Gram Negative Cell Wall – Its Composition, Function, and Structure

What is a gram negative bacterial cell wall?

       Gram-negative bacteria are bacteria that do not keep the crystal violet stain used in the gram staining method of bacterial differentiation. Gram negative bacteria are bounded by a thin peptidoglycan cell wall, which itself is bounded by an outer membrane containing lipopolysaccharide.

       The cell wall of gram-negative bacteria is complex having a thin layer of peptidoglycan layer of 2-7nm and a thick outer membrane of 7-8nm thick. There is a space between the cell membrane and the cell wall, known as periplasm space made up of periplasm. However, it is found in both gram positive and gram-negative, but in gram-negative the periplasmic space is larger.

       These are considered by their cell envelopes, which are composed of a thin peptidoglycan cell wall sandwiched between an inner cytoplasmic membrane and a bacterial outer membrane. The Danish microbiologist Hans Christian Gram 1884 discovered two large groups of Gram positive and Gram negative bacterial cell walls.

What is the periplasmic space?

      In gram-negative, periplasmic space is made up of several proteins that assist in acquiring nutrients such as hydrolytic enzymes that attack the nucleic acids and phosphorylated molecules. The periplasm also comprises structural elements and important environmental detecting molecules. 

      In the 1960s, scientists were trying to understand how toxic enzymes elaborate in the degradation of important biological molecules, such as ribonucleases and phosphatases produced by gram negative bacteria. The periplasmic space also has enzymes that synthesize peptidoglycan and modify contaminated elements that may source harm to the cell.

Also read Endospore: Its definition, structure, and formation

What are the characteristics of gram negative bacterial cell walls?

      Following are the characteristics of gram-negative bacterial cell walls;

  • The cell wall is thin without an outer layer.
  • They have a periplasmic space that separated the outer membrane from the cytoplasmic layer.
  • The periplasmic space has a network of peptidoglycan chains known as the peptidoglycan layer.
  • It Has an outer membrane containing lipopolysaccharides(LPS, which consists of lipid A, core polysaccharide, and O antigen) in its outer leaflet and phospholipids in the inner leaflet.
  • Porins exist in the outer membrane, which acts like pores for a particular molecule.
  • The S-layer is directly attached to the outer membrane rather than to the peptidoglycan.
  • A high percentage of lipids can be found. It contains all types of amino acids. The muramic acid content is less.
  • It has two membrane bilayers termed the outer and inner membranes.
  • Flagella occur on gram-negative and gram-positive bacteria and their presence can be useful in identification.

What is the shape of a gram negative bacterial cell wall?

       Macroscopic observation of gram-negative bacterial cells ranges from rods to bacillus, to cocci to spiral are the most commonly known shapes. For example;

  • Bacillus shaped: 

                     Escherichia coli.

  • Coccobacillus: 

                     Which is a combination of both cocci and bacilli shapes including Hemophilus influenza.

  • Streptobacillus:

                      Rod-shaped that are connected in chains e.g; Streptobacillus moniliformis.

  • Spiral-shaped bacteria:

                       Also called spirochetes. e.g; Chlamydia trachomatis, Treponema pallidum.

  • Filamentous shaped gram-negative have a filament-like shape. E.g; Norcadia spp. 

For further detail read Bacterial Morphology: size, shape, and arrangements

What is the structure of a gram-negative bacterial cell wall?

      The outer membrane lies above the thin peptidoglycan layer. The membrane is made up of Braun’s lipoprotein which is covalently bound to the peptidoglycan embedded in the outer membrane by hydrophobic ends. Braun’s lipoprotein strongly associates the outer membrane and the peptidoglycan.

        The outer membrane is made up of lipopolysaccharides (LPSs)  which are large multiple molecules made up of lipids and carbohydrates. The lipopolysaccharide is made up of three units: 

  1. Lipid A.
  2. The core polysaccharides.
  3. The O side chain.

The most researched gram-negative bacterial lipopolysaccharide is that of Salmonella Typhimurium.

                           The lipid A unit constitutes two glucosamine sugar derivates each containing three fatty acids and pyrophosphate and the left parts of the lipopolysaccharide project out of the surface of the membrane. The lipopolysaccharides are also responsible for protecting the cell wall from external attacks.

            The LPSs have a negative charge liberal the cell surface a negative charge. Thus this stabilizes the membrane structure. Lipid A contributes to the toxic element of the Lipopolysaccharides. The outer membrane of the gram-negative is made up of porin proteins, making it permeable, and allowing the entry of small molecules such as glucose. 

            Specific carriers transport large molecules like Vitamin B12 across the outer membrane. The outer membrane also prevents the loss of components, especially from the periplasmic space.

Gram negative bacterial cell wall

What is the function of gram negative cell wall

LPS performs numerous essential functions

  1. It provides bacteria with a negative charge because the core polysaccharide often has charged sugars and phosphate.
  2. It helps to keep the structure of the outer membrane stable because lipid A is a major part of the outer leaflet of the membrane. 
  3. It helps make a barrier permeable. The shape of LPS and the way LPS molecules interact with each other are thought to stop bile salts, antibiotics, detergents, and other toxic substances that could kill or hurt the bacterium from getting in.
  4. LPS helps keep pathogenic bacteria protected from the host defense system. The O side chain of LPS is also called the O antigen because it makes the body’s immune system to react against bacteria. In this response, antibodies are made that stick to the strain-specific form of LPS that causes the response. For example, microbiologists use the O antigen to interact with strains of Gram-negative bacteria, like E. coli O157. In this case, the O side chain is the antigenic type, which is number 157.
  5. Unfortunately, many bacteria can quickly change the antigenic nature of their O side chains, which makes it hard for the host to defend itself. 
  6. Most important, the fat Endotoxin is a part of LPS that can act as a poison. When LPS or lipid A get into the bloodstream, they cause a type of septic shock that has no direct treatment.

  How are gram negative bacteria resistant to antibiotics?

     Gram-negative bacteria are increasingly becoming resistant to antibiotics. Bacteria may be resistant to certain antibiotics. Bacteria may be resistant because of any of the following:

  • They are naturally resistant to certain antibiotics.
  • They acquire genes from bacteria that have become resistant.
  • Their genes mutate.

How do you treat and isolate gram negative bacteria?

        A few natural antibiotics are garlic, honey, cabbage, grapefruit seed, extra virgin coconut oil, fermented food, and colloidal silver. Natural antibiotics help to kill gram-negative and gram-positive bacteria.

       MacConkey and Blood agar are usually used to isolate gram-negative bacteria, which usually grow within 24 to 48 hours and are subsequently differentiated based on colony morphology and biochemical reactions.

Why are gram negative bacteria important?

        Gram negative bacteria (GNB) are among the world’s most significant public health problems due to their high resistance to antibiotics. These microorganisms have significant clinical importance in hospitals because they put patients in the intensive care unit (ICU) at high risk and lead to high morbidity and mortality.


  • Jawertz M., Aldenberg., Medical Microbiology: 28th Edition
  • The gram-negative bacterial periplasm: Size matters – PMC (
Rimsha Bashir
Rimsha Bashir

Rimsha Saith is a highly knowledgeable microbiologist with a keen interest in the field. Her expertise and passion are in her writing for Microbiology. As a writer, Rimsha has authored numerous articles that have been well-received by both health and medical students and industries.

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