Chapter 20: The Gram-Negative Bacilli of Medical Importance

Gram-Negative Bacilli of Medical Importance

Overview

This chapter covers the medically significant Gram-negative bacilli, focusing on their classification, pathogenicity, and clinical relevance. These bacteria are diverse, inhabit various environments, and include both true pathogens and opportunists. Their outer membrane contains lipopolysaccharide (LPS), which acts as an endotoxin and contributes to their virulence.

Aerobic Gram-Negative Nonenteric Bacilli

General Characteristics

• Non-spore-forming rods found in diverse habitats: intestines, zoonotic reservoirs, respiratory tract, soil, and water.

• Most are not medically important, but some are true pathogens or opportunists.

• All possess an outer membrane LPS (endotoxin).

Key Genera:

• Pseudomonas and Burkholderia – opportunistic pathogens

• Brucella and Francisella – zoonotic pathogens

• Bordetella and Legionella – mainly human pathogens

Classification of Gram-Negative Pathogens

Table: Major Groups of Gram-Negative Rods

Group	Representative Genera	Key Features
Aerobes (do not ferment carbohydrates)	Pseudomonas, Burkholderia, Bordetella, Francisella, Alcaligenes	Oxidase positive, obligate aerobes
Facultative anaerobes (ferment carbohydrates)	Escherichia, Klebsiella, Citrobacter, Enterobacter	Lactose fermenters
Non-lactose fermenters, oxidase-negative	Salmonella, Shigella, Proteus, Providencia, Morganella, Hafnia, Edwardsiella, Serratia, Yersinia	Do not ferment lactose, oxidase negative
Non-lactose fermenters, oxidase-positive	Haemophilus, Pasteurella	Oxidase positive
Obligate anaerobes	Bacteroides	Anaerobic metabolism

Systems Profile: Pathogenic Gram-Negative Bacilli

Table: Clinical Manifestations by Organ System

Organism	Skin/Skeletal	Nervous/Muscle	Cardiovascular/Lymphatic/Systemic	Gastrointestinal	Respiratory	Urogenital
Pseudomonas aeruginosa	Complication of burns, skin rashes	Corneal ulcers, meningitis	Endocarditis		Complication of cystic fibrosis	Urinary tract infections
Bordetella pertussis					Whooping cough
Legionella spp.				Acute diarrhea	1. Pneumonia 2. Pontiac fever
Escherichia coli				Acute diarrhea, colitis		Urinary tract infections, hemolytic uremic syndrome
Salmonella typhi			Septicemia	Typhoid fever
Shigella spp.		Neuron damage		Acute diarrhea and bacillary dysentery
Yersinia pestis			Bubonic plague		Pneumonic plague

Pseudomonas: The Pseudomonads

General Features

• Small, Gram-negative rods with a single polar flagellum

• Free-living in soil, sea water, fresh water; colonize plants and animals

• Important decomposers and bioremediators

• Frequent contaminants in homes and clinical settings

• Use aerobic respiration; do not ferment carbohydrates

• Produce oxidase and catalase; many produce water-soluble pigments

Pseudomonas aeruginosa

• Common inhabitant of soil and water; intestinal resident in 10% of normal people

• Resistant to soaps, dyes, quaternary ammonium disinfectants, drugs, and drying

• Frequent contaminant of ventilators, IV solutions, anesthesia equipment

• Opportunistic pathogen; common cause of nosocomial infections in hosts with burns, neoplastic disease, cystic fibrosis

• Complications: pneumonia, UTI, abscesses, otitis, corneal disease, endocarditis, meningitis, bronchopneumonia

• Characteristic grapelike odor and greenish-blue pigment (pyocyanin)

• Multidrug resistant

Related Gram-Negative Aerobic Rods

Genera Burkholderia and Stenotrophomonas

• Similar to pseudomonads; wide variety of habitats in soil, water, and related environments

• Obligate aerobes; do not ferment sugars; motile, oxidase positive; opportunistic

Burkholderia cepacia

• Active in biodegradation of various substances

• Opportunistic agent in respiratory tract, urinary tract, and occasionally skin infections; drug resistant

Burkholderia pseudomallei

• Acquired through penetrating injury or inhalation from environmental reservoir

• Causes wound infections, bronchitis, pneumonia, septicemia

Stenotrophomonas maltophilia

• Natural habitat: fresh water, soil, plant roots, human fecal microbiota, domestic animals

• Clinical contaminant of disinfectants, dialysis/respiratory equipment, water dispensers, catheters (forms biofilms)

• Infections in cancer patients and those with invasive devices

• Highly drug-resistant; treated with trimethoprim and sulfamethoxazole

Brucella and Brucellosis

• Tiny Gram-negative coccobacilli; two species: Brucella abortus (cattle), Brucella suis (pigs)

• Causes brucellosis (malta fever, undulant fever, Bang disease) – zoonosis transmitted from infected animals

• Fluctuating fever pattern (weeks to a year)

• Treated with doxycycline or streptomycin; animal vaccine available

• Potential bioweapon

Francisella tularensis and Tularemia

• Causes tularemia, a zoonotic disease of mammals (especially rabbits) in the northern hemisphere

• Transmitted by contact with infected animals, water, dust, or vector bites (ticks, flies, mosquitoes)

• Symptoms: headache, backache, fever, chills, malaise, weakness, ulcerative skin lesions, swollen lymph glands, conjunctivitis, sore throat, intestinal disruption

• 10% death rate in systemic/pulmonic forms (treatable with gentamicin or streptomycin)

• Intracellular persistence can lead to relapse; no vaccine available; highly infectious; potential bioterrorism agent

Bordetella pertussis and Pertussis (Whooping Cough)

• Minute, encapsulated coccobacillus

• Causes pertussis (whooping cough), an acute respiratory syndrome, especially severe in infants

• Reservoir: apparently healthy carriers; transmission by direct contact or inhalation of aerosols

Virulence Factors

• Receptors for ciliated respiratory epithelial cells

• Toxins that destroy/dislodge ciliated cells, leading to mucus buildup and airway blockage

• Vaccine: DTaP (acellular, with toxoid and other antigens)

Genus Alcaligenes

• Primarily inhabit soil and water; may become part of normal microbiota

• Alcaligenes faecalis is the most common clinical species, isolated from feces, sputum, urine

• Occasionally causes opportunistic infections: pneumonia, septicemia, meningitis

Legionella pneumophila and Legionellosis

• Widely distributed in water, often associated with amoebas

• Outbreak in 1976 (Legionnaires’ disease); also causes Pontiac fever

• Prevalent in males over 50; nosocomial in elderly; not contagious

• Symptoms: fever, cough, diarrhea, abdominal pain; pneumonia fatality rate 15-25% (Legionnaires’ disease)

• Treatment: levofloxacin or azithromycin

Family Enterobacteriaceae

General Features

• Large family of small, non-spore-forming Gram-negative rods

• Inhabit soil, water, decaying matter, and large bowel of animals

• Most frequent cause of diarrhea via enterotoxins

• Account for ~30% of nosocomial infections (with Pseudomonas and Acinetobacter)

Key Characteristics

• Glucose fermentation

• Nitrate reduction

• Oxidase-negative

• Flagella (in most)

• Regular, straight rods

Divided into:

• Coliforms (lactose fermenters)

• Non-coliforms (non-lactose fermenters)

Enrichment, selective, and differential media are used for screening.

Table: IMViC Tests for Differentiating Common Opportunistic Enterics

Genus	Indole	Methyl Red	Voges-Proskauer	Citrate
Escherichia	+	+	–	–
Citrobacter	+	+	–	+
Klebsiella/Enterobacter	+/–	–	+	+
Serratia	V*	–	+	+
Proteus	+	+	–	+
Providencia	+	+	–	+
Pseudomonas	–	–	–	V*

*V = Species Variable

Antigenic Structures and Virulence Factors

• H antigen: flagellar antigen

• K antigen: capsule and/or fimbrial antigen

• O antigen: somatic or cell wall antigen (all have O; implicated in endotoxic shock)

• Virulence also linked to endotoxins, exotoxins, capsules, fimbriae, and attachment molecules

Escherichia coli: Most Prevalent Enteric Bacillus

• Most common aerobic, non-fastidious bacterium in the gut; 150 strains

• Some strains acquire virulence via plasmid transfer; others are opportunists

Pathogenic Strains (Pathotypes)

• Enterohemorrhagic E. coli (EHEC): hemorrhagic colitis, hemolytic uremic syndrome, kidney damage

• Enterotoxigenic E. coli (ETEC): severe diarrhea due to heat-labile and heat-stable toxins; has fimbriae

• Enteroinvasive E. coli (EIEC): inflammatory disease of the large intestine

• Enteropathogenic E. coli (EPEC): linked to infantile diarrhea

• Enteroaggregative E. coli (EAEC): pediatric diarrhea

• Diffusely adherent E. coli (DAEC): minor cause of pediatric diarrhea

Clinical Relevance

• Pathogenic strains are frequent agents of infantile diarrhea (major cause of infant mortality)

• Cause ~70% of traveler's diarrhea and 50-80% of UTIs

• Oral antimicrobics may be effective early; bismuth salicylate (Pepto-Bismol) counteracts enterotoxin

Role in Food Infections

• O157:H7 (EHEC): associated with foodborne outbreaks (e.g., undercooked beef); produces shiga toxin

• Toxin disrupts host protein synthesis, leading to cell death and intestinal shedding

• USDA requires warning labels on fresh meat/poultry for safe handling

Other Coliforms

• Klebsiella pneumoniae: large capsule, nosocomial pneumonia, meningitis, bacteremia, wound infections, UTIs

• Enterobacter spp.: UTIs, surgical wounds

• Citrobacter spp.: UTIs, bacteremia

• Serratia marcescens: red pigment, pneumonia, burn/wound infections, septicemia, meningitis

Carbapenem-Resistant Enterobacteriaceae (CRE)

• Includes Klebsiella, Enterobacter, some E. coli; nosocomial opportunists

• Resistance via enzymes: KPC, NDM, VIM

• Risk factors: indwelling devices (ventilators, catheters, endoscopes)

Noncoliform Lactose-Negative Enterics

• Opportunists: Proteus, Morganella, Providencia

• True pathogens: Salmonella, Shigella

Proteus and Relatives

• Harmless saprobes in soil, sewage, water, and as commensals

• Proteus spp.: swarming growth on agar, involved in UTIs, wound infections, pneumonia, septicemia, infant diarrhea

• Morganella morganii and Providencia spp.: similar infections

True Enteric Pathogens: Salmonella and Shigella

• Well-developed virulence factors; not normal human microbiota

• Cause gastrointestinal and systemic diseases

Typhoid Fever and Salmonelloses

• Salmonella enterica (multiple subspecies and serotypes)

• Flagellated, survive outside host, resistant to bile/dyes

• Typhoid fever: ingestion of contaminated food/water; chronic carriers may shed from gallbladder

• Invasive diarrhea, septicemia; treated with ciprofloxacin or ceftriaxone; two vaccines available

Shigella and Bacillary Dysentery

• Etiologic agents: S. dysenteriae, S. sonnei, S. flexneri, S. boydii

• Invades large intestine villi, causes inflammatory response, does not invade blood

• Symptoms: fever, cramps, frequent watery stool with mucus/blood

• Treatment: fluid replacement, ciprofloxacin, sulfamethoxazole-trimethoprim

The Enteric Yersinia Pathogens

• Yersinia enterocolitica: from animals, fish, vegetables, water; invades small intestine, can mimic appendicitis

• Y. pseudotuberculosis: similar infection, more lymph node involvement

Yersinia pestis and Plague

• Nonenteric, tiny Gram-negative rod, bipolar staining, capsule

• Virulence: capsule, envelope proteins, coagulase, endotoxin, murine toxin

• Transmitted via fleas from rodents; causes bubonic, septicemic, and pneumonic plague

• Diagnosis: clinical history, lab findings from buboes; treatment: ciprofloxacin; vaccine available

Oxidase-Positive Nonenteric Pathogens: Family Pasteurellaceae

• Pasteurella: zoonotic, normal flora in animals, causes abscesses after animal bites/scratches; treat with amoxicillin or ciprofloxacin

• Haemophilus influenzae: fastidious, requires chocolate agar; causes meningitis, bacteremia, pneumonia; vaccine available for type b

• Haemophilus ducreyi: agent of chancroid STD; treat with azithromycin

• H. parainfluenzae: normal oral/nasopharyngeal flora, can cause endocarditis

Key Concepts and Review Questions

• Main reservoir for Pseudomonas aeruginosa: Soil and water

• Enterics: Some are normal flora, some release endotoxin, some release enterotoxins (all are true)

• Bubo of bubonic plague: Enlarged (swollen) lymph node