Related Experiment Video

Updated: Jul 2, 2026

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Mcl-1 is a key regulator of apoptosis resistance in Chlamydia trachomatis-infected cells

Krishnaraj Rajalingam1, Manu Sharma, Christine Lohmann

  • 1Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany.

Plos One
|September 5, 2008
PubMed

Insights

Chlamydia trachomatis infection confers apoptosis resistance by up-regulating Mcl-1 via Raf/MEK/ERK and PI3K/AKT pathways. Inhibiting these pathways sensitizes infected cells to death, revealing a key immune evasion strategy.

Area of Science:

  • Microbiology
  • Cell Biology
  • Immunology

Background:

  • Chlamydia are obligate intracellular bacteria causing human diseases.
  • Chlamydia-infected host cells exhibit resistance to apoptosis, a crucial immune evasion mechanism.
  • This resistance allows intracellular replication of the pathogen.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying Chlamydia-induced apoptosis resistance.
  • To determine the role of the Raf/MEK/ERK and PI3K/AKT pathways in this process.
  • To identify key molecules involved in maintaining cell survival during Chlamydia infection.

Main Methods:

  • Utilized chemical inhibitors to block Raf/MEK/ERK and PI3K/AKT signaling pathways in C. trachomatis-infected cells.
  • Assessed cell death sensitivity using granzyme B-mediated cytotoxicity assays.
  • Investigated the expression and stability of the anti-apoptotic protein Mcl-1.
  • Examined apoptosis induction via TNF receptor, DNA damage, and stress stimuli.

Main Results:

  • Inhibition of Raf/MEK/ERK and PI3K/AKT pathways sensitized infected cells to granzyme B-induced cell death.
  • Chlamydia infection up-regulates Mcl-1 through the Raf/MEK/ERK pathway and stabilizes it via PI3K.
  • Interference with Mcl-1 up-regulation increased apoptosis sensitivity to various death stimuli.

Conclusions:

  • Mcl-1 up-regulation is essential for maintaining apoptosis resistance in Chlamydia-infected cells.
  • Targeting Mcl-1 or its regulating pathways could be a strategy to combat Chlamydia infections.
  • Understanding these survival mechanisms is key to developing effective treatments against Chlamydia.

More Related Videos

Identification of Host Pathways Targeted by Bacterial Effector Proteins using Yeast Toxicity and Suppressor Screens07:40

Identification of Host Pathways Targeted by Bacterial Effector Proteins using Yeast Toxicity and Suppressor Screens

Published on: October 25, 2019

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro13:20

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro

Published on: July 17, 2018

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Bacterial Phylum Chlamydiae01:29

Bacterial Phylum Chlamydiae

The phylum Chlamydiae or Chlamydiota is composed of a single order, Chlamydiales. This phylum consists entirely of obligate intracellular parasites that infect eukaryotic hosts. While human pathogens within this group have been studied extensively, the phylum encompasses many species capable of interacting with various eukaryotic organisms. Members of Chlamydiae are typically small cocci, approximately 0.5 μm in diameter, and exhibit a distinctive developmental cycle. As is characteristic of...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.