Dissecting the disarming of macrophages by the respiratory pathogen <i>Legionella pneumophila</i>

In L<i>. pneumophila</i> isolates the homologue LegA2 is the most conserved family member, whereas LtpB and some other homologues such as Lpp2048 are found sporadically together with LegA2. While legA2 seems to be part of the core genome, ltpB is located in a putative genomic island suggesting that it might move via horizontal gene transfer. Analysis of the predicted structure and biophysical properties of the proteases suggests that they localise to a mostly hydrophilic environment such as the host cell cytosol.

Immunofluorescence microscopy experiments demonstrated the localisation of the putative proteases in the cytosol of host cells during infection. Ectopic-expression experiments recapitulated the cytoplasmic localisation and showed that the effectors do not cause cell rounding or cytotoxicity. <i>L. pneumophila</i> ΔltpB knockout mutants showed a statistically significant reduction in virulence compared to a wildtype strain in the <i>Galleria mellonella</i> infection model.

From this, we can surmise that LtpB and LegA2 are Dot/Icm T4SS effectors that localise to the host cell cytosol and in the case of LtpB contribute to the virulence of <i>L. pneumophila</i>.<br><br><i>Thesis is embargoed until 31 December 2029.</i><br><br><br>