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Chapter 19

Pathogenic Gram-Positive Cocci and Bacilli

Gram-Positive Pathogens

• Stain purple when properly gram-stained

• Can be categorized into 2 major groups based on their DNA

• Low G + C organisms

• Genera of cocci-shaped organisms- Staphylococcus, Streptococcus, and Enterococcus

• Genera of bacilli-shaped organisms- Bacillus, Clostridium, and Listeria

• High G + C organisms

• Genera of bacilli-shaped organisms- Corynebacterium, Mycobacterium, Propionibacterium, Nocardia, and Actinomyces

Staphylococcus

• Normal members of every human’s microbiota

• Can be opportunistic pathogens

Structure and Physiology

• Gram-positive cocci, nonmotile, facultative anaerobes

• Cells occur in grapelike clusters because cells division occurs along different planes and the daughter cells remain attached to one another

• Salt-tolerant-allows them to tolerate the salt present on human skin

• Tolerant of desiccation-allows survival on environmental surfaces (fomites)

Structure and Physiology

• Three species are commonly associated with staphylococcal diseases in humans

• Staphylococcus aureus-The more virulent strain that can produce a variety of conditions depending on the site of infection

• Staphylococcus epidermidis-Normal microbiota of human skin that can cause opportunistic infections in immunocompromised patients or when introduced into the body

• Staphylococcus saprophyticus – a frequent cause of urinary tract infections, esp. in young women.

Pathogenicity

• “Staph’ infections result when staphylococci breach the body’s physical barriers

• Entry of only a few hundred bacteria can result in disease

• Pathogenicity results from 3 features

• Structures that enable it to evade phagocytosis

• Production of enzymes

• Production of toxins

Structural Defenses Against Phagocytosis

• Protein A coats the cell surface

• Interferes with humoral immune responses by binding to class G antibodies

• Inhibits the complement cascade

• Bound coagulase

• Converts the soluble blood protein fibrinogen in insoluble fibrin molecules that form blood clots

• Fibrin clots hide the bacteria from phagocytic cells

Structural Defenses Against Phagocytosis

• Synthesize loosely organized polysaccharide slime layers (often called capsules)

• Inhibit chemotaxis of and phagocytosis by leukocytes

• Facilitates attachment of Staphylococcus to artificial surfaces

Enzymes

• Cell-free coagulase

• Triggers blood clotting

• Hyaluronidase

• Breaks down hyaluronic acid, enabling the bacteria to spread between cells

• Staphylokinase

• Dissolves fibrin threads in blood clots, allowing S.aureus to free itself from clots

Enzymes

• Lipases

• Digest lipids, allowing staphylococcus to grow on the skin’s surface and in cutaneous oil glands

• b-lactamase

• Breaks down penicillin

• Allows the bacteria to survive treatment with b-lactam antimicrobial drugs

Toxins

• Staphylococcus aureus produces toxins more frequently than S.epidermidis

• Cytolytic toxins

• Disrupts the cytoplasmic membrane of a variety of cells

• Leukocidin can lyse leukocytes specifically

• Exfoliative toxins

• Causes the patient’s skin cells to separate from each other and slough off the body

Toxins

• Toxic-shock-syndrome toxin

• Causes toxic shock syndrome

• Enterotoxins

• Stimulate the intestinal muscle contractions, nausea, and intense vomiting associated with staphylococcal food poisoning

Staphylococcal Diseases

• 3 categories

• Noninvasive Disease

• Food poisoning from the ingestion of enterotoxin-contaminated food

• Cutaneous Disease

• Various skin conditions including scalded skin syndrome, impetigo, folliculitis, and furuncles

Staphylococcal Diseases

• Systemic Disease

• Toxic shock syndrome-TSS toxin is absorbed into the blood and causes shock

• Bacteremia-presence of bacteria in the blood

• Endocarditis-occurs when bacteria attack the lining of the heart

• Pneumonia-inflammation of the lungs in which the alveoli and bronchioles become filled with fluid

• Osteomyelitis-inflammation of the bone marrow and the surrounding bone

Diagnosis, Treatment, and Prevention

• Diagnosis

• Detection of Gram-positive bacteria in grapelike arrangements isolated from pus, blood, or other fluids

• Treatment

• Methicillin is the drug of choice to treat staphylococcal infections

• Is a semisynthetic form of penicillin and is not inactivated by b-lactamase

Diagnosis, Treatment, and Prevention

• Prevention

• Hand antisepsis is the most important measure in preventing nosocomial infections

• Also important is the proper cleansing of wounds and surgical openings, aseptic use of catheters or indwelling needles, an appropriate use of antiseptics

Streptococcus

• Gram-positive cocci, arranged in pairs or chains, that are facultative anaerobes

• Often categorized based on the Lancefield classification (Rebecca Lancefield 1895-1981)

• Divides the streptococci into serotype groups based on the bacteria’s antigens

• Lancefield groups A and B include the significant streptococcal pathogens of humans

Group A Streptococcus: Streptococcus pyogenes

• S. pyogenes forms white colonies surrounded by zone of beta-hemolysis on blood agar plates

• Pathogenic strains often form a capsule

• Group A streptococci generally only cause disease in the following situations:

• Normal microbiota are depleted

• Large inoculum enable the streptococci to establish themselves before antibodies are formed against them

• Specific immunity is impaired

Pathogenicity

• Structural components

• Protein M, which interferes with opsonization and lysis of the bacteria and a hyaluronic acid capsule, which acts to camouflage the bacteria

• Enzymes

• Streptokinases, deoxynucleases, and C5a peptidase all facilitate the spread of streptococci through tissues

• Pyrogenic toxins that stimulate macrophages and helper T cells to release cytokines

• Streptolysins lyse red blood cells, white blood cells, and platelets

Group A Streptococcal Diseases

• Pharyngitis (“strep throat”)-inflammation of the pharynx

• Scarlet fever-rash that begins on the chest and spreads across the body

• Pyoderma-confined, pus-producing lesion that usually occurs on the face, arms, or legs. Can become erysipelas if surrounding lymph nodes involved

• Streptococcal toxic shock syndrome-bacteremia and severe multisystem infections

Group A Streptococcal Diseases

• Necrotizing fasciitis-toxin production destroys tissues and eventually muscle and fat tissue

• Rheumatic fever-inflammation that leads to damage of heart valves muscle

• Glomerulonephritits-inflammation of the glomeruli and nephrons which obstruct blood flow through the kidneys

Diagnosis, Treatment, and Prevention

• Diagnosis

• Observation of Gram-positive bacteria in short chains or pairs or immunological tests that identify the presence of group A streptococcal antigens

• Streptococci are normally in the pharynx so their presence in a respiratory sample is of little diagnostic value

Diagnosis, Treatment, and Prevention

• Treatment

• Penicillin is very effective

• Prevention

• Antibodies against M protein provide long-term protection against future infection of S. pyogenes, but only if it is the same strain

Group B Streptococcus: Streptococcus agalactiae

• Gram-positive cocci that divide to form chains

• Distinguished from group A streptococcus by its buttery colonies and smaller zone of beta-hemolysis on blood agar plates and its resistance to bacitracin

• Normally colonizes the lower gastrointestinal, genital, and urinary tracts

Pathogenicity and Diseases

• Pathogenicity

• Often infects newborns who have not yet formed type-specific antibodies and whose mothers are uninfected (and so do not provide passive immunity)

• Produces various enzymes whose roles in causing disease is not yet understood

• Diseases

• Most often associated with neonatal bacteremia, meningitis, and pneumonia

• Immunocompromised older patients are at risk from group B streptococcal infections

Diagnosis, Treatment, and Prevention

• Diagnosis

• Agglutination and ELISA test utilizing antibodies directed against the bacteria’s distinctive cell wall polysaccharide

• Incubation of the bacteria with bacitracin which inhibits its growth

• Treatment

• Penicillin G, sometimes in combination with an aminoglycoside

Diagnosis, Treatment, and Prevention

• Prevention

• Prophylactic administration of penicillin at birth to children whose mothers’ urinary tracts are colonized with group B streptococci

• Immunization of women against group streptococci to prevent infection of future children

Alpha-Hemolytic Streptococci: The Viridans Group

• Lack group-specific carbohydrates and cannot be grouped by the Lancefield system

• Many produce a green pigment when grown on blood media

• Normally inhabit the mouth, pharynx, GI tract, genital tract, and urinary tract

• One of the causes of dental caries and dental plaques

• If enter the blood can cause meningitis and endocarditis

Streptococcus pneumoniae

• Gram-positive cocci that most commonly forms pairs but may also form chains

• Forms unpigmented, alpha-hemolytic colonies when grown on blood agar (anaerobic incubation produces beta-hemolytic colonies)

• Normally colonizes the mouths and pharynx but can cause disease if travels to the lungs

• Disease is highest in children and the elderly

Pathogenicity

• Phosphorylcholine-stimulates cells to phagocytize the bacteria

• Polysaccharide capsule-protects the bacteria from digestion after phagocytosis

• Protein adhesin-mediates binding of the cells to epithelial cells of the pharynx

• Secretory IgA protease-destroys IgA

• Pneumolysin-lyses epithelial cells and suppresses the digestion of the phagocytized bacteria

Diseases

• Pneumococcal pneumonia-bacteria multiply in the alveoli causing damage to the alveolar lining and an inflammatory response

• Sinusitis and otitis media-bacteria invade the sinuses or middle ear, often following a viral infection

• Bacteremia and endocarditis-bacteria in the bloodstream or in the lining of the heart

• Pneumococcal meningitis-bacteria that have spread to the meninges

Diagnosis, Treatment, and Prevention

• Diagnosis

• Gram strain of sputum smears

• Quellung reaction-anti-capsular antibodies cause the capsule to swell, confirming the presence of bacteria

• Treatment

• Penicillin

• Prevention

• Vaccine made from purified capsular material

• Provides long lasting immunity in normal adults but is not as effective in children, the elderly, or AIDS patients

Enterococcus

• Previously classified as group D streptococci but differed enough to be reclassified as a separate genus

• Form short chains and pairs and lack a capsule

• Found in the human colon but are rarely pathogenic at this site

• Can cause disease if they are introduced into other parts of the body, such as the urinary tract or bloodstream

Enterococcus

• Important cause of nosocomial infections

• Treatment is difficult because enterococci are often resistant to antimicrobials

• Prevention is difficult, especially in a health care setting, where patients’ often have weakened immune systems

Bacillus

• Gram-positive bacilli, that occurs singly, in pairs, or in chains

• Forms endospores

• Bacillus anthracis is a strict pathogen of animals and humans

• Primarily a disease of herbivores, but humans can contract the disease from infected animals

• Humans contract the bacteria via on of three routes

• Inhalation of spores

• Inoculation of spores into the body through a break in the skin

• Ingestion of spores

Pathogenicity and Diseases

• Pathogenicity

• Anthrax toxin

• Diseases

• Anthrax is the only disease caused by Bacillus anthracis

• Anthrax can have three clinical manifestations

• Gastrointestinal anthrax

• Rare in humans

• Intestinal hemorrhaging and eventually death

Pathogenicity and Diseases

• Cutaneous anthrax

• Produces a ulcer called an eschar and toxemia

• Inhalation anthrax

• Rare in humans

• Spores germinate in the lungs and secrete toxins that are absorbed into the bloodstream

• High mortality rate

Diagnosis, Treatment, and Prevention

• Diagnosis

• Presence of large, nonmotile, Gram-positive bacilli in clinical samples of the lungs or skin

• Treatment

• Ciproflaxacin and many other antimicrobials are effective against B.anthracis

• Prevention

• Control the disease in animals

• An anthrax vaccine is available but requires multiple doses and boosters

Clostridium

• Gram-positive, anaerobic, endospore-forming bacillus

• Ubiquitous in soil, water, and the gastrointestinal tracts of animals and humans

• The presence of endospores allows for survival in harsh conditions

Clostridium perfringens

• Commonly grows in the digestive tracts of animals and humans

• Produces 11 toxins that have various effects on the body and can result in irreversible damage

Clostridium perfringens

• Diseases

• Food poisoning

• Benign disease characterized by abdominal cramps and watery diarrhea

• Gas gangrene

• Endospores are introduced into the body through some traumatic event

• The endospores germinate and cause necrosis that is often accompanied by foul-smelling gaseous bacterial waste products

Diagnosis, Treatment, and Prevention

• Diagnosis

• The presence of more than 10⁵ bacteria in a gram of food or 10⁶ cells per gram of feces indicates the involvement of Clostridium in food poisoning

• Gas gangrene is usually diagnostic by itself

• Treatment

• Food poisoning is self-limited

• Gas gangrene is treated by removing the dead tissue and administering large doses of penicillin

Diagnosis, Treatment, and Prevention

• Prevention

• Difficult to prevent because it is so common

• Proper cleaning of wounds can often prevent gas gangrene

Clostridium difficile

• Common member of the intestinal microbiota

• Opportunistic pathogen in patients treated with broad-spectrum antimicrobial drugs

• Minor infections can result in a self-limiting explosive diarrhea

• Serious cases can cause pseudomonas colitis

• Can result in perforation of the colon, leading to massive internal infection by fecal bacteria and eventual death

Clostridium difficile

• Diagnosed by isolating the organism from feces or by demonstrating the presence of toxins via immunoassay

• Minor infections are usually resolved by discontinuing use of the antimicrobial drug in use

• Serious cases are treated with antibiotics

• Proper hygiene is critical for limiting nosocomial infections

Clostridium botulinum

• Anaerobic, endospore-forming, Gram-positive bacillus

• Common in soil and water

• Botulism results when the endopsores germinate and produce botulism toxin

• The different botulism toxins are the deadliest toxins known

Diseases

• Botulism is not an infection, but an intoxification caused by the botulism toxin

• 3 forms of botulism

• Food-borne botulism

• Usually occurs due to the consumption of toxin in home-canned foods or preserved fish

• Can result in a progressive paralysis that results in death due to the inability to inhale

Diseases

• Infant botulism

• Results from the ingestion of endospores, which germinate, and colonize the gastrointestinal tract due to the lack of sufficient numbers of normal microbiota

• Symptoms include constipation and “failure to thrive”, but paralysis and death are rare

• Wound botulism

• Wound becomes contaminated with endospores

• Symptoms are the same as with food-borne botulism

Diagnosis, Treatment, and Prevention

• Diagnosis

• Symptoms of botulism are diagnostic

• Confirm diagnosis by culturing the organism from food, feces, or the patient’s wound

• Treatment

• Can involve three approaches

• Repeated washing of the intestinal tract to remove Clostridium

• Administer antibodies against botulism toxin to neutralize toxin in the blood

• Administer antimicrobials drugs to kill clostridia in infant botulism cases

Diagnosis, Treatment, and Prevention

Prevention

• Proper canning of food to prevent contamination

• Infants should not consume honey under the age of 1

Clostridium tetani

• Endospore-forming, obligately anaerobic, Gram-positive cocci

• Ubiquitous in soil, dust, and the GI tract of animals and humans

• Tetanus results when the bacterial endopsores germinate and produce tetanus toxin

• Tetanus results in spasms and contractions that can result in death because patients can’t exhale

Diagnosis, Treatment, and Prevention

• Diagnosis

• Characteristic muscular contraction

• The bacteria is rarely isolated from clinical samples because it grows slowly and is sensitive to oxygen

• Treatment

• Thorough cleaning of wounds to remove endospores

• Passive immunization with immunoglobulin directed against the toxin

• Administration of antimicrobials

• Active immunization with tetanus toxoid

Diagnosis, Treatment, and Prevention

• Prevention

• Immunization with tetanus toxoid

Listeria

• Gram-positive non-spore-forming, coccobacillus

• Found in soil, water, mammals, birds, fish, and insects

• Enters body in contaminated food and drink

• Listeria produces no toxins or enzymes

• Virulence is directly related to the bacteria’s ability to live within cells

Diagnosis, Treatment, and Prevention

• Diagnosis

• Presence of the bacteria in the cerebrospinal fluid

• Rarely seen by Gram-staining because so few Listeria cells are required to produce disease

• Treatment

• Most antimicrobial drugs inhibit Listeria

• Prevention

• Difficult because the organism is ubiquitous

• At risk individuals should avoid undercooked vegetables, unpasteurized milk, undercooked meat, and all soft cheeses

Corynebacterium

• Ubiquitous on plants and in animals and humans

• Colonizes the skin and the respiratory, gastrointestinal, urinary, and genital tract

• Corynebacterium diphtheriae, the cause of diphtheria, is the most widely known

• Transmitted from person to person via respiratory droplets or skin contact

• Endemic in poor parts of the world that lack adequate immunization

• Diphtheria toxin is responsible for the signs and symptoms of diphtheria

Disease

• Diphtheria toxin inhibits polypeptide synthesis which results in cell death

• Infections are asymptomatic or produce mild respiratory disease in immune or partially immune individuals

Disease

• Severe respiratory infections of nonimmune patients produce the signs and symptoms of diphtheria

• Pseudomembrane results from fluid that has thickened and adheres throughout the respiratory tract

• The pseudomembrane can completely occlude the respiratory passages and cause suffocation

• Cutaneous diphtheria causes cell death and formation of a pseudomembrane on the skin

Diagnosis, Treatment, and Prevention

• Diagnosis

• Initial diagnosis is based on the presence of pseudomembrane

• Absolute identification is based on the Elek test

• Antibodies against the toxin react with toxin in a sample of fluid from the patient

• Treatment

• Administration of antitoxin to neutralize toxin before it binds to cells

• Penicillin and erythromycin kills the bacteria

Diagnosis, Treatment, and Prevention

• Prevention

• Immunization with the DPT vaccine

Mycobacterium

• Cell wall contains a waxy lipid called mycolic acid

• The unusual cell wall results in a number of unique characteristics

• Slow growth

• Protection from lysis once the bacteria are phagocytized

• Capacity for intracellular growth

• Resistance to Gram-staining, detergents, many antimicrobial drugs, and dessication

Mycobacterium

• 3 main mycobacterial diseases

• Tuberculosis

• Leprosy

• Opportunistic infections in AIDS patients

Tuberculosis (TB)

• Respiratory disease cause by Mycobacterium tuberculosis

• Cases are declining in the United States but it is pandemic in other parts of the world

• Virulent strains of M.tuberculosis contain the cell wall component, cord factor, that is necessary to cause disease

Tuberculosis (TB)

• 3 types of tuberculosis

• Primary TB

• Results from the initial infection with M.tuberculosis

• Secondary TB

• Reestablishment of an active infection after a period of dormancy

• Disseminated TB

• Results when the infection spreads throughout the body

Diagnosis, Treatment, and Prevention

• Diagnosis

• Tuberculin skin test identifies individuals with previous exposure to M. tuberculosis by the presence of a hard, red swelling at the test site

• Chest x-rays are used to identify individuals with active disease

• Treatment

• Treatment with common antimicrobials is difficult because the bacteria grow slowly and can live within macrophages

• Combination therapy must be used for a number of months to treat the disease

Diagnosis, Treatment, and Prevention

• Prevention

• Prophylactic use of antibacterial drugs is used to treat patients who have shown a conversion from a negative to a positive skin test or were exposed to active cases of tuberculosis

• Inmmunization with BCG vaccine is used in countries where TB is common

Leprosy

• Caused by Mycobacterium leprae

• Bacteria have never been grown in cell-free culture

• Cases of leprosy are becoming relatively rare

• Transmission is via person-to-person contact or through a break in the skin

Diagnosis, Treatment, and Prevention

• Prevention

• Primarily prevented by limiting exposure to the pathogen

• BCG vaccine provides some protection

Mycobacterial Infections in AIDS Patients

• Mycobacterium avium-intracellulare is the most common mycobacterial infection among AIDS patients in the United States

• Infections are a result of ingestion of contaminated food or water

• Infections can simultaneously affect almost every organ and result in massive organ failure

• Treatment is difficult due to the disseminated nature of the infection

Propionibacterium

• Small, Gram-positive rods that are often found on the skin

• Propionibacterium acnes is the species most commonly involved in human infections

• Causes much of the acne of adolescents and young adults

• May also be an opportunistic pathogen

• Treatment often involves the use of antimicrobial drugs though many cases require no treatment

Nocardia asteroides

• Common inhabitant of soils rich in organic matter

• Produces opportunistic infections in numerous sites

• Pulmonary infections

• Develop from inhalation of the bacteria

• Produce pneumonia

• Cutaneous infections

• Result form introduction of the bacteria into wounds

• Produce mycetoma, a painless, long-lasting infection characterized by swelling, pus production, and draining sores

Nocardia asteroides

• Central Nervous system infections

• Result from the spread of the bacteria in the blood

• Prevention of nocardial disease involves avoiding exposure to the bacterium in soil

Actinomyces

• Normal member of the surface microbiota of human mucous membranes

• Produces opportunistic infections of the respiratory, gastrointestinal, urinary, and female genital tracts

• Actinomycosis results when the bacteria enters breaks in the mucous membrane

• Disease is characterized by the formation of many abscesses connected by channels in the skin or mucous membranes

• Diagnosis of actinomycosis can be difficult because other organisms cause similar diseases

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