Rapid transcriptional responses to serum exposure are associated with sensitivity and resistance to antibody-mediated complement killing in invasive Typhimurium ST313.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsOndari, Edna M
Klemm, Elizabeth J
Msefula, Chisomo L
El Ghany, Moataz Abd
Heath, Jennifer N
Pickard, Derek J
Kingsley, Robert A
MacLennan, Calman A
MetadataShow full item record
AbstractBackground: Salmonella Typhimurium ST313 exhibits signatures of adaptation to invasive human infection, including higher resistance to humoral immune responses than gastrointestinal isolates. Full resistance to antibody-mediated complement killing (serum resistance) among nontyphoidal Salmonellae is uncommon, but selection of highly resistant strains could compromise vaccine-induced antibody immunity. Here, we address the hypothesis that serum resistance is due to a distinct genotype or transcriptome response in S. Typhimurium ST313. Methods: Six S. Typhimurium ST313 bloodstream isolates, three of which were antibody resistant, were studied. Genomic content (single nucleotide polymorphisms and larger chromosomal modifications) of the strains was determined by Illumina and PACBIO sequencing, and functionally characterized using RNA-seq, transposon directed insertion site sequencing (TraDIS), targeted gene deletion and transfer of selected point mutations in an attempt to identify features associated with serum resistance. Results: Sequence polymorphisms in genes from strains with atypical serum susceptibility when transferred from strains that were highly resistant or susceptible to a strain that exhibited intermediate susceptibility did not significantly alter serum killing phenotype. No large chromosomal modifications typified serum resistance or susceptibility. Genes required for resistance to serum identified by TraDIS and RNA-seq included those involved in exopolysaccharide synthesis, iron scavenging and metabolism. Most of the down-regulated genes were associated with membrane proteins. Resistant and susceptible strains had distinct transcriptional responses to serum, particularly related to genes responsible for polysaccharide biosynthesis. There was higher upregulation of wca locus genes, involved in the biosynthesis of colanic acid exopolysaccharide, in susceptible strains and increased expression of fepE, a regulator of very long-chain lipopolysaccharide in resistant strains. Conclusion: Clinical isolates of S. Typhimurium ST313 exhibit distinct antibody susceptibility phenotypes that may be associated with changes in gene expression on exposure to serum.
CitationWellcome Open Res. 2019 Apr 25;4:74. doi: 10.12688/wellcomeopenres.15059.1. eCollection 2019.
AffiliationHIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
JournalWellcome Open Research
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Role of <i>sapA</i> and <i>yfgA</i> in Susceptibility to Antibody-Mediated Complement-Dependent Killing and Virulence of Salmonella enterica Serovar Typhimurium.
- Authors: Ondari EM, Heath JN, Klemm EJ, Langridge G, Barquist L, Goulding DA, Clare S, Dougan G, Kingsley RA, MacLennan CA
- Issue date: 2017 Sep
- Relationship between antibody susceptibility and lipopolysaccharide O-antigen characteristics of invasive and gastrointestinal nontyphoidal Salmonellae isolates from Kenya.
- Authors: Onsare RS, Micoli F, Lanzilao L, Alfini R, Okoro CK, Muigai AW, Revathi G, Saul A, Kariuki S, MacLennan CA, Rondini S
- Issue date: 2015 Mar
- Loss of Multicellular Behavior in Epidemic African Nontyphoidal Salmonella enterica Serovar Typhimurium ST313 Strain D23580.
- Authors: Singletary LA, Karlinsey JE, Libby SJ, Mooney JP, Lokken KL, Tsolis RM, Byndloss MX, Hirao LA, Gaulke CA, Crawford RW, Dandekar S, Kingsley RA, Msefula CL, Heyderman RS, Fang FC
- Issue date: 2016 Mar 1
- Genomic analysis of human invasive Salmonella enterica serovar Typhimurium ST313 isolate B3589 from India.
- Authors: Jacob JJ, Anandan S, Venkatesan M, Neeravi A, Vasudevan K, Pragasam AK, Veeraraghavan B
- Issue date: 2019 Sep
- Invasive Salmonella Typhimurium ST313 with naturally attenuated flagellin elicits reduced inflammation and replicates within macrophages.
- Authors: Ramachandran G, Perkins DJ, Schmidlein PJ, Tulapurkar ME, Tennant SM
- Issue date: 2015 Jan