Biology subjects

Bengtsson, R. J.

Publications and source records attributed to Bengtsson, R. J..

4 recordsLinked to original sources

bioRxiv2021

Informing shigellosis prevention and control through pathogen genomics

Shigella spp. are the leading bacterial cause of severe childhood diarrhoea in low- and middle-income countries (LMIC), are increasingly antimicrobial resistant and have no licensed vaccine. We performed genomic analyses of 1246 systematically collected shigellae from seven LMIC to inform control and identify factors that could limit the effectiveness of current approaches. We found that S. sonnei contributes [≥]20-fold more disease than other Shigella species relative to its genomic diversity and highlight existing diversity and adaptative capacity among S. flexneri that may generate vaccine escape variants in <6 months. Furthermore, we show convergent evolution of resistance against the current recommended antimicrobial among shigellae. This demonstrates the urgent need to integrate existing genomic diversity into vaccine and treatment plans for Shigella, and other pathogens.

microbiology↗

bioRxiv2020

Whole Genome Sequence Analysis of Shigella from Malawi Identifies Fluoroquinolone Resistance

Increasing antimicrobial resistance and limited alternative treatments led to fluoroquinolone resistant Shigella strain inclusion on the WHO global priority pathogens list. In this study we characterised multiple Shigella isolates from Malawi with whole genome sequence analysis, identifying the acquirable fluoroquinolone resistance determinant qnrS1.

genomics↗

bioRxiv2020

Global population structure and genotyping framework for genomic surveillance of the major dysentery pathogen, Shigella sonnei

Shigella sonnei is the most common agent of shigellosis in high-income countries, and causes a significant disease burden in low- and middle-income countries. Antimicrobial resistance is increasingly common in all settings. Whole genome sequencing (WGS) is increasingly utilised for S. sonnei outbreak investigation and surveillance, but comparison of data between studies and labs is challenging. Here, we present a genomic framework and genotyping scheme for S. sonnei to efficiently identify genotype and resistance determinants from WGS data. The scheme is implemented in the software package Mykrobe and tested on thousands of genomes. Applying this approach to analyse >4,000 S. sonnei isolates sequenced in public health labs in three countries identified several common genotypes associated with increased rates of ciprofloxacin resistance and azithromycin resistance, confirming intercontinental spread of highly-resistant S. sonnei clones and demonstrating the genomic framework can facilitate monitoring of the emergence and spread of resistant clones at local and global scales.

microbiology↗

bioRxiv2020

Accessory genome dynamics and structural variation of Shigella from persistent infections

Shigellosis is a diarrhoeal disease caused mainly by Shigella flexneri and Shigella sonnei. Infection from Shigella is thought to be largely self-limiting, with short- to medium- term and serotype-specific immunity provided following clearance. However, cases of men who have sex with men (MSM) associated shigellosis have been reported where Shigella of the same serotype were serially sampled from individuals between 1 to 1862 days apart, possibly due to persistent carriage or reinfection with the same serotype. Here, we investigate the accessory genome dynamics of MSM associated S. flexneri and S. sonnei isolates serially sampled from individual patients at various days apart. We find that pairs likely associated with persistent carriage infection and with smaller single nucleotide polymorphism (SNP) distance, demonstrated significantly less variation in accessory genome content than pairs likely associated with reinfection and with greater SNP-distance. We also observed evidence of antimicrobial resistance (AMR) acquisition during persistent Shigella infection, specifically the gain of extended spectrum beta-lactamase genes in two pairs associated with persistent carriage. Finally, we explored chromosomal structural variations and rearrangements in seven (5 chronic and 2 reinfection associated) pairs of S. flexneri 3a isolates from a MSM-associated epidemic sublineage, which revealed variations at several common regions across pairs. These variations were mediated by insertion sequence (IS) elements which facilitated plasticity of genetic material with a distinct predicted functional profile. This study provides insight on the variation of accessory genome dynamics and large structural genomic changes in Shigella during persistent infection. ImportanceShigella spp are Gram-negative bacteria that are the etiological agent of shigellosis, the second most common cause of diarrhoeal illness globally, particularly among children under the age of 5 in low-income countries. In high-income countries, an alternative transmission pathway of sexually transmissible disease among men who have sex with men (MSM) is emerging as the dominant presentation of the disease. Within MSM we have captured prolonged infection and/or recurrent infection with shigellae of the same serotype, challenging the belief that Shigella infection is short-lived, and confers homologous serotypic immunity. Using this recently-emerged transmission scenario we comprehensively characterise the genomic changes that occur over the course of individual infection with Shigella and uncover a distinct functional profile of variable genome regions in these globally important pathogens.

microbiology↗