Mycobacterium tuberculosis sigma factor E regulon modulates the host inflammatory response.

نویسندگان

  • Patricia A Fontán
  • Virginie Aris
  • María E Alvarez
  • Saleena Ghanny
  • Jeff Cheng
  • Patricia Soteropoulos
  • Analia Trevani
  • Richard Pine
  • Issar Smith
چکیده

Mycobacterium tuberculosis survives in macrophages and usually subverts the bactericidal mechanisms of these phagocytes. The understanding of this host-pathogen interaction is relevant for the development of new treatments for tuberculosis. The adaptation of M. tuberculosis to intracellular life depends on its ability to regulate the expression of its genes. Sigma factors are important bacterial transcription activators that bind to the RNA polymerase and give it promoter specificity. Sigma factor E (SigE) controls the expression of genes that are essential for virulence. We have identified the SigE regulon during infection of macrophages, and we analyzed the impact of this regulon on the transcriptional response of phagocytes. Our results indicate that SigE regulates the expression of genes involved in the maintenance of M. tuberculosis cell envelope integrity and function during macrophage infection. Analysis of the phagocytes' transcriptional response indicates that the SigE regulon is involved in the modulation of the inflammatory response.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Reduced immunopathology and mortality despite tissue persistence in a Mycobacterium tuberculosis mutant lacking alternative sigma factor, SigH.

The pathogenesis of tuberculosis involves multiple phases and is believed to involve both a carefully deployed series of adaptive bacterial virulence factors and inappropriate host immune responses that lead to tissue damage. A defined Mycobacterium tuberculosis mutant strain lacking the sigH-encoded transcription factor showed a distinctive infection phenotype. In resistant C57BL/6 mice, the m...

متن کامل

A Mycobacterium tuberculosis Sigma Factor Network Responds to Cell-Envelope Damage by the Promising Anti-Mycobacterial Thioridazine

BACKGROUND Novel therapeutics are urgently needed to control tuberculosis (TB). Thioridazine (THZ) is a candidate for the therapy of multidrug and extensively drug-resistant TB. METHODOLOGY/PRINCIPAL FINDINGS We studied the impact of THZ on Mycobacterium tuberculosis (Mtb) by analyzing gene expression profiles after treatment at the minimal inhibitory (1x MIC) or highly inhibitory (4x MIC) co...

متن کامل

The Mycobacterium tuberculosis stress response factor SigH is required for bacterial burden as well as immunopathology in primate lungs.

BACKGROUND Sigma H (sigH) is a major Mycobacterium tuberculosis (Mtb) stress response factor. It is induced in response to heat, oxidative stress, cell wall damage, and hypoxia. Infection of macrophages with the Δ-sigH mutant generates more potent innate immune response than does infection with Mtb. The mutant is attenuated for pathology in mice. METHODS We used a nonhuman primate (NHP) model...

متن کامل

Mycobacterium tuberculosis DosR Regulon Gene Rv2004c Encodes a Novel Antigen with Pro-inflammatory Functions and Potential Diagnostic Application for Detection of Latent Tuberculosis

Approximately 1.7 billion people in the world harbor latent Mycobacterium tuberculosis (Mtb) with a substantial risk of progression to clinical outcome. Containment of these seed beds of Mtb is essential to eliminate tuberculosis completely in high burden settings such as India. Hence, there is an urgent need for the identification of new serological markers for detection or vaccine candidates ...

متن کامل

The Mycobacterium tuberculosis sigma factor sigmaB is required for full response to cell envelope stress and hypoxia in vitro, but it is dispensable for in vivo growth.

The numerous sigma (sigma) factors present in Mycobacterium tuberculosis are indicative of the adaptability of this pathogen to different environmental conditions. In this report, we describe the M. tuberculosis sigma(B) regulon and the phenotypes of an M. tuberculosis sigB mutant strain exposed to cell envelope stress, oxidative stress, and hypoxia. The sigB mutant was especially defective in ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • The Journal of infectious diseases

دوره 198 6  شماره 

صفحات  -

تاریخ انتشار 2008