{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:29Z","timestamp":1787022209792,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011400","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n                    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 the cell. Although its polyanionic nature has suggested that it may form a protective shield on the cell surface, its role remains 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 pseudo-capsule was found to be present in specific strains only. To investigate its putative role in host immune evasion mechanisms, such as resistance to serum bactericidal activity, antimicrobial peptides and phagocytosis, the enzymes involved in polyP metabolism were genetically deleted, generating mutants with altered polyP external content. The mutants with lower polyP content on their surface compared to the wild-type strains, became sensitive to complement-mediated killing in presence of normal human serum. Conversely, naturally serum sensitive strains that did not display a significant polyP pseudo-capsule became resistant to complement in the presence of exogenous polyP. The presence of polyP pseudo-capsule was also critical in the protection from antibacterial activity of cationic antimicrobial peptide, such as cathelicidin LL-37. Results showed that the minimum bactericidal concentration was lower in strains lacking polyP than in those harboring the pseudo-capsule. Data referring to phagocytic killing resistance, assessed by using neutrophil-like cells, showed a significant decrease in viability of mutants lacking polyP on their cell surface in comparison to the wild-type strain. The addition of exogenous polyP overturned the killing phenotype of sensitive strains suggesting that gonococcus could exploit environmental polyP to survive to complement-mediated, cathelicidin and intracellular killing. Taken together, data presented here indicate an essential role of the polyP pseudo-capsule in the gonococcal pathogenesis, opening new perspective on gonococcal biology and more effective treatments.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011400","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T13:36:30Z","timestamp":1684762590000},"page":"e1011400","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Functional characterization of the gonococcal polyphosphate pseudo-capsule"],"prefix":"10.1371","volume":"19","author":[{"given":"Benedetta","family":"Manca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Buffi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Magri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Del Vecchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Taddei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Pezzicoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1674-2490","authenticated-orcid":true,"given":"Maria","family":"Giuliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,5,22]]},"reference":[{"key":"ppat.1011400.ref001","unstructured":"WHO. 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Kulakovskaya","year":"2018","journal-title":"World J Microbiol Biotechnol"},{"issue":"4","key":"ppat.1011400.ref037","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01017-20","article-title":"Polyphosphate functions in vivo as an iron chelator and fenton reaction inhibitor","volume":"11","author":"F Beaufay","year":"2020","journal-title":"mBio"},{"issue":"11","key":"ppat.1011400.ref038","doi-asserted-by":"crossref","first-page":"5818","DOI":"10.1074\/jbc.270.11.5818","article-title":"Inorganic polyphosphate in mammalian cells and tissues","volume":"270","author":"KD Kumble","year":"1995","journal-title":"The Journal of biological chemistry"},{"issue":"11","key":"ppat.1011400.ref039","doi-asserted-by":"crossref","first-page":"7675","DOI":"10.1073\/pnas.112210499","article-title":"Inorganic polyphosphate is essential for long-term survival and virulence factors in Shigella and Salmonella spp","volume":"99","author":"KS Kim","year":"2002","journal-title":"Proc Natl Acad Sci U S 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Sarafian","year":"1983","journal-title":"J Infect Dis"},{"issue":"7","key":"ppat.1011400.ref043","doi-asserted-by":"crossref","first-page":"3247","DOI":"10.1128\/IAI.01445-09","article-title":"The oligosaccharide of gonococcal lipooligosaccharide contains several epitopes that are recognized by human antibodies","volume":"78","author":"R Yamasaki","year":"2010","journal-title":"Infection and immunity"},{"issue":"3","key":"ppat.1011400.ref044","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1084\/jem.193.3.281","article-title":"Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae","volume":"193","author":"S Ram","year":"2001","journal-title":"J Exp Med"},{"issue":"5","key":"ppat.1011400.ref045","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1182\/blood-2013-07-515726","article-title":"Polyphosphate suppresses complement via the terminal pathway","volume":"123","author":"JM Wat","year":"2014","journal-title":"Blood"},{"issue":"4","key":"ppat.1011400.ref046","article-title":"Gonococcal lipooligosaccharide sialylation: virulence factor and target for novel immunotherapeutics","volume":"75","author":"S Ram","year":"2017","journal-title":"Pathogens and disease"},{"issue":"4","key":"ppat.1011400.ref047","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1084\/jem.188.4.671","article-title":"Binding of complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae","volume":"188","author":"S Ram","year":"1998","journal-title":"J Exp Med"},{"issue":"5","key":"ppat.1011400.ref048","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1084\/jem.187.5.743","article-title":"A novel sialic acid binding site on factor H mediates serum resistance of sialylated Neisseria gonorrhoeae","volume":"187","author":"S Ram","year":"1998","journal-title":"J Exp 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