Chapter 20

Pathogenic Gram-Negative Cocci and Bacilli

Gram-Negative Bacteria

• Neisseria, Enterobacteriaceae (E.coli, Klebsiella, Serratia, Proteus, Salmonella, Shigella, Yersinia)

• Pasteurella, Haemophilus, Brucella, Bordetella

• Pseudomonas, Moraxella, Francisella, Legionella

• Bacteroides

Gram-Negative Bacteria

• Constitute the largest group of human pathogens

• Due in part to the presence of lipid A in the bacterial cell wall

• Triggers fever, vasodilation, inflammation, shock, and disseminated intravascular coagulation (blood clots within blood vessels)

• Almost every Gram-negative bacterium that can breach the skin or mucous membranes, grow at 37°C, and evade the immune system can cause disease and death in humans

Neisseria

• 1879 - Albert Neisser identifies Neisseria gonorrhoeae, the pathogen that causes gonorrhea. He may be the first to attribute a chronic disease to a microbe.

Neisseria

• Only genus of Gram-negative cocci that regularly causes diseases in humans

• Nonmotile, aerobic bacteria often arranged as diplococci

• Distinguished from many other Gram-negative pathogens by being oxidase positive

• 2 species are pathogenic to humans

• The gonococcus, N. gonorrhoeae

• The meningococcus, N. meningitides

Neisseria gonorrhoeae

• Causes gonorrhea, a sexually transmitted disease

• Gonococci adhere to epithelial cells of the mucous membranes lining the genital, urinary, and digestive tracts of humans spreading to deeper tissue as they multiply

• Gonorrhea in men

• Usually symptomatic producing inflammation that causes painful urination and pus-filled discharge

Neisseria gonorrhoeae

• Gonorrhea in women

• Often asymptomatic

• Can infect the cervix and other parts of the uterus, including the Fallopian tubes

• Can result in pelvic inflammatory disease (PID)

• Can result in ectopic pregnancy or sterility

• Gonococcal infection of children can occur during childbirth producing inflammation of the cornea and sometimes blindness

Diagnosis, Treatment, and Prevention

• Diagnosis

• Gonorrhea in men can be identified by the presence of Gram-negative diplococci in pus from an inflamed penis

• Asymptomatic cases can identified with commercially available genetic probes

• Treatment

• Complicated due to resistant gonococcal strains

• Broad-spectrum antimicrobial drugs are often used

• Prevention

• Most effective prevention is sexual abstinence

Neisseria meningitidis

• Humans are the only natural carrier of N. meningitides

• Can be member of the normal microbiota of the upper respiratory tract

• Causes life-threatening disease when the bacteria invade the blood or cerebrospinal fluid

• Most common cause of meningitis in individuals under 20

• Respiratory droplets transmit the bacteria among people living in close contact, especially students living in dormitories

Neisseria meningitidis

• Meningococcal meningitis can result in death as early as 6 hours after initial symptoms

• Meningococcal septicemia, blood poisoning, can also be life threatening

• Can produce blood coagulation and the formation of minute hemorrhagic lesions

Diagnosis, Treatment, and Prevention

• Diagnosis

• Presence of Gram-negative diplococci in phagocytes of the central nervous system

• Treatment

• Penicillin, administered intravenously, is the drug of choice

• Prevention

• Eradication is unlikely due to the presence of asymptomatic carriers

Enterobacteriaceae

• Members of the intestinal microbiota of most animals and humans

• Ubiquitous in water, soil, and decaying vegetation

• Enteric bacteria are the most common Gram-negative pathogens of humans

• Coccobacilli or bacilli

Diagnosis, Treatment, and Prevention

• Diagnosis

• Enterobacteriaceae are cultured using selective and differential media

• Commercially available biochemical tests can rapidly identify enteric bacteria

• Treatment

• Treatment of diarrhea involves treating the symptoms with fluid and electrolyte replacement

• Antimicrobial drugs are not usually needed since diarrhea is self-limited

Diagnosis, Treatment, and Prevention

• Prevention

• Preventing enteric infections is almost impossible since they are a major component of the normal microbiota

• Good personal hygiene and proper sewage control are important in limiting the risk of infection

Enterobacteriaceae Classification

• Pathogenic Enterobacteriaceae are often classified into three groups

• Coliforms, which rapidly ferment lactose, are part of the normal microbiota, and may be opportunistic pathogens

• Noncoliform opportunists, which do not ferment lactose

• True pathogens

Coliform Opportunistic Enterobacteriaceae

• Aerobic or facultatively anaerobic, Gram-negative, rod-shaped bacteria

• Commonly found in soil, on plants, and on decaying vegetation

• Colonize the intestinal tracts of animals and humans

• Presence of coliforms in water is indicative of impure water and of poor sewage treatment

Escherichia coli

• The most common and important of the coliforms

• Virulent strains have genes located on virulence plasmids that allow the bacteria to colonize human tissue

• Gastroenteritis is the most common disease associated with E.coli

• Often mediated by exotoxins that produce the symptoms associated with gastroenteritis

• Most common cause of non-nosocomial urinary tract infections

Escherichia coli

• E.coli O157:H7 is the most prevalent strain of pathogenic E.coli in developed countries

• Causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome, a severe kidney disorder

• Most epidemics associated with undercooked ground beef or unpasteurized milk or juice

• Produces a Shiga-like toxin that aids in the virulence of the bacteria

Klebsiella

• Found in the digestive and respiratory systems of humans and animals

• Can cause opportunistic infections

• Produce a capsule that protect the bacteria from phagocytosis

• K.pneumoniae is the most commonly isolated pathogenic species

• Causes pneumonia

• May be involved in bacteremia, meningitis, wound infections, UTIs

Serratia

• Produce a red pigment when grown at room temperature

• Can grow on catheters, in saline solutions, and other hospital supplies

• Can cause life-threatening opportunistic infections in the urinary and respiratory tracts of immunocompromised patients

• Difficult to treat due to resistance to various antimicrobial drugs

Noncoliform Opportunistic Enterobacteriaceae

• Include a number of opportunistic pathogens

• Proteus

• Gram-negative, facultative anaerobe

• Proteus mirabilis is the most common species associated with human disease

• Can cause urinary tract infections in patients with long-term urinary catheters

• Infection-induced kidney stones can develop

• Resistant to many antimicrobial drugs

Truly Pathogenic Enterobacteriaceae

• Important members of this group almost always pathogenic due to numerous virulence factors
All are lactose negative in sugar fermentation studies

Salmonella

• Gram-negative, motile, bacilli

• Found in the intestines and feces of most birds, reptiles, and mammals

• Most salmonella infections in humans are the result of consumption of food contaminated with animal feces

• Poultry and eggs are particularly common sources of Salmonella

• 2 important pathogens

• S.typhimurium-causes salmonellosis

• S.typhi-causes typhoid fever

The events of salmonellosis

Salmonella typhi

• Humans are the only host

• Causes typhoid fever

• Infection occurs via ingestion of food or water contaminated with sewage containing bacteria from carriers

• Bacteria can pass through the intestines into the bloodstream and into the liver, spleen, bone marrow, and gall bladder

• Bacteria from the gall bladder can reinfect the intestines, producing gastroenteritis and a recurrence of bacteremia

Salmonella typhi

• In some patients the bacteria ulcerate and perforate the intestinal wall causing peritonitis

• Treatment is through the use of antimicrobial drugs

• Vaccines are available to provide temporary protection to individuals traveling to areas where typhoid fever is endemic

Shigella

• Gram-negative, nonmotile bacteria

• Primarily a parasite of the digestive tract of humans

• Produce a diarrhea-inducing enterotoxin

• Cause a sever form of dysentery called shigellosis

Shigella

• 4 well-defined species

• S.boydii

• S.sonnei-most commonly isolated in industrialized nations

• S. flexneri-most commonly isolated in developing countries

• S.dysenteriae-produces a more serious disease than the other species

• Shigellosis is treated with fluid and electrolyte replacement

Yersinia

• Normal pathogens of animals

• 3 important species

• Y.enterocolitica

• Acquired via consumption of food or water contaminated with animal feces

• Causes inflammation of the intestinal tract

• Y.pseudotuberculosis

• Similar to Y.enterocolitica but produces a less severe intestinal inflammation

Yersinia

• Y.pestis

• Bubonic plague-characterized by high fever and swollen, painful lymph nodes called buboes

• Pneumonic plague-rapidly developing infection of the lungs

Diagnosis, Treatment, and Prevention

• Diagnosis and treatment must be rapid due to the fast progression and deadliness of the plague

• Diagnosis

• Characteristic symptoms are usually sufficient for diagnosis

• Treatment

• Many antibacterial drugs are effective against Yersinia

Pasteurellaceae

• Most are small, nonmotile, facultative anaerobes

• Require heme or cytochromes for growth = fastidious

Pasteurella

• Normal microbiota in the oral and nasopharyngeal cavities of animals such as cats and dogs

• Humans are typically infected via animal bites and scratches or via inhalation of aerosols from animals

• Most cases produce localized inflammation and swelling of the lymph nodes at the site of infection

• Diagnosis is by the identification of the bacteria in specimens collected from the patient

• Antibacterial drugs are an effective treatment

Haemophilus

• Small, pleomorphic bacilli

• Obligate parasites due to their requirement of heme and NAD⁺ for growth

• Colonize the mucous membranes of humans and some animals

Haemophilus influenzae

• Most strains have a polysaccharide capsule that resists phagocytosis and is used in classification of the bacteria

• H.influenzae type b is the most significant

• Was the most common form of meningitis in infants prior to the use of an effective vaccine

• Can cause a number of other diseases in young children

• Use of the Hib vaccine has eliminated much of the disease caused by H.influenzae b

• Other strains still cause a variety of diseases

Other Species of Haemophilus

• H.ducreyi

• Causes a sexually transmitted disease

• Results in the formation of a genital ulcer called a chancroid

• Often asymptomatic in women but in men the chancroid is often painful

• H.aphrophilus causes a rare type of endocarditis

• Other species primarily cause opportunistic infections

Brucella

• Small, nonmotile, aerobic coccobacilli

• Can infect animals or humans

• Causes brucellosis

• Often an asymptomatic or mild disease

• Illness is characterized by a fluctuating fever

• Humans become infected by coming in contact with contaminated dairy products or from infected animal parts

Bordetella

• Small, aerobic, nonmotile coccobacillus

• B. pertussis is the most important

• Causes pertussis, also called whopping cough

• Most cases of disease are in children

• Produce various adhesins and toxins, including pertussis toxin, that mediate the disease

• Bacteria are first inhaled in aerosols and multiply in epithelial cells

• Then progress through four stages of disease

Diagnosis, Treatment, and Prevention

• Diagnosis

• Symptoms of pertussis are usually diagnostic

• Treatment

• Primarily supportive

• Antibacterial drugs have little effect on the course of the disease

• Prevention

• Immunization with the DPT vaccine

• Cases in the United States have increased due to a refusal by some parents to have their children immunized

Pseudomonads

• Gram-negative, aerobic bacilli

• Ubiquitous in soil, decaying organic matter, and almost every moist environment

• Problematic in hospitals because they can be found in numerous locations

• Opportunistic pathogens

Pseudomonas aeruginosa

• Rarely part of the normal microbiota

• Opportunistic pathogen of immunocompromised patients

• Can colonize almost every organ and system and result in various diseases

• Often infects the lungs of cystic fibrosis patients

• The bacteria form a biofilm that protects them from phagocytosis

• Increases the likelihood of death in these patients

Pseudomonas aeruginosa

• Diagnosis can be difficult as the presence of bacteria may represent contamination of the sample

• Treatment is difficult because P. aeruginosa is resistant to many antibacterial drugs

Moraxella

• Aerobic, short, plump, bacilli

• Moraxella catarrhalis can cause opportunistic infections of the sinuses, bronchi, ears, and lungs

• Originally called Neisseria catarrhalis. Virginia Branham did extensive cell-wall and fatty acid analysis to distinguish this organism. Her work resulted in a new genus Branhamella.
Type species was B. catarrhalis.

Moraxella

• However, her work led others to do more work. Branhamella was found to really belong in the genus Moraxella.

• M. catarrhalis may cause clinical syndromes indistinguishable from those caused by gonococci, and so it is important to distinguish these organisms from one another. Many strains produce ß-lactamase

Francisella tularensis

• Nonmotile, strictly aerobic coccobacillus

• Found living in water as an intracellular parasite of animals

• Causes the zoonotic disease tuleremia

• Spread to humans occurs mainly through the bite of an infected tick or by contact with an infected animal

• The bacteria can spread through unbroken skin and mucous membranes, making it highly infectious

• Tuleremia produces symptoms common to other bacterial and viral diseases and may be misdiagnosed

Francisella Tularensis

• A vaccine is available to at risk individuals

• Preventing infection is done by avoiding the major reservoirs of the bacteria

Legionella pneumophila

• Aerobic, slender, pleomorphic bacteria

• Universal inhabitants of water

• Humans acquire the disease by inhaling the bacteria in aerosols from various water sources

• Intracellular parasites

• Causes Legionnaires’ disease

• Results in pneumonia

• Immunocompromised individuals are more susceptible

• Elimination of the bacteria is not feasible but reducing their number is a successful control measure

Pathogenic, Gram-Negative, Anaerobic Bacilli

• Anaerobic bacteria are the predominant microbiota of the gastrointestinal, urinary, reproductive, and lower respiratory tracts

• Important for human health

• Inhibit the growth of most pathogens, synthesize necessary vitamins, and aid in digestion of food

• Cause disease only when they are introduced into other parts of the body by trauma or surgery

Bacteroides

• Normal microbiota of the intestinal tract and the upper respiratory tract

• Bacteroides fragilis is the most important

• Can be involved in abdominal infections, genital infections in women, and wound infections of the skin