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Relationship between antibody susceptibility and lipopolysaccharide O-antigen characteristics of invasive and gastrointestinal nontyphoidal Salmonellae isolates from Kenya.

Onsare RS, Micoli F, Lanzilao L, Alfini R, Okoro CK, Muigai AW, Revathi G, Saul A, Kariuki S, MacLennan CA, Rondini S - PLoS Negl Trop Dis (2015)

Bottom Line: Typhimurium, but not Enteritidis, O-antigen expression correlated with reduced sensitivity to killing (r = 0.29, 95% CI = 0.10-0.45, p = 0.002).Typhimurium.Genome studies are required to understand whether invasive and gastrointestinal isolates differ at the genotypic level.

View Article: PubMed Central - PubMed

Affiliation: Centre for Microbiology Research (CMR), Kenya Medical Research Institute (KEMRI), Nairobi, Kenya; Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya.

ABSTRACT

Background: Nontyphoidal Salmonellae (NTS) cause a large burden of invasive and gastrointestinal disease among young children in sub-Saharan Africa. No vaccine is currently available. Previous reports indicate the importance of the O-antigen of Salmonella lipopolysaccharide for virulence and resistance to antibody-mediated killing. We hypothesised that isolates with more O-antigen have increased resistance to antibody-mediated killing and are more likely to be invasive than gastrointestinal.

Methodology/principal findings: We studied 192 NTS isolates (114 Typhimurium, 78 Enteritidis) from blood and stools, mostly from paediatric admissions in Kenya 2000-2011. Isolates were tested for susceptibility to antibody-mediated killing, using whole adult serum. O-antigen structural characteristics, including O-acetylation and glucosylation, were investigated. Overall, isolates were susceptible to antibody-mediated killing, but S. Enteritidis were less susceptible and expressed more O-antigen than Typhimurium (p<0.0001 for both comparisons). For S. Typhimurium, but not Enteritidis, O-antigen expression correlated with reduced sensitivity to killing (r = 0.29, 95% CI = 0.10-0.45, p = 0.002). Both serovars expressed O-antigen populations ranging 21-33 kDa average molecular weight. O-antigen from most Typhimurium were O-acetylated on rhamnose and abequose residues, while Enteritidis O-antigen had low or no O-acetylation. Both Typhimurium and Enteritidis O-antigen were approximately 20%-50% glucosylated. Amount of S. Typhimurium O-antigen and O-antigen glucosylation level were inversely related. There was no clear association between clinical presentation and antibody susceptibility, O-antigen level or other O-antigen features.

Conclusion/significance: Kenyan S. Typhimurium and Enteritidis clinical isolates are susceptible to antibody-mediated killing, with degree of susceptibility varying with level of O-antigen for S. Typhimurium. This supports the development of an antibody-inducing vaccine against NTS for Africa. No clear differences were found in the phenotype of isolates from blood and stool, suggesting that the same isolates can cause invasive disease and gastroenteritis. Genome studies are required to understand whether invasive and gastrointestinal isolates differ at the genotypic level.

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Related in: MedlinePlus

Correlation of SBA results (a, c) and OAg production levels (b, d) in S. Typhimurium (a, b) and S. Enteritidis (c, d) isolates with clinical presentations.Samples for which no clinical presentation was determined were excluded from analysis. Malawi serum pool was used for SBA. Invasive: Salmonella isolates from blood, urine, CSF. Gastrointestinal: Salmonella isolates from stools. Controls: Salmonella isolates from stools of healthy controls.
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pntd.0003573.g005: Correlation of SBA results (a, c) and OAg production levels (b, d) in S. Typhimurium (a, b) and S. Enteritidis (c, d) isolates with clinical presentations.Samples for which no clinical presentation was determined were excluded from analysis. Malawi serum pool was used for SBA. Invasive: Salmonella isolates from blood, urine, CSF. Gastrointestinal: Salmonella isolates from stools. Controls: Salmonella isolates from stools of healthy controls.

Mentions: No correlation was found between NTS clinical presentation (invasive, gastrointestinal and carrier) and either antibody susceptibility or polysaccharide production, for either S. Typhimurium or S. Enteritidis isolates (Fig. 5). There was no clear correlation between O-acetylation levels/position and glucosylation levels with clinical presentation, antibody susceptibility and OAg production. For S. Typhimurium, we found an association between lower glucosylation levels and higher OAg production (Spearman r = 0.51, 95% CI-0.69 to-0.27, p value<0.001) (Fig. 6).


Relationship between antibody susceptibility and lipopolysaccharide O-antigen characteristics of invasive and gastrointestinal nontyphoidal Salmonellae isolates from Kenya.

Onsare RS, Micoli F, Lanzilao L, Alfini R, Okoro CK, Muigai AW, Revathi G, Saul A, Kariuki S, MacLennan CA, Rondini S - PLoS Negl Trop Dis (2015)

Correlation of SBA results (a, c) and OAg production levels (b, d) in S. Typhimurium (a, b) and S. Enteritidis (c, d) isolates with clinical presentations.Samples for which no clinical presentation was determined were excluded from analysis. Malawi serum pool was used for SBA. Invasive: Salmonella isolates from blood, urine, CSF. Gastrointestinal: Salmonella isolates from stools. Controls: Salmonella isolates from stools of healthy controls.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352093&req=5

pntd.0003573.g005: Correlation of SBA results (a, c) and OAg production levels (b, d) in S. Typhimurium (a, b) and S. Enteritidis (c, d) isolates with clinical presentations.Samples for which no clinical presentation was determined were excluded from analysis. Malawi serum pool was used for SBA. Invasive: Salmonella isolates from blood, urine, CSF. Gastrointestinal: Salmonella isolates from stools. Controls: Salmonella isolates from stools of healthy controls.
Mentions: No correlation was found between NTS clinical presentation (invasive, gastrointestinal and carrier) and either antibody susceptibility or polysaccharide production, for either S. Typhimurium or S. Enteritidis isolates (Fig. 5). There was no clear correlation between O-acetylation levels/position and glucosylation levels with clinical presentation, antibody susceptibility and OAg production. For S. Typhimurium, we found an association between lower glucosylation levels and higher OAg production (Spearman r = 0.51, 95% CI-0.69 to-0.27, p value<0.001) (Fig. 6).

Bottom Line: Typhimurium, but not Enteritidis, O-antigen expression correlated with reduced sensitivity to killing (r = 0.29, 95% CI = 0.10-0.45, p = 0.002).Typhimurium.Genome studies are required to understand whether invasive and gastrointestinal isolates differ at the genotypic level.

View Article: PubMed Central - PubMed

Affiliation: Centre for Microbiology Research (CMR), Kenya Medical Research Institute (KEMRI), Nairobi, Kenya; Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya.

ABSTRACT

Background: Nontyphoidal Salmonellae (NTS) cause a large burden of invasive and gastrointestinal disease among young children in sub-Saharan Africa. No vaccine is currently available. Previous reports indicate the importance of the O-antigen of Salmonella lipopolysaccharide for virulence and resistance to antibody-mediated killing. We hypothesised that isolates with more O-antigen have increased resistance to antibody-mediated killing and are more likely to be invasive than gastrointestinal.

Methodology/principal findings: We studied 192 NTS isolates (114 Typhimurium, 78 Enteritidis) from blood and stools, mostly from paediatric admissions in Kenya 2000-2011. Isolates were tested for susceptibility to antibody-mediated killing, using whole adult serum. O-antigen structural characteristics, including O-acetylation and glucosylation, were investigated. Overall, isolates were susceptible to antibody-mediated killing, but S. Enteritidis were less susceptible and expressed more O-antigen than Typhimurium (p<0.0001 for both comparisons). For S. Typhimurium, but not Enteritidis, O-antigen expression correlated with reduced sensitivity to killing (r = 0.29, 95% CI = 0.10-0.45, p = 0.002). Both serovars expressed O-antigen populations ranging 21-33 kDa average molecular weight. O-antigen from most Typhimurium were O-acetylated on rhamnose and abequose residues, while Enteritidis O-antigen had low or no O-acetylation. Both Typhimurium and Enteritidis O-antigen were approximately 20%-50% glucosylated. Amount of S. Typhimurium O-antigen and O-antigen glucosylation level were inversely related. There was no clear association between clinical presentation and antibody susceptibility, O-antigen level or other O-antigen features.

Conclusion/significance: Kenyan S. Typhimurium and Enteritidis clinical isolates are susceptible to antibody-mediated killing, with degree of susceptibility varying with level of O-antigen for S. Typhimurium. This supports the development of an antibody-inducing vaccine against NTS for Africa. No clear differences were found in the phenotype of isolates from blood and stool, suggesting that the same isolates can cause invasive disease and gastroenteritis. Genome studies are required to understand whether invasive and gastrointestinal isolates differ at the genotypic level.

Show MeSH
Related in: MedlinePlus