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Chap 30 Person to person bacterial diseases Lecture #24- Strep and Staph Non-sporulating Gram+ bacteria Staphylococcus, Streptococcus, Lactobacillus, Leuconostoc Lecture Overview This lecture will look at two bacteria that are generalist pathogens that can manifest a number of different diseases....
Chap 30 Person to person bacterial diseases Lecture #24- Strep and Staph Non-sporulating Gram+ bacteria Staphylococcus, Streptococcus, Lactobacillus, Leuconostoc Lecture Overview This lecture will look at two bacteria that are generalist pathogens that can manifest a number of different diseases. They belong to the genera Streptococcus and Staphylococcus. Lecture Objectives After this lecture you should be able to identify the battery of virulence factors utilized by Streptococcus and Staphylococcus. You should be able to describe a superantigen and the role of biofilms and antiobiotic resistance in pathogenesis. Microorganisms and Concepts Staphylococcus sp. • “flesh-eating” bacteria • virulence factors • exotoxins • superantigen • protein A Streptococcus sp. Streptococcus The Flesh-eating Bacteria "Killer bugs are in my face" screamed a headline as Britain's tabloids created panic with graphic descriptions of the effects of a strain of Streptococcus pyogenes (Group A streptococcus), a bacteria that, in severe cases, can destroy tissue as fast as surgeons can cut it out. An unexplained proliferation of seven cases around the city of Gloucester had the British press predicting an epidemic, and British public health officials had to fight to bring the panic under control. This bacteria, medically known as Streptococcus pyogenes or Group A streptococcus, has been made famous in recent times by media reports of a flesh-eating bacteria which claims the lives of up to 25% of its victims. In 1990, it was also responsible for the death of the famous puppeteer and creator of the Muppets, Jim Henson. IN THE LATE AFTERNOON OF THURSDAY, DECEMBER 1, 1994, a media release was issued by the Bloc Quebecois from Ottawa stating that Lucien Bouchard had undergone surgery to remove his left leg due to a serious infection popularly known as "the flesh-eating disease." Streptococcus • The genus Streptococcus, a heterogeneous group of Gram-positive bacteria, has broad significance in medicine and industry. • Various streptococci are important ecologically as part of the normal microbial flora of animals and humans; some can also cause diseases that range from subacute to acute or even chronic. • Among the significant human diseases attributable to streptococci are scarlet fever, rheumatic heart disease, glomerulonephritis, and pneumococcal pneumonia. Streptococci are essential in industrial and dairy processes and as indicators of pollution. • The bacteria was identified as early as 1884 from patients with skin infections. It is identifiable as a spherical cell 0.6-1.0 um in diameter and occurs as pairs or as short chains in clinical specimens. • It is usually grown in the laboratory with the supplementation of blood or human serum. •Streptococcus pyogenes is responsible for a number of different diseases including: 1. Streptococcal pharyngitis (Streptococcal sore throat). 2. Scarlet fever. 3. Skin infections. 4. Necrotising fasciitis or Streptococcal gangrene, the flesh-eating disease. 5. Streptococcal toxic shock syndrome (STSS). 10 1. Streptococcal pharyngitis (Strep throat) • This disease occurs primarily among children 5-15 years of age, with the peak incidence occurring during the first few years of school. • The disease is spread from person to person via droplets of saliva or nasal secretions. •The symptoms include sore throat and sometimes may be associated with malaise, feverishness and headache. Diagnosis is made clinically and on isolation of the bacteria from a throat swab. 12 2. Scarlet fever • This disease results from the release of toxic substances by Streptococcus pyogenes. • If it occurs, it is usually associated with Streptococcal throat infections. • associated with a rash which appears as a diffuse red blush with many points of deeper red. • Treatment is penicillin. 3. Streptococcal pyoderma • begins as a flat sore on the skin which then becomes fluid filled and develops pus and crusting. • impetigo 4. Necrotising Fasciitis or Streptococcal Gangrene (The Flesh-eating Bacterial Disease) • rare infection of the skin and deeper tissues characterised by extensive and rapidly spreading death of tissue and underlying structures. • described in China as early as 1924. • it begins at a site of trivial or even inapparent trauma. It begins as an area of mild redness on the skin, but over the next 2-3 days undergoes a marked change. The inflammation becomes more pronounced, the skin becomes dusky and then purplish, and then bloody blisters develop in the skin. Unless appropriate medical treatment is undertaken the process may quickly march over large areas of the body. The patient is very ill and death rates are high even with appropriate medical treatment. • Treatment includes appropriate surgery and removal of all dead tissue and antibiotic therapy. Necrotizing fasciitis is an infection of the soft tissue that causes necrosis subcutaneous tissue. It most commonly affects areas of the groin, abdomen, or extremities. It is one of the fastest spreading infections known, and without treatment can lead to death. 17 5. Streptococcal Toxic Shock Syndrome (STSS) • illness is similar to necrotising fasciitis however the patient will also develop shock and failure of multiple organs including: kidneys; heart; lungs; liver and brain. • Treatment involves intensive care, surgical care and antibiotic therapy. Pathogenesis Streptococci are members of the normal flora. Virulence factors of group A streptococci include: (1) M protein and lipoteichoic acid for attachment; (2) a hyaluronic acid capsule that inhibits phagocytosis; (3) other extracellular products, such as pyrogenic (erythrogenic) toxin, which causes the rash of scarlet fever; and (4) streptokinase, streptodornase (DNase B), and streptolysins. • Nongroup A strains have no defined virulence factors. Streptococcus pyogenes infects the host by the following sequence of events. 1.The bacteria produces pyrogenic exotoxins A and or B, which can be found in severe infections. The exotoxins are toxins that are released extracellularly as the organism grows. 2.The exotoxins and the surface M-proteins act as superantigens. Superantigens cause the host damage by massive stimulation of the immune system. 3.The antigen binds to the Beta-chain of the T-cell receptor in a location that is not the normal binding site. 4. Leads to overproduction of T-cells in the area of bacterial growth Pathogenic sequence of events (cont’d). 5.The T-cells secrete large amounts of effector cells causing inflammation, tissue destruction, and death in approximately 30% of cases. This tissue destruction is what gives this strain of Streptococcus the name "flesh-eating bacteria". The bacteria spread so quickly because they secretes streptokinase, a fibrinolytic substance that dissolves clots that would have otherwise prevented further growth and invasion. Normal interaction of a macrophage or other APC and a Thelper cell (left) compared with the interaction of an APC and a T cell mediated by superantigens (right). Th cell TCR Antigen MHC II Antigen-presenting cell Superantigen Superantigens • bacterial and viral proteins • stimulate stronger immune response than normal antigens by “tricking” T cells into activation although they have not been triggered by a specific antigen • stimulate T cells to proliferate nonspecifically • Host–mediated pathogenesis 24 Superantigens… • stimulate release of massive quantities of cytokines from T cells – may result in circulatory shock and multiorgan failure • examples – staphylococcal enterotoxin B • causes food poisoning • is on the Select Agent List as a potential agent of terrorism – the toxin that causes toxic shock syndrome – mouse tumor virus superantigen – putative proteins from rabies viruses 25 Photograph of Streptococcus pyogenes killing white blood cell Morphology of the streptococci in comparison with staphylococci. Streptococci divide in a single plane and tend not to separate, causing chain formation. Group A Streptococcus Staphyloccoci Staphylococci can cause many forms of infection. (1) S. aureus causes superficial skin lesions (boils, styes. impetigo) and localized abscesses in other sites. (2) S.aureus causes deep-seated infections, such as osteomyelitis and endocarditis and more serious skin infections (furunculosis). (3) S. aureus is a major cause of hospital acquired (nosocomial) infection of surgical wounds and, with S. epidermidis, causes infections associated with indwelling medical devices. (4) S. aureus causes food poisoning by releasing enterotoxins into food. (5) S. aureus causes toxic shock syndrome by release of superantigens into the blood stream. (6) S. saprophiticus causes urinary tract infections, especially in girls. (7) Other species of staphylococci (S. lugdunensis, S. haemolyticus, S. warneri, S. schleiferi, S. intermedius) are infrequent pathogens. Staphylococcal Diseases • harbored by asymptomatic carriers or active carriers (have the disease) – spread by hands, inanimate objects or expelled by respiratory tract, or through blood • may produce disease in almost every organ and tissue • immune compromised most at risk 32 33 Staphylococcal Scalded Skin Syndrome (SSSS) • caused by strains of S. aureus that carry a plasmid-borne gene for exfoliative toxin (exfoliatin) • epidermis peels off revealing red area underneath • diagnosis – isolation/identification of staphylococcus involved or use of commercial kits 34 Scalded skin syndrome Superficial folliculitis Carbuncle Deep folliculitis 35 Impetigo Furuncle Impetigo caused by S. aureus or S. pyrogenes Impetigo commonly affects the face, arms, buttocks or waste, with initial redness which can develop into weeping spots and then crusts. Pathogenesis • S. aureus expresses many potential virulence factors. (1) surface proteins that promote colonization of host tissues (2) invasins that promote bacterial spread in tissues (leukocidin, kinases, hyaluronidase) (3) surface factors that inhibit phagocytic engulfment (capsule, Protein A); (4) biochemical properties that enhance their survival in phagocytes (carotenoids, catalase production); (5) immunological disguises (Protein A, coagulase, clotting factor) (6) membrane-damaging toxins that lyse eukaryotic cell membranes (hemolysins, leukotoxin, leukocidin (7) exotoxins that damage host tissues or otherwise provoke symptoms of disease (8) inherent and acquired resistance to antimicrobial agents • Coagulase-negative staphylococci are normally less virulent and express fewer virulence factors. Virulence determinants of Staphylococcus aureus • bacteria on that catheter creates a biofilm • once in the bloodstream, the bacteria can quickly infect other parts of the body Slime Producers (SP) • produced by pathogenic strains of Staphlococccus that is a viscous extracellular glycoconjugate that allows bacteria to adhere to smooth surfaces and form biofilms such as on medical devises and implants • inhibits neutrophil chemotaxis, phagocytosis, and antimicrobial agents 40 Slime and biolfilms. (Left) Cells of S. aureus, one of which produces a slime layer (capsule). (Right) A biofilm on the inner surface of an intravenous cathater. Extracellular polymeric substances, most polysaccharides, surround and encase the bacteria. 41 Figure 38.23 Methicillin resistant S. aureus wound. 42 Methicillin-resistant Staphylococcus aureus - MRSA - foun d in Canadian Pigs and Farmers - Do MRSA Illnesses have a food connection? Posted on November 10, 2007 A study published in Veterinary Microbiology found methicillinresistant Staphylococcus aureus (MRSA) is widely common in Canadian pig farms and pig farmers, signaling to some that animal agriculture as a source of the deadly bacteria. The Veterinary Microbiology study (Khanna et al. Veterinary Medicine 2007) is the 1st to show that North American pig farms and farmers commonly carry MRSA. Researchers looked for MRSA in 285 pigs in 20 Ontario farms and found MRSA at 45 percent of farms (9/20) and in nearly one in 4 pigs (71/285). One in 5 pig farmers studied (5/25) also were found to carry MRSA, a much higher rate than in the general North American population. The strains of MRSA bacteria found in Ontario pigs and pig farmers included a strain common to human MRSA Nov 22, 2022