Five years of GenoTyphi: updates to the global<i>Salmonella</i>Typhi genotyping framework

Dyson, Zoe A.; Holt, Kathryn E.

doi:10.1101/2021.04.28.441766

Cited by 8 publications

(5 citation statements)

References 15 publications

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“…Finally, the alignment of 17,325 SNPs from mapping of the remaining 462 isolates was utilized for phylogenetic analysis. Resultant BAM files for all isolates from RedDog mapping were used to determine previously defined genotypes according to an extended genotyping framework using the GenoTyphi pipeline 65 (available: https://github.com/katholt/genotyphi).…”

Section: Methodsmentioning

confidence: 99%

The origins of haplotype 58 (H58) Salmonella enterica serovar Typhi

Carey

Nguyen

Nhu

et al. 2022

Preprint

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Antimicrobial resistance (AMR) poses a serious threat to the clinical management of typhoid fever. AMR in Salmonella Typhi (S. Typhi) is associated with the H58 lineage, which arose comparatively recently before becoming globally disseminated. To better understand when and how this lineage emerged and became dominant, we performed detailed phylogenetic and phylodynamic analyses on contemporary genome sequences from S. Typhi isolated in the period spanning the emergence. Our dataset, which contains the earliest described H58 S. Typhi, indicates that the prototype H58 organisms were multi-drug resistant (MDR). These organisms emerged spontaneously in India in 1987 and became radially distributed throughout South Asia and then globally in the ensuing years. These early organisms were associated with a single long branch, possessing mutations associated with increased bile tolerance, suggesting that the first H58 organism was generated during chronic carriage. The subsequent use of fluoroquinolones led to several independent mutations in gyrA. The ability of H58 to acquire and maintain AMR genes continues to pose a threat, as extensively drug-resistant (XDR; MDR plus resistance to ciprofloxacin and third generation cephalosporins) variants, have emerged recently in this lineage. Understanding where and how H58 S. Typhi originated and became successful is key to understand how AMR drives successful lineages of bacterial pathogens. Additionally, these data can inform optimal targeting of typhoid conjugate vaccines (TCVs) for reducing the potential for emergence and the impact of new drug-resistant variants. Emphasis should also be placed upon the prospective identification and treatment of chronic carriers to prevent the emergence of new drug resistant variants with the ability to spread efficiently.

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Section: Methodsmentioning

confidence: 99%

The origins of haplotype 58 (H58) Salmonella enterica serovar Typhi

Carey

Nguyen

Nhu

et al. 2022

Preprint

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“…We report high rate of MDR and low-level ciprofloxacin resistant S. Typhi genotype 4.3.1.1 circulating in Zanzibar. The findings support that this clade now prevails in East Africa [16,44,50], leaving few therapeutic options available for treatment of typhoid fever in the setting. Surveillance of the prevalence, spread and antimicrobial susceptibility of S. Typhi can guide treatment and control efforts.…”

Section: Discussionmentioning

confidence: 57%

“…The only S. Typhi isolate which is not MDR belongs to genotype 4.3.1.2. This genotype has been reported in Southeast Asian countries such as India, Nepal, and Bangladesh [18], neighboring countries Kenya and Uganda [16,44,51], as well as in Tanzania [44].…”

Section: Discussionmentioning

confidence: 71%

“…Genetically S. Typhi is monomorphic [13]. A recent introduction of a phylogenetic genotyping scheme, GenoTyphi, has facilitated the interpretation of whole genome sequencing data (WGS) for S. Typhi [15][16][17]. Using this scheme, a global collection of S. Typhi isolates showed that the S. Typhi population is comprised of dozens of subclades which are specific for different geographical locations [15,17,18].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

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Predominance of multidrug-resistant Salmonella Typhi genotype 4.3.1 with low-level ciprofloxacin resistance in Zanzibar

Onken,

Moyo,

Miraji

et al. 2024

PLoS Negl Trop Dis

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Background Typhoid fever is a common cause of febrile illness in low- and middle-income countries. While multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) has spread globally, fluoroquinolone resistance has mainly affected Asia. Methods Consecutively, 1038 blood cultures were obtained from patients of all age groups with fever and/or suspicion of serious systemic infection admitted at Mnazi Mmoja Hospital, Zanzibar in 2015–2016. S. Typhi were analyzed with antimicrobial susceptibility testing and with short read (61 strains) and long read (9 strains) whole genome sequencing, including three S. Typhi strains isolated in a pilot study 2012–2013. Results Sixty-three S. Typhi isolates (98%) were MDR carrying blaTEM-1B, sul1 and sul2, dfrA7 and catA1 genes. Low-level ciprofloxacin resistance was detected in 69% (43/62), with a single gyrase mutation gyrA-D87G in 41 strains, and a single gyrA-S83F mutation in the non-MDR strain. All isolates were susceptible to ceftriaxone and azithromycin. All MDR isolates belonged to genotype 4.3.1 lineage I (4.3.1.1), with the antimicrobial resistance determinants located on a composite transposon integrated into the chromosome. Phylogenetically, the MDR subgroup with ciprofloxacin resistance clusters together with two external isolates. Conclusions We report a high rate of MDR and low-level ciprofloxacin resistant S. Typhi circulating in Zanzibar, belonging to genotype 4.3.1.1, which is widespread in Southeast Asia and African countries and associated with low-level ciprofloxacin resistance. Few therapeutic options are available for treatment of typhoid fever in the study setting. Surveillance of the prevalence, spread and antimicrobial susceptibility of S. Typhi can guide treatment and control efforts.

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“…AMR genes and point mutations were identified from sequence reads using ARIBA v2.14.4 [ 13 ] with the NCBI database [ 14 ] and the pointFinder database [ 15 ]. Genotype [ 16 ] and plasmid replicon type [ 17 ] information, as well as AMR determinants, were obtained from assemblies using Pathogenwatch [ 18 ]. Details of the methods are provided in the S upplementary materials .…”

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confidence: 99%