Gram-Negative Bacteria

Overview and Clinical Importance

Gram-negative bacteria are a major group of human pathogens, characterized by their cell wall structure and ability to evade the immune system. Many species can breach skin or mucous membranes, grow at body temperature (37°C), and cause disease.

• Lipid A (Endotoxin): A component of the Gram-negative bacterial cell wall, responsible for triggering fever, vasodilation, inflammation, shock, and disseminated intravascular coagulation (DIC).

• Largest group of human bacterial pathogens: Due in part to the effects of lipid A.

Potential Effects of Lipid A (Endotoxin)

Lipid A initiates a cascade of immune and inflammatory responses.

• Leukocytes release cytokines (e.g., TNF-α, IL-1, IL-6, IL-8)

• Platelet activating factor (PAF) and blood-clotting reactions can lead to DIC

• Complement activation (C3a, C5a) leads to inflammation and shock

• Clinical outcomes: fever, shock, DIC, and inflammation

Organization of Pathogenic Gram-Negative Organisms

Classification by Morphology and Metabolism

• Gram-negative, oxidase positive cocci: Neisseria gonorrhoeae, Neisseria meningitidis

• Gram-negative, oxidase positive bacilli: Bordetella pertussis, Brucella, Bartonella, Pseudomonas spp.

• Facultative anaerobes (Pasteurellaceae): Pasteurella multocida, Haemophilus influenzae type B

Pathogenic Gram-Negative Cocci: Neisseria

General Features

Neisseria is the only genus of Gram-negative cocci that regularly causes disease in humans. These bacteria are aerobic, nonmotile, and typically arranged as diplococci. They are oxidase positive and possess virulence factors such as fimbriae and a polysaccharide capsule.

• Cell wall contains lipid A

• Pathogenic species: N. gonorrhoeae, N. meningitidis

Neisseria gonorrhoeae

Pathogenesis, Epidemiology, and Disease

• Adheres to genital, urinary, and digestive tract epithelium

• Evades immune system by secreting protease that cleaves secretory IgA in mucus

• Survives and multiplies within neutrophils; can be transported to deeper tissues

• Often asymptomatic in women; extremely painful in men

Incidence and Transmission

• Only occurs in humans; sexually transmitted

• Most cases in adolescents; more common in females

• Incidence has declined over decades

Clinical Manifestations

• Men: Painful urination, pus-filled discharge

• Women: Often asymptomatic, can infect cervix, uterus, and Fallopian tubes; may trigger pelvic inflammatory disease, ectopic pregnancy, or sterility

• Infections outside reproductive tract: proctitis, pharyngitis, gingivitis

• Newborns: Infection of cornea or respiratory tract during childbirth

Diagnosis, Treatment, and Prevention

• Diagnosis: Genetic probes for asymptomatic cases; Gram-negative diplococci in pus

• Treatment: Broad-spectrum intramuscular cephalosporins (e.g., ceftriaxone) plus azithromycin or doxycycline; resistance to penicillin, tetracycline, erythromycin, and aminoglycosides is common

• Prevention: Eye infections in newborns prevented with antimicrobials; rapid antigenic variation precludes vaccine; sexual abstinence, monogamy, and condom use recommended

Neisseria meningitidis

Pathogenesis, Epidemiology, and Disease

• Polysaccharide capsule resists lytic enzymes of host phagocytes

• Survives and reproduces within macrophages and neutrophils

• Causes life-threatening disease when invading blood or CSF

• Most damage from "blebbing" or shedding of outer membrane, resulting in DIC

• Petechiae (small hemorrhages) start on trunk and extremities; may coalesce into necrotic black regions

• Meningitis can cause death within hours of symptom onset

Incidence and Transmission

• Most common cause of meningitis in children and adults under 20

• Incidence in US: 0.3 cases per 100,000 population

• Normal microbiota in upper respiratory tract of ~40% healthy people

• Transmitted by respiratory droplets among people in close contact

• Symptoms: abrupt onset sore throat, fever, headache, stiff neck, vomiting, convulsions, rapid progression to death

• Two serogroups are basis for available vaccines

Diagnosis, Treatment, and Prevention

• Diagnosis: Rapid diagnosis critical; Gram-negative diplococci in CNS phagocytes (via spinal tap)

• Treatment: Immediate administration of semisynthetic cephalosporins (e.g., ceftriaxone or cefotaxime) reduces fatality to <10%; untreated cases nearly always fatal

• Prevention: Asymptomatic carriers make eradication unlikely; CDC recommends vaccination

Pathogenic Gram-Negative Bacilli: Bordetella pertussis

Pathogenesis, Epidemiology, and Disease

Bordetella pertussis is a small, aerobic, nonmotile coccobacillus that causes pertussis (whooping cough), primarily in children. Disease is mediated by adhesins and toxins.

• Virulence factors: Pertussis toxin, adenylate cyclase toxin, dermonecrotic toxin, tracheal cytotoxin

• Bacteria inhaled in aerosols multiply in epithelial cells

• Adhesion facilitated by filamentous hemagglutinin

Virulence Factors in Action

• Adhesion: Filamentous hemagglutinin (FH) binds glycoproteins on neutrophil cell membrane

• Immune Evasion: Cells survive in phagocytes; pertussis toxin increases FH receptor production; ACT inhibits leukocyte movement and killing

• Disruption of Cell Function: Pertussis toxin increases mucus production; ACT increases mucus; tracheal cytotoxin inhibits ciliary escalator

• Host Cell Death: Tracheal cytotoxin expels ciliary cells; dermonecrotic toxin causes vessel constriction and hemorrhage

Disease Phases for Pertussis

Complications by Age Group

• Babies and children: apnea, pneumonia, convulsions, encephalopathy, death

• Teens and adults: pneumonia, less severe complications

Diagnosis, Treatment, and Prevention

• Diagnosis: Clinical symptoms usually diagnostic

• Treatment: Primarily supportive

• Prevention: Immunization with DTaP (children <7), Tdap (older children/adults); CDC recommends vaccination for all ages

Whole-cell vs. Acellular Pertussis Vaccines

• Whole-cell: Inactivated bacteria with many antigens, including endotoxins; broad immunity but more side effects

• Acellular: Contains only a few antigens (e.g., FHA, pertactin, fimbriae, weakened pertussis toxin); fewer side effects

Summary Table: Key Pathogenic Gram-Negative Bacteria

Additional info: These notes cover the structure, pathogenesis, clinical features, and prevention of major Gram-negative cocci and bacilli, focusing on Neisseria and Bordetella. For exam preparation, students should understand the mechanisms of immune evasion, the role of endotoxins, and the rationale for vaccination strategies.