Functional characterization of the gonococcal polyphosphate pseudo-capsule

Manca, Benedetta (2022) Functional characterization of the gonococcal polyphosphate pseudo-capsule, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Biologia cellulare e molecolare, 34 Ciclo.
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Neisseria gonorrhoeae is an exclusively human pathogen able to evade the host immune system through multiple mechanisms. Gonococci accumulate a large portion of phosphate moieties as polyphosphate (polyP) on the exterior of their cells, however its function has not been yet clarified. Although its polyanionic nature has suggested that it may form a protective shield on the cell surface, its role has remained controversial. Taking advantage of a recombinant His-tagged polyP-binding protein, the presence of a polyP pseudo-capsule in gonococcus was demonstrated. Interestingly, the polyP shield was found to be strain specific. To investigate its functional role in host immune evasion, such as resistance to serum bactericidal activity, phagocytosis and antimicrobial peptides, the enzymes involved in polyP metabolism were genetically deleted, generating mutants with altered polyP external production. To this regard, mutants not expressing polyP on their surface, became sensitive to complement-mediated killing in presence of normal human serum. Conversely, naturally serum sensitive strains did not display polyP pseudo-capsule and could reverse their phenotype in the presence of exogenous polyP. Resistance to phagocytic killing was assessed by using differentiated HL60, a validated cell model for gonococcus-neutrophils interaction. Results exhibited a significant increase in viability of strains shielded with polyP in comparison to those lacking it on their surface. Interestingly, the addition of exogenous polyP restored bacterial survival. Finally, the presence of polyP pseudo-capsule was critical also in the protection from antibacterial activity of cationic antimicrobial peptide, like the cathelicidin LL-37. Indeed, results evidenced that the minimum bactericidal concentration was significantly lower in strains lacking polyP than in those harboring the pseudo-capsule, a condition that overturned after the complementation with exogenous polyP. Taken together, data presented have suggested an essential role of polyP pseudo-capsule in the gonococcal pathogenesis, paving the way to a new perspective on gonococcal biology and new treatments.

Tipologia del documento
Tesi di dottorato
Manca, Benedetta
Dottorato di ricerca
Settore disciplinare
Settore concorsuale
Parole chiave
Neisseria gonorrhoeae, serum resistance, antimicrobial peptide, phagocytosis
Data di discussione
30 Marzo 2022

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