| Tuberculosis(TB),caused by Mycobacterium tuberculosis,remains one of the most devastating diseases that threatening global public health.About one-third of the world's population is latently infected with this pathogen and 2 million die every year.During coevolution with their hosts,Mycobacterium tuberculosis has evolved a variety of survival strategies to modulate and evade the host macrophage immune response,and persist for many years.Although the emergence of anti-tuberculosis drugs and new vaccines,the irrational use of antibiotics caused the emergence of multidrug resistant(MDR),extensive drug resistant(XDR),even totally drug resistant(TDR)strains and co-infection with HIV,which further aggravate this disease situation.Therefore,in-depth understanding of the M.tuberculosis biology,and developing new drugs are urgent.One significant feature of the M.tuberculosis genome is that it contains two kind of polygenes family encoding PE/PPE proteins,which account for approximately 10%of the coding capacity of their genome.PE/PPE family proteins,which are unique to mycobacteria and mainly present in pathogenic mycobacteria.These family proteins might be virulence factors,which associated with the M.tuberculosis antigen presentation,antigen variation and regulation of macrophage immune function.It is has been reported that some PE/PPE proteins are usually up-regulated expression during the course of infection host macrophage,besides,many PE/PPE proteins are secreted to the mycobacteria cell surface involved in mycobacterium virulence.There only a few of the PPE family proteins function has been characterized,the majority of members of this family are unknown.Until now,there is little researchon the function of PPE25 protein in M.tuberculosis.It had shown that M.avium gene MAV2928(52% homologous to Rv1787)transposon insertion mutation reduced bacterial intracellular survival and prevented phagosome–lysosome fusion.In addition,MAV2928 can interact with MAV2921(ESAT-6 family protein,ESX-N).The M.tuberculosis ESX-5 gene cluster deletion experiment revealed that ?PPE25-PE19 mutant strain reduced intracellular survival in macrophage and immunodeficiency mouse.These results suggested that PPE25 probably involved in the interaction between mycobacterium and host.M.tuberculosis PPE25(Rv1787),a typical member of ESX-5-encoded PPE family protein,was characterized in this study.In order to explore the role of PPE25 in response to hostile environmental stressors and pathogen-host interaction,we constructed the recombinant M.smegmatis expressing PPE25 and M.smegmatis harboring the vector only.Our study demonstrated that Rv1787 was a cell wall associated protein and exposed to cell wall by subcellular localization,and the overexpression of Rv1787 protein can alter colony morphology,sliding ability and biofilm formation of M.smegmatis.The overexpression of Rv1787 protein enhanced the survival rate of recombinant M.smegmatis under oxidation stress conditions(H2O2,diamide)in vitro.Compared with control M.smegmatis,overexpression of the Rv1787 protein in recombinant M.smegmatis enhanced the intracellular survival during infection.Besides,recombinant M.smegmatis Ms_Rv1787 altered the production of cytokines,including TNF-?,IL-6,IL-1?,IL-12p40 and SOCS3,of which the SOCS3 protein up-regulated expression probably involved in inhibiting the expression of proinflammatory cytokines.In conclusion,our experimental results show that the PPE family protein Rv1787 is a cell-associated protein and exposed to the cell wall.The Rv1787 protein enhanced the tolerance of recombinant M.smegmatis to oxidation stress condition;the Rv1787 protein enhanced intracellular suviral of M.smegmatis within macrophages.By upregulating the expression of SOCS3 protein,induced low levels of proinflammatory cytokines expression.Compared with control strain Ms_pNIT,recombinant M.smegmatis Ms_Rv1787 promote macrophage apoptosis.Therefore,our study might provide new clues on how PPE family protein Rv1787 interacts with the host cells. |
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