Naslov
The peculiar phenotype of ΔiglG mutant in human macrophages and mice model

Autori
Ozanic, Mateja ; Marecic, Valentina ; Lindgren, Marie ; Sjöstedt, Anders ; Santic, Marina

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
Host Pathogen Interaction Discussion Forum 2016

Mjesto i datum
Broumov, Češka Republika, 02.05.2016. - 05.05.2016

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Francisella; human macrophages; iglG

Sažetak
Several bacterial pathogens interact with their host through protein secretion involving type VI secretion system (T6SS). Francisella tularensis is a highly pathogenic intracellular bacterium that causes the disease tularemia. Proteins encoded by the Francisella pathogenicity island (FPI), which constitute a type VI secretion system, are essential for the escape of the bacterium from the phagosome followed by productive intracellular replication. It has been shown that T6SS in Francisella is distinct since all substrates of F. tularensis T6SS, except for VgrG, are unique to the species. Many of the FPI proteins were secreted into the macrophage cytosol, dependent on the functional components of DotU, VgrG, IglC and IglG. In addition, PdpC seems to have a regulatory role in expression of iglABCD. Since previous results showed peculiar phenotype of ΔpdpC and ΔiglG mutants in mouse macrophages their unique behavior was further studied in this study. Our results show that both ΔpdpC and ΔiglG mutants of the live vaccine strain (LVS) of F. tularensis did not replicate within human monocytes derived macrophages (hMDM). The ΔpdpC mutant did not escape from the FCV, neither caused cytopythogenicity in primary macrophages and was attenuated in a mice model. Interestingly, ΔiglG mutant escaped from the FCV within hMDMs and caused the pathological changes in the spleen and liver tissues of intradermally infected C57BL/6 mice. The ΔiglG mutant with its unique phenotype could be used as a potential vaccine candidate.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA