Apoptosis observed in BALB/3T3 cells having ingested Staphylococcus aureus

M Murai1, J Sakurada, K Seki

  • 1Department of Microbiology, The Jikei University School of Medicine, Tokyo, Japan. murai-miyo@spu.ac.jp

Insights

Internalized Staphylococcus aureus can escape host cells, multiply, and trigger apoptosis in fibroblasts. This study details the intracellular mechanisms of S. aureus infection in BALB/3T3 cells.

Area of Science:

  • Microbiology
  • Cell Biology
  • Immunology

Background:

  • Staphylococcus aureus is known to be internalized by murine fibroblasts.
  • The intracellular behavior of S. aureus within host cells remains incompletely understood.

Purpose of the Study:

  • To investigate the intracellular events following the ingestion of Staphylococcus aureus by BALB/3T3 fibroblast cells.
  • To elucidate the mechanisms by which S. aureus interacts with and affects host cells.

Main Methods:

  • BALB/3T3 cells were infected with S. aureus strains (A191, A151, Cowan I).
  • Cells were treated with lysostaphin to assess bacterial viability.
  • DNA fragmentation was analyzed using DNA laddering and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay.
  • Transmission electron microscopy (TEM) was used to visualize intracellular bacterial behavior and host cell morphology.

Main Results:

  • S. aureus strain A191 escaped the endosome, multiplied intracellularly, and induced apoptosis in BALB/3T3 cells within 4 hours.
  • Strain A151 remained largely contained within the endosome and showed limited intracellular multiplication.
  • The Cowan I strain also induced DNA fragmentation, indicating apoptosis, at a slower rate.
  • Apoptotic features observed included electron-dense nuclei and plasma membrane blebbing.

Conclusions:

  • Internalized Staphylococcus aureus can exhibit different intracellular fates depending on the strain.
  • Escape from the endosome, intracellular multiplication, and subsequent induction of apoptosis are key events in S. aureus-induced fibroblast cell death.
  • These findings provide insights into the pathogenesis of S. aureus infections at the cellular level.

Related Concept Videos

Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
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...
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...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
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...