کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8485345 | 1551711 | 2016 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mycobacterium tuberculosis EsxO (Rv2346c) promotes bacillary survival by inducing oxidative stress mediated genomic instability in macrophages
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کلمات کلیدی
O.DIL-12PCDNF-κBMTBIL-10MSMCFURNSiNOSNACFBSMycobacterium smegmatis3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide - 3- (4،5-dimethylthiazol-2-yl) -2،5-difenyltetrazolium bromideMOI - MEMTT - MTTROS - ROSInterleukin 10 - اینترلوکین 10interleukin 12 - اینترلوکین 12Survival - بقاGenomic instability - بی ثباتی ژنوم Oxidative stress - تنش اکسیداتیوtumor necrosis factor alpha - تومور نکروز عامل آلفاSOD - سدfetal bovine serum - سرم جنین گاوinducible nitric oxide synthase - سنتاز اکسید نیتریک القاییSuperoxide dismutase - سوکسوکس دیسموتازTNF-α - فاکتور نکروز توموری آلفاMacrophages - ماکروفاژها،درشت خوارهاMycobacterium tuberculosis - مایکوباکتریوم توبرکلوزیسProgrammed cell death - مرگ برنامهریزی شده یاختهwild type - نوع وحشیNitric oxide - نیتریک اکسیدN-acetyl cysteine - نیتستیل سیستئینmultiplicity of infection - چندین عفونتoptical density - چگالی نوریcolony forming unit - کلنی واحد تشکیلreactive nitrogen species - گونه های واکنش پذیر نیتروژنReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
میکروبیولوژی و بیوتکنولوژی کاربردی
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چکیده انگلیسی
Mycobacterium tuberculosis (Mtb) survives inside the macrophages by modulating the host immune responses in its favor. The 6-kDa early secretory antigenic target (ESAT-6; esxA) of Mtb is known as a potent virulence and T-cell antigenic determinant. At least 23 such ESAT-6 family proteins are encoded in the genome of Mtb; however, the function of many of them is still unknown. We herein report that ectopic expression of Mtb Rv2346c (esxO), a member of ESAT-6 family proteins, in non-pathogenic Mycobacterium smegmatis strain (MsmRv2346c) aids host cell invasion and intracellular bacillary persistence. Further mechanistic studies revealed that MsmRv2346c infection abated macrophage immunity by inducing host cell death and genomic instability as evident from the appearance of several DNA damage markers. We further report that the induction of genomic instability in infected cells was due to increase in the hosts oxidative stress responses. MsmRv2346c infection was also found to induce autophagy and modulate the immune function of macrophages. In contrast, blockade of Rv2346c induced oxidative stress by treatment with ROS inhibitor N-acetyl-L-cysteine prevented the host cell death, autophagy induction and genomic instability in infected macrophages. Conversely, MtbÎRv2346c mutant did not show any difference in intracellular survival and oxidative stress responses. We envision that Mtb ESAT-6 family protein Rv2346c dampens antibacterial effector functions namely by inducing oxidative stress mediated genomic instability in infected macrophages, while loss of Rv2346c gene function may be compensated by other redundant ESAT-6 family proteins. Thus EsxO plays an important role in mycobacterial pathogenesis in the context of innate immunity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Tuberculosis - Volume 96, January 2016, Pages 44-57
Journal: Tuberculosis - Volume 96, January 2016, Pages 44-57
نویسندگان
Soumitra Mohanty, Michael Dal Molin, Geetanjali Ganguli, Avinash Padhi, Prajna Jena, Petra Selchow, Srabasti Sengupta, Michael Meuli, Peter Sander, Avinash Sonawane,