Gram-negative bacteria give negative results on the Gram staining technique, hence named gram-negative bacteria. These are bacteria with solid walls.
These bacteria don’t retain the crystal violet dye and appear red-colored when viewed under a microscope on a Gram stain test.
Neisseria, Salmonella, E.coli, and Campylobacter are some examples of gram-negative bacteria.
Gram-negative bacteria were described for the first time in 1884 by Christian Gram, a Danish scientist in Berlin when he visualized Klebsiella pneumoniae in the lungs of people by using the Gram staining technique. These patients died because of pneumonia infection.
Gram-negative bacteria are listed among the most common public health problems because of their high antibiotic resistance.
These are also clinically important in hospital settings because patients admitted in the wards or intensive care units are at higher risk, which leads to increased morbidity and mortality. Gram-negative bacteria are important causes of nosocomial diseases.
Characteristics
- Gram-negative bacteria are enclosed in a protective capsule.
- Under this capsule, these have an outer membrane that protects them against antibiotics.
- Gram-negative bacteria release endotoxins that contribute to the severity of symptoms during infections.
- The peptidoglycan layer of gram-negative bacteria is thin compared to gram-positive bacteria. It is usually sandwiched between the outer membrane and the inner cytoplasmic membrane. That’s why these bacteria can be stained by the counterstain.
- Gram-negative bacteria are even more pathogenic than gram-positive bacteria due to their low susceptibility to antibiotics.
- Gram-negative bacteria have porins that regulate the transport of molecules inside and outside of the cell.
Structure of the cell envelope and diagram
The cell envelope of gram-negative bacteria is very different from gram-positive bacteria. These have an outer membrane containing lipopolysaccharides, a thin peptidoglycan layer, and an inner cytoplasmic membrane.
- Gram-negative bacteria have a thin cell wall that contains a monolayer of peptidoglycan that is partially cross-linked.
- The cell wall of gram-negative bacteria doesn’t have teichoic acid.
- The cell envelope outside the cell wall is called an outer membrane.
- The outer membrane of the gram-negative bacteria has lipopolysaccharides and porins.
- Lipopolysaccharides serve as endotoxins. It is a large molecule that varies in composition from one bacterial species and strain to another. It is a potent virulence factor and contributes to the structural integrity of gram-negative bacteria.
- Porins transport the molecules in and out of the cell.
- The outer membrane of the cell is anchored into lipoproteins through a non-covalent bond, called Braun’s lipoproteins, which are further bound to the peptidoglycan layer through a covalent bond.
- There is a periplasmic space between the outer membrane and the inner membrane with the structural polymer peptidoglycan.
- The inner cytoplasmic membrane has lipoproteins, transmembrane proteins, or peripheral membrane proteins.
- Lipoproteins are present in the outer lipid bilayer leaflet, and peripheral membrane proteins lie adjacent to the bilayer leaflets.
Classification
Gram-negative bacteria are classified into two major categories; Cocci and Rods.
Gram Negative bacteria list
Gram-negative cocci
Gram-negative cocci include the four types
- Neisseria gonorrhoeae – that cause a sexually transmitted disease
- Neisseria meningitides – that cause meningitis
- Moraxella catarrhalis – that cause respiratory symptoms
- Haemophilus influenzae – that cause respiratory symptoms
Image source: wikimedia
Gram-negative rods
Gram-negative rods are classified into three categories;
- Facultative
- Aerobic
- Anaerobic rods
Image source: wikimedia
1. Facultative rods
- Facultative rods have two further categories; straight and curved.
- Straight facultative rods include respiratory, zoonotic, and enteric organisms.
- Hemophilis, Bordetella, and Legionella are examples of respiratory straight facultative rods.
- Zoonotic straight facultative rods have Brucella, Francisella, Yersinia, etc. Escherichia, Enterobacter, Salmonella, Shigella, and some others are included in enteric straight facultative rods.
Curved facultative rods have Campylobacter, Helicobacter, and Vibrio.
2. Aerobic rods
Aerobic rods include Pseudomonas that cause pneumonia and urinary tract infections.
3. Anaerobic rods
Anaerobic rods have Bacteroides that cause peritonitis.
List of infections caused by gram-negative bacteria
Following infections are caused by gram-negative bacteria.
| Organism (Genus) | Representative diseases |
| Neisseria | Gonorrhea, Meningitis |
| Haemophilus | Meningitis |
| Bordetella | Whooping cough |
| Legionella | Pneumonia |
| Brucella | Brucellosis |
| Francisella | Tularemia |
| Pasteurella | Cellulitis |
| Yersinia | Plague |
| Escherichia | Urinary Tract Infection, Diarrhea |
| Enterobacter | Urinary Tract Infection |
| Serretia | Pneumonia |
| Klebsiella | Pneumonia, Urinary Tract Infection |
| Salmonella | Enterocolitis, Typhoid fever |
| Shigella | Enterocolitis |
| Proteus | Urinary Tract Infection |
| Campylobacter | Enterocolitis |
| Helicobacter | Gastritis, Peptic ulcer |
| Vibrio | Cholera |
| Pseudomonas | Pneumonia, Urinary tract infections |
| Bacteroides | Peritonitis |
Risk factors for Developing Gram-Negative Bacterial Infections
These are the most common infections in hospital settings. And the risk increases if you stay longer in the hospital.
The risk of infection also increases in the following;
- Undergoing dialysis for kidney diseases
- Weak immune system
- War wounds
- Catheterisation
- Being on a ventilator / Mechanical ventilation
- Recent surgery
Antibiotics for gram-negative bacteria
Gram-negative bacteria are mostly associated with severe, life-threatening infections. These can involve the bloodstream, surgical site, urinary tract, lungs, etc. Despite the use of antibiotics, gram-negative infections are commonly associated with high morbidity and mortality.
It means that multi-drug resistance (MDR) is a crucial factor. The World Health Organization (WHO) has stated that antimicrobial resistance is one of the three most critical problems for human health.
The most commonly used antibiotics for the treatment of gram-negative bacteria are following
- Cephalosporins: For example ceftriaxone–cefotaxime, ceftazidime
- Broad-spectrum penicillins with or without β-lactamase inhibitors: For example amoxicillin-clavulanic acid, piperacillin-tazobactam
- Tetracyclines
- Aminoglycosides: For example gentamicin, amikacin
- Fluoroquinolones: For example, ciprofloxacin, levofloxacin
- Carbapenems
- Fosfomycim
- Trimethoprim-sulfamethoxazole
Frequently Asked Questions
Q1. How Are Gram-Negative Bacteria Treated?
Gram-negative bacteria are treated through the use of antibiotics. That’s why these have high resistance to antibiotics and are one of the world’s most serious public health problems. The cell membrane of gram-negative bacteria is thin and difficult to penetrate.
Q2. What is endotoxin?
Endotoxins are lipopolysaccharides that have an outer leaflet of the outer membrane of most Gram-negative bacteria.
Q3. When do Gram-negative bacteria release endotoxin?
Endotoxins are released when the cell wall of bacteria is disturbed.
Q4. What is the composition of lipopolysaccharides?
Lipopolysaccharides have three parts.
1. Lipid A backbone – Lipid A is a phosphorylated disaccharide. Long, hydrophobic fatty acid chains are attached to it. Lipid A anchors the lipopolysaccharides into the outer membrane. It is also known as endotoxin and stimulates a potent host inflammatory response.
2. Core oligosaccharide – The core oligosaccharide connects lipid A to the O antigen side-chain. Its composition differs between bacterial species.
3. O antigen side-chain – The O antigen is a repeating polysaccharide that projects from the surface of the bacterial cell and varies in length from 1 to 60 repeats. It is the antigenic portion of the molecule and is responsible for the serogroup classification of gram-negative bacteria.
Q5. What is the periplasmic space?
Periplasmic space is a space between the cytoplasmic membrane and the outer membrane. It is also called as periplasm. It is a multipurpose compartment that is separate from the cytoplasm.
The periplasmic space also have structural elements and some important environmental sensing modules. It allows complex nanomachines to span the cell envelope.
The distance between two membranes is much critical for sensing outer membrane damage.
Q6. What are the examples of gram-negative bacteria?
Hemophilis, Bordetella, Legionella, Neisseria, Salmonella, E.coli, and Campylobacter are some examples of gram-negative bacteria.
Q7. Is E.coli a gram-negative bacteria?
Yes, E.coli is a negative bacteria. It belongs to enteric straight facultative rods.
Q8. What is the importance of antibiotics in gram-negative bacteria?
Antibiotics are key weapons to combat infections because of gram-negative bacteria in modern medicine.
Millions of patients infected with Gram-negative bacteria have been cured and saved with these medicines.
But an extensive use of antibiotics have developed resistancce to common antimicrobial therapies.
It is compulsory to treat gram-negative bacterial infection. If not treated, it can lead to serious problems even death.
Q9. What are the symptoms of gram-negative bacteria?
Symptoms of gram-negative bacteria mainly depend on the site of the infection. Fever is the most common sign.
Q10. What are the most frequent multiple drug resistant (MDR) microorganisms?
Remember the word “ESKAPE” to remember that these are the most frequent microorganisms with multiple drug resistant (MDR).
E = Enterococcus faecium
S = Staphylococcus aureus
K = Klebsiella pneumoniae
A = Acinetobacter baumannii
P = Pseudomonas aeruginosa
E = Enterobacter spp
References
- Jane E. Sykes, Chapter 36 – Gram-negative Bacterial Infections, 2014, Pages 355-363, ISBN 9781437707953, https://doi.org/10.1016/B978-1-4377-0795-3.00036-3.
- Lemaître, Nadine et al. “Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC.” mBio vol. 8,4 e00674-17. 25 Jul. 2017, doi:10.1128/mBio.00674-17
- Lutz, R. (2020, December 19). Gram-Negative Infections Successfully Treated with Ceftazidime-Avibactam. Contagion Live. https://www.contagionlive.com/view/gram-negative-infections-treated-ceftazidime-avibactam
- Bassetti, M. (2011, March 22). New treatment options against gram-negative organisms – Critical Care. BioMed Central. https://ccforum.biomedcentral.com/articles/10.1186/cc9997