The putative Type 4 secretion system effector BspD is involved in maintaining envelope integrity of the pathogenBrucella

Author:

Ketterer MarenORCID,Chiquet Petra,Sedzicki Jaroslaw,Québatte MaximeORCID,Dehio ChristophORCID

Abstract

AbstractBrucellosis is a debilitating disease caused by the Gram-negative, facultative intracellular zoonotic pathogenBrucella.En routeto its intracellular replicative niche,Brucellaencounters various stressful environments that may compromise envelop integrity. Here we show, that the proposed Type 4 secretion system (T4SS) effector BspD is a conserved protein of the Rhizobiales, which does not show signs of co-evolution with the presence of a T4SS or a certain lifestyle. We further present data indicating that BspD is critical forBrucella abortusenvelope integrity in the stationary phase and in the presence of EDTA, a compound known to destabilize the outer membrane. Deletion ofbspDresulted in abnormal bacterial morphologies, indicating its involvement in maintaining envelope integrity. Additionally, the absence of BspD led to the formation of fewer and smaller intracellular microcolonies in a macrophage infection model. From our observations, we propose that BspD ofB. abortusis critical for preserving the integrity of the bacterial envelope, particularly under stressful conditions, which may enhanceBrucella’s ability to survive within host cells.ImportanceBrucellosis, caused by the intracellular pathogenBrucella, poses a significant health threat. Understanding howBrucellaadapts to stressful environments is crucial. This study unveils BspD, a conserved protein within the Rhizobiales order, as a key player in maintainingBrucella’s envelope integrity. Remarkably, BspD’s function appears independent of the presence of a Type 4 Secretion System (T4SS) or specific lifestyle. Deletion ofbspDresulted in compromised envelope integrity, abnormal bacterial morphologies, and reduced intracellular microcolony formation. These findings underscore BspD’s critical role, particularly in stressful conditions like the stationary phase and EDTA exposure, and highlight its significance inBrucella’s survival within host cells. This elucidation deepens our understanding ofBrucellapathogenesis and may inform future therapeutic strategies against brucellosis.

Publisher

Cold Spring Harbor Laboratory

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