Gram-negative bacteria are characterized by their cell wall structure, which includes an outer membrane that contains lipopolysaccharides (LPS).
Typical size: 10μm and are often studied through laboratory techniques such as Gram staining.
List of Major Gram-Negative Bacteria and Associated Infectious Diseases
Escherichia coli
Salmonella enterica
Shigella spp.
Proteus mirabilis
Neisseria meningitidis
Neisseria gonorrhoeae
Haemophilus influenzae
Pseudomonas aeruginosa
Vibrio cholerae
Campylobacter jejuni
Helicobacter pylori
Endotoxins
Definition: Endotoxins are components of the outer membrane of Gram-negative bacteria, primarily lipopolysaccharides (LPS).
Characteristics:
LPS can be released into the extracellular environment during cell division or cell death.
The lipid component, referred to as lipid A, anchors LPS to the outer membrane and displays several important characteristics:
Conserved across Gram-negative bacteria
Responsible for the toxic properties of the bacteria
Triggers inflammation and fever responses in the immune system.
High concentrations of endotoxins can lead to an excessive inflammatory response that may result in toxic shock and disseminated intravascular coagulation (DIC), which is the formation of blood clots throughout the body.
Generally, these bacteria have a high LD50 (~0.24 mg/kg), indicating the lethal dose for 50% of a sample population.
Family Enterobacteriaceae
Definition: Family Enterobacteriaceae, also known as enteric bacteria, consists of members that are part of the gastrointestinal (GI) microbiota of various animals and humans.
Habitat: Found in water, soil, and decaying material.
Role in Humans:
Many are mutualistic or commensalistic, while others can be pathogenic or opportunistic pathogens.
Includes more than 60 genera, such as Citrobacter, Enterobacter, Klebsiella, Escherichia, Salmonella, Shigella, Proteus, Serratia, and Yersinia.
Characteristics:
Facultative anaerobes (can grow in both the presence and absence of oxygen).
Morphology: Bacilli or coccobacilli.
Coliforms (not a formal taxon): A subgroup of enteric bacteria that ferment lactose within 48 hours in the lab, often used as indicators of sanitary conditions.
Specific Pathogens and Their Diseases
Escherichia coli (E. coli)
General Information: Most strains are commensal or mutualistic, residing in the lower intestine of humans and many other endotherms.
Pathogenic Impact:
Pathogenic strains can cause gastrointestinal diseases as well as extraintestinal infections.
Transmission: Fecal-oral route is the most common transmission method.
Serotypes: About 190 serotypes identified based on major surface antigens:
Antigen O: part of LPS
Antigen H: flagellin
Antigen K: capsule
Antigen F: fimbriae
Enterotoxigenic E. coli (ETEC)
Common Name: Traveler's disease commonly found in underdeveloped countries.
Symptoms: Watery diarrhea, abdominal cramps, malaise, and low or no fever.
Mechanism:
Colonization via fimbrial adhesins that attach to enterocytes (cells of the small intestine wall).
Produces two enterotoxins (one heat-labile and one heat-stable), causing ionic imbalances in enterocytes, resulting in watery diarrhea.
Invasiveness: Non-invasive, usually confined to the intestinal lumen; disease is often mild and self-limiting.
Enteropathogenic E. coli (EPEC)
Characteristics: Can potentially be fatal. Does not produce toxins.
Symptoms: Fever, vomiting, diarrhea leading to severe dehydration.
Mechanism: Utilizes intimin (an adhesin protein) to attach to epithelial cells, inducing actin rearrangements that create a structure referred to as a pedestal.
Invasiveness: Moderately invasive; disease often linked to consumption of poorly washed vegetables or uncooked meats.
Enteroinvasive E. coli (EIEC)
Characteristics: Highly invasive, causing intracellular invasion of intestinal epithelial tissue.
Mechanism: Contains a large plasmid (pINV) for tissue penetration and survival.
Symptoms: Watery diarrhea with associated chills, cramps, malaise, and high fever (syndrome known as dysentery); disease is usually self-limiting.
Enterohemorrhagic E. coli (EHEC) / Shiga-toxin producing E. coli (STEC)
Characteristics: Involved in epidemics, particularly serotype O157:H7.
Mechanism: Produces verotoxin (shiga-like toxin) leading to damage of blood vessel endothelium cells.
Consequences: Can result in hemorrhagic colitis and hemolytic uremic syndrome (HUS), characterized by low RBC counts leading to kidney failure. Toxin is especially effective on small blood vessels.
Symptoms: Bloody diarrhea.
Uropathogenic E. coli (UPEC)
Characteristics: Causes 90% of urinary tract infections (UTIs).
Mechanism: Uses p-fimbriae to bind to urothelial cells and can form polysaccharide capsules leading to biofilm formation and recurrent UTIs resistant to antibiotics.
Neonatal Meningitis E. coli (NMEC)
Concern: Associated with maternal vaginal presence during childbirth, leading to infections.
Shigella spp.
General Information: Traditionally includes four species and numerous serotypes: S. dysenteriae, S. flexneri, S. boydii, S. sonnei.
Biological Classification: Current data suggests Shigella may be a species within the Escherichia genus.
Mechanism: Invades intestinal epithelial cells via inducing endocytosis; can escape phagocytosis, replicate, and cause tissue damage.
Symptoms: Produces bacillary dysentery (shigellosis), manifesting as cramping, fever, and watery diarrhea, potentially containing pus or blood.
Severe Cases: Can also develop HUS, with S. dysenteriae producing shiga toxin, similar in effects to E. coli O157:H7.
Salmonella spp.
General Information: Non-coliform enteric bacteria; two main species associated with human disease are S. enterica and S. bongori.
Infection Source: Human infections primarily derived from ingesting contaminated food (especially poultry and eggs). Reptile pets are also a risk factor.
Mechanism: Salmonella is motile and behaves as an intracellular pathogen, often involving pathogenicity islands for virulence.
Typhoid Fever
Infection: Caused by Salmonella enterica typhi, which infects only humans and has some asymptomatic carriers.
Symptoms: High fever, body aches, headaches, nausea, and potential rash.
Complications: Include intestinal ulceration, perforation, pneumonia, and disseminated disease.
Salmonellosis
Cause: Mainly Salmonella enterica enteritidis and S. typhimurium.
Mechanism: Penetrates intestinal epithelial cells, particularly M cells, leading to inflammation.
Symptoms: Fever, nausea, abdominal cramps, vomiting, headache, and diarrhea; disease is usually self-limiting.
Proteus mirabilis
Characteristics: Opportunistic pathogen, widely distributed and can alter phenotype based on media.
Mechanism: Capable of causing UTIs, especially in patients with long-term catheters.
Urease Production: Breaks down urea into ammonia, raising the pH of urine and potentially leading to kidney stones.
Antibiotic Resistance: Often develops resistance to multiple antibiotics; susceptibility tests are recommended.
Neisseria spp.
General Information: Aerobic, non-motile cocci.
Pathogenic Features:
Contains a polysaccharide capsule and lipo-oligosaccharide (LOS) instead of LPS.
Fimbriae present for adherence.
N. gonorrhoeae (gonococcus)
Infection: Causes gonorrhea, a sexually transmitted disease (STD), more frequent in females but with more severe symptoms in males.
Symptoms: Painful urination and purulent discharge; potential for pelvic inflammatory disease (PID) in females.
Complications: Can cause chronic issues, including infertility; multidrug resistant strains are prevalent.
N. meningitidis (meningococcus)
Infection: Causes meningococcal meningitis.
Mechanism: Survives in phagocytes, capable of “blebbing” to shed endotoxins into the environment.
Transmission: Common in crowded living arrangements; may carry asymptomatically.
Treatment: Responds well to intravenous penicillin and has a vaccine available.
Haemophilus influenzae
Characteristics: Facultative anaerobe and coccobacillus; requires heme to grow
Pathogenic Features: Obligate pathogen that evades phagocytosis via a polysaccharide capsule.
Diseases:
Meningitis: Symptoms include fever, headache, and confusion.
Pneumonia: Symptoms include fever, cough, and muscle pain.
Bacteremia: Symptoms include fever and confusion.
Resistance: Some strains are resistant due to beta-lactamases and modifications in PBP (penicillin-binding proteins).
Vaccination: Available since the 1990s.
Pseudomonas aeruginosa
Characteristics: Aerobic bacilli found in various environments and common in healthcare-associated infections.
Effects: Particularly affects immunocompromised patients and can cause unique infections such as hot-tub folliculitis.
Pathogenic Factors:
Produces fimbriae for adherence and biofilm formation.
Secretes extracellular enzymes like elastase, which can degrade various host elements.
Releases exotoxin A and exoenzyme S to inhibit host cell protein synthesis.
Contains efflux pumps to expel antibiotics.
Vibrio cholerae
Habitat: Found in estuary and marine ecosystems; slightly curved bacilli.
Transmission: Humans infected primarily through contaminated water.
Disease Caused: Cholera, characterized by profuse watery diarrhea leading to dehydration.
Virulence Factor: Cholera toxin, an A-B type toxin that disrupts intestinal electrolyte balance, leading to significant water loss.
Infection Source: Frequently found in birds and mammals; humans typically infected by contaminated poultry.
Disease Info: Most common cause of gastroenteritis; usually mild but can lead to Guillain-Barre syndrome.
Pathogenic Mechanism: Produces adhesins and toxins affecting intestinal cells; utilizes LPS as a PAMP to elicit an immune response.
Helicobacter pylori
Characteristics: Slightly helical, highly motile; transmitted via the fecal-oral route.
Impact: Colonizes stomach cells, producing urease leading to peptic ulcers characterized by symptoms such as stomach pain and bloating.
Historical Significance: Linked to peptic ulcers in 1982 by Dr. Robert Warren and Dr. Barry Marshall, who won a Nobel Prize for this discovery in 2005.
Disease Risk: Long-term H. pylori infections increase the risk of stomach cancer.
Virulence Factors: Include urease production to increase gastric pH, flagella for burrowing through mucus lining, and enzymes that inhibit phagocytic killing.
Key Figures
Figure 3.15: Illustrates cell lysis and crenation in cells lacking a cell wall under varying osmotic pressures.
Figure 15.8: Helicobacter pylori evading the epithelial cell layer in the stomach, causing peptic ulcers.