Gallbladder carriage generates genetic variation and genome degradation in Salmonella Typhi
| Autor: | To Nguyen Thi Nguyen, Maia A. Rabaa, Ho Ngoc Dan Thanh, Buddha Basnyat, Gordon Dougan, Sabina Dongol, Megan E Carey, Pham Thanh Duy, Abhilasha Karkey, Stephen Baker, Nga Tran Vu Thieu |
|---|---|
| Přispěvatelé: | Thanh Duy, Pham [0000-0001-7029-9210], Karkey, Abhilasha [0000-0002-5179-650X], Carey, Megan [0000-0002-7797-9080], Basnyat, Buddha [0000-0002-1125-2743], Rabaa, Maia A [0000-0003-0529-2228], Baker, Stephen [0000-0003-1308-5755], Apollo - University of Cambridge Repository, Rabaa, Maia A. [0000-0003-0529-2228] |
| Rok vydání: | 2020 |
| Předmět: |
Bacterial Diseases
Male Single Nucleotide Polymorphisms Adaptation Biological Pathology and Laboratory Medicine Salmonella typhi Biochemistry Medical Conditions Salmonella Genotype Typhoid Biology (General) Phylogeny Data Management 0303 health sciences education.field_of_study Vi capsular polysaccharide vaccine Computer and information sciences 030302 biochemistry & molecular biology Gallbladder Nonsense Mutation Phylogenetic Analysis Middle Aged Bacterial Pathogens 3. Good health Anti-Bacterial Agents Phylogenetics Infectious Diseases medicine.anatomical_structure Liver Medical Microbiology Female Anatomy Pathogens medicine.drug Research Article Adult QH301-705.5 Immunology Population Biology Microbiology Typhoid fever 03 medical and health sciences Enterobacteriaceae Virology DNA-binding proteins Genetic variation Genetics medicine Humans Evolutionary Systematics Genetic variability Typhoid Fever education Microbial Pathogens Molecular Biology Taxonomy 030304 developmental biology Aged Medicine and health sciences Evolutionary Biology Bacteria Biology and life sciences Whole Genome Sequencing Organisms Proteins Genetic Variation RC581-607 medicine.disease Biliary System Mutation Parasitology Immunologic diseases. Allergy |
| Zdroj: | PLoS Pathogens, Vol 16, Iss 10, p e1008998 (2020) PLoS Pathogens |
| Popis: | Despite recent advances in typhoid fever control, asymptomatic carriage of Salmonella Typhi in the gallbladder remains poorly understood. Aiming to understand if S. Typhi becomes genetically adapted for long-term colonisation in the gallbladder, we performed whole genome sequencing on a collection of S. Typhi isolated from the gallbladders of typhoid carriers. These sequences were compared to contemporaneously sampled sequences from organisms isolated from the blood of acute patients within the same population. We found that S. Typhi carriage was not restricted to any particular genotype or conformation of antimicrobial resistance genes, but was largely reflective of S. Typhi circulating in the general population. However, gallbladder isolates showed a higher genetic variability than acute isolates, with median pairwise SNP distances of 21 and 13 SNPs (p = 2.8x10-9), respectively. Within gallbladder isolates of the predominant H58 genotype, variation was associated with a higher prevalence of nonsense mutations. Notably, gallbladder isolates displayed a higher frequency of non-synonymous mutations in genes encoding hypothetical proteins, membrane lipoproteins, transport/binding proteins, surface antigens, and carbohydrate degradation. Specifically, we identified several gallbladder-specific non-synonymous mutations involved in LPS synthesis and modification, with some isolates lacking the Vi capsular polysaccharide vaccine target due to the 134Kb deletion of SPI-7. S. Typhi is under strong selective pressure in the human gallbladder, which may be reflected phylogenetically by long terminal branches that may distinguish organisms from chronic and acute infections. Our work shows that selective pressures asserted by the hostile environment of the human gallbladder generate new antigenic variants and raises questions regarding the role of carriage in the epidemiology of typhoid fever. Author summary Salmonella Typhi is the bacterium that causes typhoid. Salmonella Typhi is infamous for being able to be carried in the gallbladder, with Typhoid Mary being the best-known example of a typhoid carrier. Despite having new tools for typhoid control, we have made little progress in understanding this disease process. Aiming to understand if Salmonella Typhi is adapted for long-term survival in the gallbladder, we sequenced the genomes of 24 Salmonella Typhi isolated from the gallbladders of typhoid carriers. We compared these genomes to Salmonella Typhi from acute typhoid patients within the same population. The carriage of Salmonella Typhi was not restricted to any specific genotype or resistance to antibiotics, but reflective of the organisms causing acute disease. However, gallbladder isolates had higher genetic variability than acute isolates, with a higher frequency of mutations changing the amino acid sequences of hypothetical proteins, membrane lipoproteins, transport/binding proteins, surface antigens, and carbohydrate degradation. We identified several gallbladder-specific mutations involved in polysaccharide synthesis on the bacterial surface. Our work shows that selective pressures asserted by the hostile environment of the human gallbladder generates genetic variation, which is not observed in acute isolates, raising questions regarding the role of carriage in the epidemiology of typhoid. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|