Related Experiment Video

Updated: Apr 1, 2026

Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
08:38

Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses

Published on: February 22, 2019

6.4K

Enteric pathogens deploy cell cycle inhibiting factors to block the bactericidal activity of Perforin-2

Ryan M McCormack1, Kirill Lyapichev1, Melissa L Olsson1

  • 1Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States.

Elife
|September 30, 2015
PubMed

Insights

Perforin-2, an innate immune protein, is monoubiquitylated by a cullin-RING E3 ubiquitin ligase (CRL) complex, which is crucial for its bacterial killing activity. Pathogen factors that block this ubiquitylation disable Perforin-2

Area of Science:

  • Immunology
  • Microbiology
  • Molecular Biology

Background:

  • Perforin-2 (MPEG1) is a key component of the innate immune system.
  • It effectively combats Gram-negative, Gram-positive, and acid-fast bacteria.
  • Its role in limiting bacterial proliferation and spread is well-established.

Purpose of the Study:

  • To investigate the molecular mechanisms regulating Perforin-2 activity.
  • To understand how bacterial pathogens interfere with Perforin-2 function.
  • To elucidate the role of ubiquitylation in Perforin-2-mediated bacterial killing.

Main Methods:

  • Utilized biochemical assays to study Perforin-2 ubiquitylation.
  • Investigated the interaction between Perforin-2 and the cullin-RING E3 ubiquitin ligase (CRL) complex.
  • Examined the impact of pathogen-associated molecular patterns (PAMPs) like LPS on Perforin-2.
  • Studied the effect of bacterial effector proteins (Cifs) on NEDD8 and CRL activity.
  • Assessed Perforin-2 redistribution and bactericidal activity in response to Cif.

Main Results:

  • Demonstrated that a CRL complex, including cullin-1 and βTrCP, monoubiquitylates Perforin-2 upon PAMP stimulation.
  • Showed that ubiquitylation is essential for Perforin-2's bactericidal activity and triggers its redistribution.
  • Revealed that enteric pathogens inject cell cycle inhibiting factors (Cifs) that deamidate NEDD8.
  • Established that Cif inhibits CRL activity, thereby blocking Perforin-2 trafficking and bactericidal function.
  • Confirmed that this mechanism disarms host cells against intracellular and extracellular bacteria.

Conclusions:

  • Perforin-2's bactericidal activity is tightly regulated by monoubiquitylation.
  • Bacterial pathogens have evolved mechanisms to evade Perforin-2 by inhibiting its ubiquitylation.
  • Understanding these molecular interactions is critical for developing new strategies against bacterial infections.
Keywords:
CifE. coliEPECMPEG1NEDD8Perforin-2Yersinia pseudotuberculosishumanimmunologyinfectious diseasemicrobiologymouse

More Related Videos

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling08:51

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling

Published on: June 25, 2015

9.7K
Invasion of Human Cells by a Bacterial Pathogen07:15

Invasion of Human Cells by a Bacterial Pathogen

Published on: March 21, 2011

35.5K

Related Concept Videos

Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
84
Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
3.5K
Colonisation of Pathogens01:25

Colonisation of Pathogens

Pathogen colonization of host tissues is a critical step in the development of infectious diseases. Various pathogenic microorganisms, including bacteria, fungi, viruses, and protozoa, have evolved complex strategies to attach to, invade, and persist within host environments. These mechanisms enable pathogens to establish infections, evade immune responses, and resist antimicrobial treatments.Attachment to Host CellsIn bacteria, colonization typically begins with adherence to host epithelial...
35
Antimicrobial Proteins01:23

Antimicrobial Proteins

Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
15.4K
Bacterial Toxins01:12

Bacterial Toxins

Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
51
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
10.5K