Gram negative

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Bacteria are categorised into two main subgroups 'Gram-negative' and 'Gram positive' bacteria (with the exception of Mycobacterium tuberculosis which falls into neither of the two groups.) The Gram method of classification is dependent upon cell wall structure. In this article I am going to focus on the 'Gram-negative' wall structure.

A Gram-negative bacteria has a base lipid bi-layer similar to an eukaryotic plasma membrane, surrounded by the periplasmic space. A thin peptidoglycan layer, much thinner in comparison to that of the gram positive bacteria then arises separating the two periplasmic compartments. Peptidoglycan is a polymer made up of two repeating units of N-acetylmumaric acid and N-acetylglucosamine which form linear chains due to cross-linkages formed by the tetrapeptide side chains of the monomers. The outermost external barrier of a gram-negative bacteria is a lipid-like bi-layer, but this is highly dissimilar from that of a eukaryotic plasma membrane. The inner leaflet of this outer membrane is studded with lipoproteins which associate to the cytoskeleton and peptidoglycan layer. The outer leaflet is made up of LPS lipidpolysaccharide; composed of Lipid A a functional endotoxin when released and an O polysaccharide tail.

Due to the lipid characteristics of the outermost membrane of the cell wall, the gram-negative bacteria are stained pink when gram stained.

Gram-negative refers to a classification of bacteria based on their cell wall structure. Gram-negative bacteria appear red as a result of Gram testing, whereas Gram-positive stain purple.

The structure of the Gram-negative bacterial cell wall is what distinguishes it from Gram-positive bacteria. Gram-negative bacteria contain a much thinner layer of Peptidoglycan in comparison to a Gram-positive bacterial cell wall. The Gram-negative cell wall consists of a unique outer membrane, containing lipopolysaccharides, murein lipoproteins and porin channels. There is also a periplasmic space between the peptidoglycan cell wall, and the cell membrane.

Gram-negative bacteria exhibit stronger resistance to antibiotics such as Lysozyme and penicillin G, as well as greater resistance to dyes and detergents. The lipopolysaccharide consists of a core polysaccharide, Lipid A and O-antigen. This lipolysaccharide layer is important in excluding large hydrophobic substances from interacting with the cell. Lipid A attaches to the outer membrane ensuring that the lipopolysaccharide remains attached to the cell.

Highly Resistant Gram Negative Bacteria

Pseudomonas aeruginosa consisting of Extended-spectrum β-lactamase producing bacteria (ESBL)[1], E. coli, etc. are one of the highly resistant Gram negative bacteria. Antibiotics like Carbapenems, Quinolones, etc. are used to treat Gram negative infections provided adequate source control[2] . However, β-lactamases are bacterial enzymes that provide resistance by cleaving the β-lactam ring of the drugs[3] and the rates of E. coli resistance has been ascending over the years. This again limits the amount of antibiotics available to fight infections and highlights the difficulty level of treating infections caused by Gram negative due to the nature of their cell. Thus, doctors prefer using older drugs like Colistin, to treat the infections which may have toxic side effects[4].  Another method is a combination of two different antibiotics like a beta lactamantibiotic and aminoglycoside, these are both antibiotics with different modes of action so have a higher success against gram-negative infections[5]. Furthermore, chemically modified versions of penicillin with structural differences such as added amino groups are used, this allows the antibiotic to penetrate the outer membrane of gram negative bacteria, so it can reach the peptidoglycan cell wall[6]


  5. Pranita D. Tamma, sara E Cosgrove, lisa L. Maragakis. “Combination therapy for treatment of infections with gram-negative bacteria” clinical microbiology reviews. 2012, 450-470 volume 25 No. 3.
  6. S.K Sharma, Lalit Singh, Suruchi Singh. “Comparative Study between Penicillin and Ampicillin” Scholars Journal of Applied Medical Sciences 2013; 291-294
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