Pathogenic Gram-Negative Cocci and Bacilli: Structure, Physiology, and Clinical Relevance

Pathogenic Gram-Negative Bacteria

Overview and Clinical Importance

Gram-negative bacteria represent the largest group of human bacterial pathogens, primarily due to the presence of lipid A (endotoxin) in their outer membrane. This component is responsible for many of the toxic effects associated with Gram-negative infections, including fever, inflammation, shock, and disseminated intravascular coagulation (DIC). Most Gram-negative bacteria that breach the skin or mucous membranes, grow at 37°C, and evade the immune system can cause disease in humans.

• Lipid A (Endotoxin): Triggers immune responses such as fever, vasodilation, inflammation, shock, and DIC.

• Clinical Relevance: Infections can rapidly become life-threatening due to these systemic effects.

Pathogenic Gram-Negative Cocci: Neisseria

Structure and Physiology

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, which distinguishes them from many other Gram-negative pathogens. Pathogenic strains possess fimbriae, a polysaccharide capsule, and a cell wall containing lipid A.

• Key Pathogenic Species: N. gonorrhoeae and N. meningitidis

• Virulence Factors: Fimbriae, capsule, and endotoxin (lipid A)

Neisseria gonorrhoeae (The Gonococcus)

This species causes gonorrhea, a sexually transmitted disease that occurs only in humans. The risk of infection increases with the number of sexual encounters, and most cases in the United States occur in adolescents. Gonorrhea is more common in females than in males.

• Transmission: Sexual contact

• Clinical Features: Urethritis, cervicitis, pelvic inflammatory disease, and neonatal conjunctivitis

Neisseria meningitidis (The Meningococcus)

N. meningitidis is the most common cause of meningitis in individuals under 20 years of age. It can be part of the normal microbiota of the upper respiratory tract and is transmitted by respiratory droplets, especially among people living in close contact. Meningitis can cause death within hours of symptom onset, and meningococcal septicemia is also life-threatening.

• Transmission: Respiratory droplets

• Clinical Features: Meningitis, septicemia, petechiae (skin lesions)

Pathogenic Gram-Negative, Facultatively Anaerobic Bacilli

Families and Diagnostic Features

Two main families contain most human pathogens: Enterobacteriaceae and Pasteurellaceae. The oxidase test is used to distinguish between these families. These bacteria are important causes of healthcare-associated infections.

• Enterobacteriaceae: Intestinal microbiota, ubiquitous in water, soil, and decaying vegetation

• Pasteurellaceae: Includes genera such as Haemophilus

Structure and Physiology of Enterobacteriaceae

Members of the Enterobacteriaceae family are motile bacilli and coccobacilli that reduce nitrate to nitrite and ferment glucose. They grow best in aerobic environments and are distinguished by biochemical properties, motility, and colony characteristics.

• Motility: Most are motile with peritrichous flagella

• Biochemical Tests: Used for species identification

Classification of Pathogenic Enterobacteriaceae

Pathogenic Enterobacteriaceae are classified into three groups:

• Coliforms: Rapidly ferment lactose; normal microbiota but may be opportunistic pathogens

• Noncoliform opportunists: Do not ferment lactose

• True pathogens: Always pathogenic due to numerous virulence factors

Antigens and Virulence Factors

Enteric bacteria possess various antigens and virulence factors, including fimbriae, exotoxins, adhesins, and capsules. These factors contribute to their ability to cause disease.

• Type III Secretion System: Injects proteins into host cells to inhibit phagocytosis and manipulate host cell functions

• Capsule: Protects against phagocytosis

• Fimbriae and Adhesins: Facilitate attachment to host tissues

Coliform Opportunistic Enterobacteriaceae

Coliforms are aerobic or facultatively anaerobic, Gram-negative, rod-shaped bacteria that ferment lactose to form gas. They are commonly found in soil, plants, and the intestines of animals and humans. The presence of coliforms in water indicates contamination and poor sewage treatment.

• Example: Escherichia coli is the most common and important coliform.

Escherichia coli

• Virulence: Virulent strains have plasmids encoding fimbriae, adhesins, and exotoxins.

• Diseases: Gastroenteritis (diarrhea, cramps, nausea, vomiting), pediatric diarrhea, and hemolytic uremic syndrome (E. coli O157:H7).

• Transmission: Contaminated food (e.g., undercooked beef, milk, fruit juice)

Klebsiella

Klebsiella species are found in the digestive and respiratory systems. Their capsule protects them from phagocytosis. K. pneumoniae is the most commonly isolated pathogenic species, causing pneumonia, bacteremia, meningitis, wound infections, and UTIs.

Serratia

Serratia produces a red pigment at room temperature and can grow on hospital supplies, causing life-threatening infections in immunocompromised patients. It is frequently resistant to antimicrobial drugs.

Proteus

Proteus mirabilis is associated with urinary tract infections, especially in patients with long-term catheters. It can induce kidney stones and is resistant to many antimicrobial drugs.

Truly Pathogenic Enterobacteriaceae

This group includes Salmonella, Shigella, and Yersinia. They are almost always pathogenic due to their virulence factors, including type III secretion systems, which inhibit phagocytosis, rearrange host cytoskeletons, and induce apoptosis.

• Salmonella: Causes salmonellosis and typhoid fever; transmitted via contaminated food, especially poultry and eggs.

• Shigella: Causes shigellosis (severe dysentery); spread by contaminated hands or food; produces Shiga toxin.

• Yersinia: Includes Y. pestis, the causative agent of plague; rapid diagnosis and treatment are critical.

The Pasteurellaceae Family

Haemophilus

Haemophilus species are small, pleomorphic bacilli that require heme and NAD+ for growth. They colonize mucous membranes and can cause opportunistic infections. H. influenzae type b (Hib) was a common cause of meningitis before the introduction of the Hib vaccine.

• Diseases: Meningitis, conjunctivitis, sinusitis, dental abscesses

• Prevention: Hib vaccine

Pathogenic Gram-Negative, Aerobic Bacilli

Brucella

Brucella melitensis causes brucellosis, often a mild or asymptomatic disease in humans. Infection occurs through contact with contaminated dairy products or animal parts. The disease is characterized by fluctuating fever.

• Prevention: Vaccination of domesticated animals

Bordetella

Bordetella pertussis is the causative agent of pertussis (whooping cough), primarily affecting children. The disease is mediated by adhesins and toxins, including pertussis toxin, adenylate cyclase toxin, dermonecrotic toxin, and tracheal cytotoxin. The bacteria multiply in the epithelial cells of the respiratory tract.

• Stages: Incubation, catarrhal, paroxysmal, and convalescent

Pseudomonads

Pseudomonads are aerobic bacilli found in soil, decaying matter, and moist environments. Pseudomonas aeruginosa is an opportunistic pathogen, especially problematic in hospitals and for immunocompromised patients. It can infect almost any organ and is known for its resistance to drugs and ability to form biofilms.

• Virulence Factors: Fimbriae, adhesins, capsule, toxins, enzymes

• Clinical Relevance: Infections in burn patients, cystic fibrosis patients, and immunocompromised individuals

Francisella

Francisella tularensis is a nonmotile, strictly aerobic coccobacillus and an intracellular parasite of animals and amoebae. It has a diverse range of hosts, with reservoirs including rabbits, muskrats, and ticks in the United States.

Legionella

Legionella pneumophila is an aerobic, pleomorphic bacterium that inhabits water sources. Humans acquire infection by inhaling aerosols from contaminated water. Legionnaires’ disease results in pneumonia and can be fatal, especially in immunocompromised individuals.