布鲁氏菌胞内转运的时空动态调控网络OA

Brucella is a genus of Gram-negative,facultative intracellular bacteria that cause brucellosis,a zoonotic disease.Brucellosis is primarily characterized by abortion and reproductive tract damage,posing a serious threat to the development of the livestock industry and public health security.To elucidate the molecular mechanisms by which Brucella evades host immune clearance and establishes a persistent infection within host cells,and further dissect the key stages of its invasion,intracellular survival,and replication,this review systematically delineates the entire process of Brucella infection of host cells.The bacteria initially utilize their own adhesins to bind with high affinity to specific receptors on the host cell surface,thereby initiating the process of bacterial internalization.This initial binding triggers host cell signaling pathways mediated by Rho family GTPases,leading to actin cytoskeleton rearrangement,which provides a necessary condition for bacterial entry.Upon cellular entry,Brucella employs its type Ⅳ secretion system(T4SS)to secrete various effectors.On the one hand,these effectors intervene in the integrity of the endoplasmic reticulum structure,and on the other hand,they inhibit the stress response of host cells.Concurrently,the bacteria actively recruit autophagy-related proteins,promoting the encapsulation of the bacteria by autophagic vesicles to form Brucella containing vacuoles(BCVs).Subsequently,by modulating vesicular trafficking,the bacteria evade fusion with lysosomes,facilitating the conversion of early Brucella containing vacuoles(eBCVs)into mature,replicative Brucella containing vacuoles(rBCVs).Within rBCVs,the bacteria undergo extensive replication,achieving persistent intracellular survival.Finally,the bacteria egress from the host cell,initiating a new round of infection,potentially via endosome-mediated mechanisms.In summary,Brucella achieves immune evasion and intracellular parasitism through the synergistic action of multiple mechanisms,including low immunogenicity mediated by surface structures,precise manipulation of endoplasmic reticulum and autophagy pathways by T4SS effectors,active guidance via cytoskeleton remodeling,and reprogramming of vesicular transport pathways.These processes constitute the core mechanism of Brucella infection.Elucidating this mechanism provides direct theoretical foundation and practical reference for developing brucellosis control strategies,novel vaccines,optimized diagnostic techniques,and improved clinical treatment regimens.