There are two main classifications of bacteria: Gram-positive and Gram-negative. Within each of the groupings, there are several types of bacteria. Antibiotic resistance in Gram-negative bacteria has been increasingly challenging for a few key reasons.

Let’s investigate this issue’s causes and discuss some possible solutions.

Gram Negative Bacteria

Using a crystal violet-iodine complex and a safranin counter stain, Hans Christian Gram developed a method in 1884 for distinguishing between Gram-positive and Gram-negative microorganisms [1]. Gram-negative bacteria counterstain with safranin to provide a pink hue because they cannot withstand the complex stain. Gram-positive bacteria exhibit a purple or violet stain. Each bacteria have a unique cell wall structure, which causes this variance.

Gram-Negative Bacteria are becoming More Difficult to Eradicate for the Reasons Listed Below:

Outer Membrane

The outer membrane of Gram-negative bacteria is the main barrier to antibiotics. This additional layer shields the bacteria from many antibiotics and other medications. Lipopolysaccharides (LPS), which are extended chains of sugar molecules that attach to the cell wall, make up the outer membrane. Additionally, LPS has a hydrophobic area, which is a tail that protrudes into the surroundings. This area aids the LPS molecules’ ability to surround the cell with a barrier.

Antibiotics have a harder time penetrating Gram-negative bacteria’s outer membrane and reaching their interiors because of the hydrophobic area of LPS [2]. Additionally, this area shields the bacteria from the effects of the lysozyme enzyme, which tears down the bacterial cell walls.

Utilizing medications that can permeate the outer membrane is one technique to overcome this barrier. Employing antibodies that specifically target LPS molecules is another strategy.

The simulation of LPS bilayers and outer membrane systems is a fundamental part of studying bacteria’s ability to survive in their environment [2]. By further understanding these defenses, we can create more effective antibiotics that are able to bypass them, helping us fight infection better.

Higher Levels of Transport Proteins

Additionally, Gram-negative bacteria have larger concentrations of transport proteins [3], which force drugs out of the cell before they can cause any harm. An outer membrane protein (OMP) and an inner membrane protein make up these proteins, which are found in the inner membrane (IMP).

The antibiotic binding is done by the OMP portion of the transport protein. The antibiotic is removed from the cell by the IMP component.

Drugs that can impede the transport of proteins are one approach to get around this problem. Another method is to utilize drugs that attach to the protein’s OMP portion and stop it from binding to antibiotics.


Because of the development of resistance and spread of resistance antibiotics are sometimes having a tougher time killing Gram-negative bacteria than Gram-positive bacteria for various reasons. They have an exterior membrane that shields them from many medications, which is one explanation. They also contain larger concentrations of transport proteins, which push antibiotics outside of cells before they can cause any harm. Additionally, certain Gram-negative bacteria contain a slime coating that helps them adhere to surfaces and shield them from phagocytosis.

Crestone is a pharmaceutical company in Colorado that focuses on novel antibiotic research and to combat antimicrobial resistance


  1. Gram-positive and gram-negative: What is the difference? (2022, September 29).
  2. Rice, A., Rooney, M. T., Greenwood, A. I., Cotten, M. L., & Wereszczynski, J. (2020). Lipopolysaccharide Simulations Are Sensitive to Phosphate Charge and Ion Parameterization. Journal of Chemical Theory and Computation, 16(3), 1806–1815.
  3. Alpana and Murari Chaudhuri. (2018, October 28). Why are gram-negative bacteria resistant to antibiotics? Medium; The Biochemists.