Cell Wall–Deficient Bacteria

Although most prokaryotes cannot survive in nature without their cell walls, some do so naturally. These include the mycoplasmas, a group of pathogenic bacteria that causes several infectious diseases of humans and other animals, and the Thermoplasma group, species of Archaea that naturally lack cell walls.

These bacteria are able to survive without cell walls because they either contain unusually tough cytoplasmic membranes or because they live in osmotically protected habitats such as the animal body.

Cell Wall-Deficient Bacteria

  1. Mollicutes (often known as Mycoplasma species)
  2. L-forms
  3. Spheroplasts
  4. Protoplasts


The Mollicutes, often called mycoplasmas, are naturally occurring stable bacteria that lack cell walls (mollis is latin for “soft”). These pleomorphic bacteria are not stained by Gram-stain but are phylogenetically related to Firmicutes (a phylum of bacteria, most of which have Gram-positive cell wall structure).

Mycoplasma (cell wall-deficient bacteria)

Mycoplasma (cell wall-deficient bacteria) resemble protoplasts (bacteria treated to remove their cell walls) but are more resistant to osmotic lysis than protoplasts. Species of medical importance include Mycoplasma pneumoniae and Ureaplasma urealyticum.

Characteristics feature

  1. They are among the smallest living microorganisms capable of independent existence, ranging in size from 0.1-0.2 μm, approximately the size of the largest viruses (the poxviruses).
  2. Cytoplasmic membranes of mycoplasmas are more stable than that of other bacteria due to the presence of sterols. Sterols add strength and rigidity to the cytoplasmic membranes.
  3. The genomes of mycoplasmas are between 500 and 1100 kilobase pairs of DNA in most cases. This is smaller than those of most bacteria, comparable to the genome size of the obligately parasitic chlamydia and rickettsia.
  4. Mycoplasmas give a characteristic “fried-egg” appearance in solid culture media consisting of a dense central core that penetrates downward into the agar, surrounded by a circular spreading area that is lighter in color.
  5. Growth of mycoplasmas is not inhibited by antibiotics such as penicillin that inhibit cell wall synthesis. However, mycoplasmas are as sensitive as most Bacteria to antibiotics whose targets are other than the cell wall.
  6. Certain mycoplasma contains compounds called lipglycans, a lipopolysaccharide-like biomolecule that lacks lipid A backbone. Lipoglycans are long-chain heteropolysaccharides covalently linked to membrane lipids and embedded in the cytoplasmic membrane of many mycoplasmas.  Lipoglycans stabilize the cytoplasmic membrane and also facilitates attachment of mycoplasms to cell surface receptors of animal cells.
  7. Media for the culture of most mycoplasmas are typically quite complex requiring unsaturated fatty acids, sterols, vitamins, amino acids, purines, and pyrimidines as growth factors.
  8. Oxygen requirements of mycoplasmas vary widely, some are strictly respiratory while others are facultative or even obligate anaerobes. 
Fried egg colonies of Mycoplasma (cell wall-deficient bacteria)
Fried egg colonies of Mycoplasma (source)

Some mycoplasmas require sterols in their growth media. Based on sterol requirements, mycoplasmas can be differentiated into two groups.

Requires sterolsDo not require sterols
The proposed life cycle of cell wall-deficient bacteria
(Image source)


L-forms bacteria, also known as L-phase bacteria are mutant bacteria without a cell wall, usually produced in the laboratory but sometimes formed in the body of patients being treated with penicillin. They can reproduce on ordinary culture media.

L-forms are completely resistant to most antibiotics working specifically on cell wall synthesis, such as penicillins and cephalosporins. L‐forms are able to grow as spheroplasts or protoplasts.

L form of bacteria


Protoplasts are unstable cells with all the rigid wall layers lost artificially. The cell wall is lost due to the action of lysozyme enzymes which destroy peptidoglycan. Protoplasts are metabolically active but unable to reproduce and are easily lysed.

If bacteria are incubated with penicillin in an isotonic solution, gram-positive bacteria are converted to protoplasts and continue to grow normally when isotonicity is maintained.


A spherical, osmotically sensitive cell derived from a bacterium by loss of some but not all of the rigid wall layer.  

Spheroplasts are spherical, osmotically sensitive cells derived from Gram-negative bacteria by loss of some but not all of the rigid wall layer. The damage in the wall is caused by a toxic chemical or antibiotic such as penicillin (gram-negative bacteria retain their outer membrane after penicillin treatment). They are able to change back to their normal form when the toxic agent is removed.

Archaea lacking cell walls

Photo by Dr. William Hixon

Cells of some Archaea, such as Thermoplasma and Ferroplasma, lack cell walls. Thermoplasma is a chemoorganotroph that grows optimally at 55°C and pH 2 in complex media. The cytoplasmic membrane of Thermoplasma contains a lipopolysaccharide-like material called lipoglycan. This substance consists of a tetraether lipid monolayer membrane with mannose and glucose. The membrane also contains glycoproteins but not sterols. These molecules render the Thermoplasma membrane stable to hot, acidic conditions.

Ferroplasma is a chemolithotrophic relative of Thermoplasma and is a strong acidophile.

References and further readings

  1. Madigan Michael T, Bender, Kelly S, Buckley, Daniel H, Sattley, W. Matthew, & Stahl, David A. (2018). Brock Biology of Microorganisms (15th Edition). Pearson.
  2. Allan, E. J., Hoischen, C., & Gumpert, J. (2009). Bacterial L-forms. Advances in Applied Microbiology, 68, 1–39. https://doi.org/10.1016/S0065-2164 (09)01201-5
  3. Onwuamaegbu, M., Belcher, R., & Soare, C. (2005). Cell Wall-Deficient Bacteria as a Cause of Infections: A Review of the Clinical Significance. Journal of International Medical Research, 33(1), 1–20. https://doi.org/10.1177/147323000503300101

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

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