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2022 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 1 1, article id e0261938Article in journal (Refereed) Published
Abstract [en]
Francisella tularensis is a highly pathogenic intracellular bacterium that causes the disease tularemia. While its ability to replicate within cells has been studied in much detail, the bacterium also encodes a less characterised type 4 pili (T4P) system. T4Ps are dynamic adhesive organelles identified as major virulence determinants in many human pathogens. In F. tularensis, the T4P is required for adherence to the host cell, as well as for protein secretion. Several components, including pilins, a pili peptidase, a secretin pore and two ATPases, are required to assemble a functional T4P, and these are encoded within distinct clusters on the Francisella chromosome. While some of these components have been functionally characterised, the role of PilO, if any, still is unknown. Here, we examined the role of PilO in the pathogenesis of F. novicida. Our results show that the PilO is essential for pilus assembly on the bacterial surface. In addition, PilO is important for adherence of F. novicida to human monocyte-derived macrophages, secretion of effector proteins and intracellular replication. Importantly, the pilO mutant is attenuated for virulence in BALB/c mice regardless of the route of infection. Following intratracheal and intradermal infection, the mutant caused no histopathology changes, and demonstrated impaired phagosomal escape and replication within lung liver as well as spleen. Thus, PilO is an essential virulence determinant of F. novicida.
Place, publisher, year, edition, pages
Public Library of Science, 2022
National Category
Microbiology in the medical area Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-192161 (URN)10.1371/journal.pone.0261938 (DOI)000792720400017 ()2-s2.0-85123542882 (Scopus ID)
Funder
Swedish Research Council, 2020-01362Region Västerbotten, RV-939171The Kempe Foundations, JCK-1624
2022-02-042022-02-042023-09-05Bibliographically approved