuals but not differing from those most prevalent in their geographic location. Four clonal complexes were found, however, no significant relationship with T2DM was observed. Samples size and potential sampling biases prevented us to look for significant associations.
CONCLUSIONS
CONCLUSIONS
The occurrence of globally rare rifampicin variants identified only in isolates from individuals with T2DM could be due to the hyperglycemic environment within the host. Therefore, further studies about the dynamics of SNPs' generation associated with antibiotic resistance in patients with diabetes mellitus are necessary.
Identifiants
pubmed: 35751020
doi: 10.1186/s12864-022-08709-z
pii: 10.1186/s12864-022-08709-z
pmc: PMC9229755
doi:
Substances chimiques
Antitubercular Agents
0
Rifampin
VJT6J7R4TR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
465Subventions
Organisme : Consejo Nacional de Ciencia y Tecnología
ID : 710466
Organisme : Consejo Nacional de Ciencia y Tecnología
ID : A1-S-22956
Informations de copyright
© 2022. The Author(s).
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