Pathogenic signature of invasive non-typhoidal <i>Salmonella</i> in Africa: implications for vaccine development

Piccini, Giulia; Montomoli, Emanuele

doi:10.1080/21645515.2020.1785791

Cited by 22 publications

(22 citation statements)

References 183 publications

(428 reference statements)

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“…In addition to AMR, the ST313 lineages have accumulated loss-of-function mutations (genome degradation) 12 . Evidence of host adaptation in ST313 involved specific pseudogenes that inactivated gene function and modified metabolic and virulence phenotypes 5 , 13 – 18 .…”

Section: Mainmentioning

confidence: 99%

Stepwise evolution of Salmonella Typhimurium ST313 causing bloodstream infection in Africa

et al. 2020

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Bloodstream infections caused by nontyphoidal Salmonella are a major public health concern in Africa, causing ~49,600 deaths every year. The most common Salmonella enterica pathovariant associated with invasive nontyphoidal Salmonella disease is Salmonella Typhimurium sequence type (ST)313. It has been proposed that antimicrobial resistance and genome degradation has contributed to the success of ST313 lineages in Africa, but the evolutionary trajectory of such changes was unclear. Here, to define the evolutionary dynamics of ST313, we sub-sampled from two comprehensive collections of Salmonella isolates from African patients with bloodstream infections, spanning 1966 to 2018. The resulting 680 genome sequences led to the discovery of a pan-susceptible ST313 lineage (ST313 L3), which emerged in Malawi in 2016 and is closely related to ST313 variants that cause gastrointestinal disease in the United Kingdom and Brazil. Genomic analysis revealed degradation events in important virulence genes in ST313 L3, which had not occurred in other ST313 lineages. Despite arising only recently in the clinic, ST313 L3 is a phylogenetic intermediate between ST313 L1 and L2, with a characteristic accessory genome. Our in-depth genotypic and phenotypic characterization identifies the crucial loss-of-function genetic events that occurred during the stepwise evolution of invasive S. Typhimurium across Africa.

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Section: Mainmentioning

confidence: 99%

Stepwise evolution of Salmonella Typhimurium ST313 causing bloodstream infection in Africa

et al. 2020

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“…The early immune response against Salmonella relies on innate immunity within the gut mucosa. In general, antibodies are necessary for resistance to systemic Salmonella infections, and as the infection progresses, an effective immune response to Salmonella relies on humoral immunity, which can provide effective protection to the host ( 20 , 21 ). A previous study reported that a novel live S .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Protective Immune Response Induced by an rfbG- Deficient Salmonella enterica Serovar Enteritidis Strain as a Live Attenuated DIVA (Differentiation of Infected and Vaccinated Animals) Vaccine in Chickens

et al. 2022

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“…This yielded a similar culture positivity-rate to other sample-types, and yielded a much wider range of STs/serovars. The fact that Salmonellae have a more diverse ecology in the household environment than previously appreciated in this setting contrasts with the narrow range of STs that cause human invasive disease [43]. The lack of overlap between the ecological niches of serovars causing colonising the household and causing human bloodstream categories is very striking.…”

Section: Discussionmentioning

confidence: 99%

Case-control investigation of invasive Salmonella disease in Malawi reveals no evidence of environmental or animal transmission of invasive strains, and supports human to human transmission

Koolman

Prakash

Diness

et al. 2022

Preprint

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Background Invasive Salmonella infections are a major cause of morbidity and mortality in Sub-Saharan Africa (SSA), but the sources and transmission routes are uncertain. We investigated potential sources for cases of invasive disease by sampling healthy people, animals, and the environment in index-case and geographically-matched control households. Methods Sixty index cases of human invasive Salmonella infection were recruited (28 invasive Non-Typhoidal Salmonella (iNTS) disease, and 32 typhoid). Each index-case household was geographically matched to a control household. Extensive microbiological sampling included stool sampling from healthy household members, stool or rectal swabs from household-associated animals and boot-sock sampling of the household environment. Results 1203 samples were taken from 120 households, yielding 43 Salmonella isolates from 25 households (overall sample positivity 3.6%). Isolates from households were all NTS and spanned 15 STs. iNTS disease was caused by 3 STs of Salmonella Typhimurium, mainly ST313. Two S. Typhimurium isolates from index cases closely matched isolates from their respective asymptomatic household members (2 and 3 SNPs different respectively). There was no overlap of STs causing iNTS disease with environmental or animal isolates, despite recovery of diverse NTS. Conclusions The finding of NTS strains from index cases matching household members, coupled with lack of overlap with either animal or environmental isolates, supports a hypothesis that healthy humans are the source of iNTS infections in the household. The breadth of NTS strains found in the household environment across all sites demonstrated the robustness of sampling and methodology to detect NTS, and suggests a diverse ecology of Salmonella in this setting. The lack of S. Typhi isolated from the household environment may suggest a need for further methodological development to culture sources of typhoid.

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Pathogenic signature of invasive non-typhoidal Salmonella in Africa: implications for vaccine development

Cited by 22 publications

References 183 publications

Stepwise evolution of Salmonella Typhimurium ST313 causing bloodstream infection in Africa

Stepwise evolution of Salmonella Typhimurium ST313 causing bloodstream infection in Africa

Evaluation of the Protective Immune Response Induced by an rfbG- Deficient Salmonella enterica Serovar Enteritidis Strain as a Live Attenuated DIVA (Differentiation of Infected and Vaccinated Animals) Vaccine in Chickens

Case-control investigation of invasive Salmonella disease in Malawi reveals no evidence of environmental or animal transmission of invasive strains, and supports human to human transmission

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