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d-Alanylation of Lipoteichoic Acids in Streptococcus suis Reduces Association With Leukocytes in Porcine Blood

Streptococcus suis (S. suis) is a common swine pathogen but also poses a threat to human
health in causing meningitis and severe cases of streptococcal toxic shock-like syndrome
(STSLS). Therefore, it is crucial to understand how S. suis interacts with the host immune
system during bacteremia. As S. suis has the ability to introduce d-alanine into its lipoteichoic
acids (LTAs), we investigated the working hypothesis that cell wall modification by LTA
d-alanylation influences the interaction of S. suis with porcine blood immune cells. We created
an isogenic mutant of S. suis strain 10 by in-frame deletion of the d-alanine d-alanyl carrier
ligase (DltA). d-alanylation of LTAs was associated with reduced phagocytosis of S. suis by
porcine granulocytes, reduced deposition of complement factor C3 on the bacterial surface,
increased hydrophobicity of streptococci, and increased resistance to cationic antimicrobial
peptides (CAMPs). At the same time, survival of S. suis was not significantly increased by
LTA d-alanylation in whole blood of conventional piglets with specific IgG. However, we found
a distinct cytokine pattern as IL-1β but not tumor necrosis factor (TNF)-α levels were
significantly reduced in blood infected with the ΔdltA mutant. In contrast to TNF-α, activation
and secretion of IL-1β are inflammasome-dependent, suggesting a possible influence of LTA
d-alanylation on inflammasome regulation. Especially in the absence of specific antibodies,
the association of S. suis with porcine monocytes was reduced by d-alanylation of its LTAs.
This dltA-dependent phenotype was also observed with a non-encapsulated dltA double
mutant indicating that it is independent of capsular polysaccharides. High antibody levels
caused high levels of S. suis—monocyte—association followed by inflammatory cell death
and strong production of both IL-1β and TNF-α, while the influence of LTA d-alanylation of
the streptococci became less visible. In summary, the results of this study expand previous
findings on d-alanylation of LTAs in S. suis and suggest that this pathogen specifically
modulates association with blood leukocytes through this modification of its surface.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:85842
Date07 June 2023
CreatorsÖhlmann, Sophie, Krieger, Ann-Kathrin, Gisch, Nicolas, Meurer, Marita, de Buhr, Nicole, von Köckritz-Blickwede, Maren, Schütze, Nicole, Baums, Christoph Georg
PublisherFrontiers Media S.A.
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation822369

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