Gram-negative Bacteria

The Gram stain test, developed in the 1800s by Hans Christian Gram, is a method for classifying different types of bacteria using a chemical stain and viewing through a microscope the results on the bacteria’s protective cell wall. Most bacteria are classified into two groups—Gram-positive or Gram-negative—depending on whether they retain a specific stain color.  Gram-positive bacteria retain a purple-colored stain, while Gram-negative bacteria appear pinkish or red.

Gram-negative bacteria can cause many types of infections and are spread to humans in a variety of ways. Several species, including Escherichia coli, are common causes of foodborne disease. Vibrio cholerae—the bacteria responsible for cholera—is a waterborne pathogen. Gram-negative bacteria can also cause respiratory infections, such as certain types of pneumonia, and sexually transmitted diseases, including gonorrhea. Yersinia pestis, the Gram-negative bacterium responsible for plague, is transmitted to people through the bite of an infected insect or handling an infected animal.

Increasing Concern About Drug Resistance

Gram-negative bacteria

The image on the left shows Gram-positive bacteria, which retain a purple stain. The image on the right is Gram-negative bacteria, which appear pink or red.

Centers for Disease Control and Prevention

Certain types of Gram-negative bacteria have become increasingly resistant to available antibiotic drugs. Some strains are now resistant to many, most, or all available treatments resulting in increased illness and death from bacterial infections, and contributing to escalating healthcare costs. Examples of Gram-negative bacteria that have demonstrated drug resistance include

  • E. coli, which causes the majority of urinary tract infections
  • Acinetobacter baumanii, which causes disease mainly in healthcare settings. In addition, wound infections caused by Acinetobacter have been found in U.S. military personnel who were deployed to Iraq and Afghanistan.
  • Pseudomonas aeruginosa, which causes bloodstream infections and pneumonia in hospitalized patients. It is a common cause of pneumonia in patients with cystic fibrosis.
  • Klebsiella pneumoniae, which causes many types of healthcare-associated infections, including pneumonia, urinary tract infections, and bloodstream infections
  • Neisseria gonorrhoeae, which causes the sexually transmitted disease gonorrhea, is the second most commonly reported infectious disease in the United States.


Drug-resistant Gram-negative infections, such as Klebsiella, Pseudomonas, and Acinetobacter, have emerged as major concerns in hospitals, nursing homes and other healthcare settings. In some cases, bacteria can enter the body through urinary and intravenous catheters, ventilators, or wounds and can lead to pneumonia and infections of the bloodstream, bones, joints, and urinary tract. These types of infections disproportionately affect the very ill and the elderly and are often difficult to treat.


Many Gram-negative bacterial infections occur through cross-contamination between people. Simple measures, such as hand washing and having healthcare workers wear gloves and gowns, can significantly reduce the spread of bacteria. Vaccines are not available for most healthcare-associated infections caused by Gram-negative bacteria.


Treating Gram-negative bacterial infections can be difficult because of several unique features of these bacteria. For example, the unique nature of their cell wall makes them resistant to several classes of antibiotics. Infections have typically been treated with broad-spectrum antibiotics, such as beta-lactams followed by carbapenems. However, even these drugs have become ineffective against some bacteria, leaving healthcare providers no choice but to use older drugs, such as colistin, which can have toxic side effects.


New drugs to combat Gram-negative bacterial infections are needed. NIAID supports basic, translational and clinical research into the development of new and effective drugs and other treatments. In addition, researchers are unraveling the molecular mechanisms of drug resistance in Gram-negative bacteria to identify novel strategies to combat these pathogens. NIAID-funded researchers are exploring these and other questions related to Gram-negative bacteria and the diseases they cause.​​​​​

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