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1、細菌學名,疾病？症狀？,如何造成疾病？（致病機制）,治療？,預防？,診斷？,型態生長特性生化反應血清學反應,細菌本身：侵襲性（毒力因素？）；產毒力（毒素？）宿主因素：抵抗力？易感因素？如何感染：途徑？媒介？,抗生素？（抗藥性？）；抗毒素？；症狀治療？,環境及個人衛生？疫苗？,A菌,B菌,Name(Binomial nomenclature)?,Diseases?Symptoms?,Pathogenesis mechanism?,Treatment?,Prevention?,Diagnosis?,MorphologyGrowth propertiesBiochemical reactionsSe
2、rological tests,Bacterial virulence factors:invasiveness?toxins?Host factors:defense mechanism?predisposing factors?Route of infection?Vectors?,Antibiotics(drug resistance?);Antitoxins?Supportive therapy?,Sanitation?Vaccination?,Bacterium A,Bacterium B,Pyogenic Cocci,Staphylococcus gram-positive,Str
3、eptococcus gram-positive,Neisseria gram-negative,Stapylococcus and related organisms,S.aureus:major pathogen for humans,may cause suppuration,abscess formation,scalded skin syndrome,toxic shock syndrome and food poisoning.S.epidermidis:may cause infection from prosthetic devices.S.saprophyticus:may
4、cause urinary tract infections(UTI)in young women.S.capitis:endocarditis,UTI,and opportunistic infections.S.haemolyticus:endocarditis,UTI,and opportunistic infections.Micrococcus spp.:opportunistic infections.Stomatococcus mucilaginosa:endocarditis,opportunistic infections.Alloiococcus otitidis:chro
5、nic middle ear infection.,StaphylococciNonmotile,spores(-).Grow readily on most bacteriological media;facultative anaerobic.Grow most rapidly at 37 oC,but form carotenoid pigment best at room temperature under aerobic condition on solid medium.Produce catalase.Relatively resistant to drying,heat(40o
6、C)and 10%NaCl.,Gram-positive cocci(a bunch of grapes),Morphology and Identification,Structure of staphylococcal cell wall,CapsuleNot readily seen in vitroAt least 11 types in S.aureusInhibiting phagocytosis by polymorphonucleocytes,Slime layer Loose-bound,water-soluble filmFacilitates bacterial adhe
7、rence to tissues or foreign bodies and,consequently,biofilm formation(important for the pathogenesis of coagulase-negative staphylococci),PeptidoglycanHas endotoxin-like activityinduces production of cytokinesactivates complementinduces aggregation of polymorphonucleocytes,Teichoic acids and lipotei
8、choic acidsBind covalently to peptidoglycan;species-specific;bind to fibronectin of host cells(adherence);antibodies may be found in systemic staphylococcal disease,particularly endocarditis.,Protein A:present on the surface of S.aureus strains,but not other species.Binds to the Fc portion of IgG ex
9、cept IgG3,preventing clearance of bacteria.,Coagulase(clumping factor)Produced by most S.aureus on the cell wall surface;binds to fibrinogen and converts it to fibrin,resulting in aggregates of bacteria.,Other adhesins bind with collagen,elastin and fibronectin,Coagulase-positive vs.coagulase-negati
10、ve staphylococci,Cytotoxinsa-toxin:pore-forming,cytotoxic to many types of cells including muscle cells.b-toxin:degrades sphingomyelin and is toxic for many kinds of cells,including human RBCs.g-toxin:bicomponent toxins,pore-forming.d-toxin:has detergent-like activity.P-V leukocidin:similar to g-tox
11、in in structure,kills WBCs of many animals and release the lysosomal enzymes.Associated with severe pulmonary and cutaneous infections.,Pathogenesis and ImmunityS.aureus can produce diseases both through invasiveness and production of toxins.,Toxins,Exfoliative(epidermolytic)toxins:proteases that sp
12、lit desmoglein 1 of the intercellular bridges in epidermis;produced by about 5-10%of S.aureus;causes the generalized desquamation of the staphylococcal scalded skin syndrome(SSSS).Toxic shock syndrome toxin-1(TSST-1):superantigen,associates with fever,shock,desquamative skin rash of toxic shock synd
13、rome in humans.Enterotoxins:superantigens,at least 10(A,B,C1,C2,C3,D,E,G,H,and I)soluble toxins produced by about 50%of S.aureus.Heat-stable(100oC,30 min.)and resistant to the gastric acid and gut enzymes.Enterotoxins are produced in carbohydrate and protein foods.Causing emesis,a characteristic of
14、staphylococcal food poisoning.,Toxins(continued),Enzymes,Coagulase:bound and free forms.May deposit fibrin on the surface of staphylococci and alter their ingestion by and destruction within the phagocytic cells(associated with invasiveness).Fibrinolysin(staphylokinase):to dissolve fibrin clot.Catal
15、ase:to remove H2O2.Hyaluronidase:to facilitate spread of S.aureus in tissue.Lipase:associated with superficial skin infection.Nuclease:produced only by S.aureus.Penicillinase,Staphylococci can permanently(coagulase-negative strains)or transiently(S.aureus)colonize various areas of the human body,wit
16、h the anterior nasopharynx as the most common colonization site for S.aureus in older children and adults(30%of healthy adults)Nasopharyngeal or skin carriers of S.aureus are responsible for many hospital infections.S.aureus can be transmitted through direct personal contact or contact with contamin
17、ated fomites.Areas at highest risk for severe infections:new born nursery,ICU,operating rooms and cancer chemotherapy wards.,Epidemiology,Clinical Diseases,Cutaneous infections(folliculitis,e.g.,stye and acne;furuncles;carbuncles;impetigo):usually an intense,localized painful inflammatory reaction t
18、hat undergoes central suppuration and heals quickly when the pus is drained.Carbuncle patients frequently have systemic signs.,S.aureus,Wound infections:can occur after surgery or trauma,may involve skin,bone(osteomyelitis from an open fracture)or meninges(meningitis from skull fracture.),Bacteremia
19、Mostly results from surgery or continued use of intravascular catheters.Bacteria may spread to other body sites and cause endocarditis,hematogenous osteomyelitis and septic arthritis,meningitis,and pulmonary infection(hematogenous pneumonia,and empyema.),Clinical Diseases,Septic embolism,S.aureus(co
20、ntinued),Aspiration pneumonia caused by S.aureus is seen in very young,very old,cystic fibrosis patients,influenza,etc.,Staphylococcal scalded skin syndrome(SSSS or Ritter disease):forming large bullae or cutaneous blisters with clear fluid that contains no bacteria or leukocytes.Spreads rapidly.Occ
21、urs much more often to neonates and young children.,Clinical Diseases,S.aureus(continued),Bullous impetigo is a localized form of SSSS.Unlike the disseminated SSSS,the blisters contain the bacteria.Highly communicable,Food poisoning:caused by ingestion of preformed enterotoxin in food(meat and carbo
22、hydrates).Short incubation(1-8 hr).Violent nausea,vomiting and watery diarrhea;no fever;rapid convalescence.Staphylococcal enterocolitis occurs in patients who have received broad spectrum antibiotics(antibiotic-associated diarrhea).,Clinical Diseases,Toxic shock syndrome:abrupt onset of high fever,
23、vomiting,diarrhea,myalgia,scarlatini form rash,desquamation of palms and soles,and hypotension with cardiac and renal failure.This disease has occurred in children injected with contaminated vaccine(1928),and young women who used tampons(1980).This may also occur in children or in men with staphyloc
24、occal wound infections(half cases are caused by enterotoxin B and,rarely,enterotoxin C.),Clinical Diseases,S.epidermidis and other coagulase-negative staphylococci,Endocarditis:caused by infection of native(rarely)or prosthetic heart valves.Catheter and shunt infections:a major medical problem,becau
25、se catheters and shunts are commonly used in critically ill patients.Slime production that causes biofilm formation prevents the bacteria from antibiotics and inflammatory cells.Persistent bacteremia is generally observed.Prosthetic joint infections:localized pain and failure of the artificial joint
26、.Systemic signs are not prominent.Reinfection of new joint is increased in such patients.Urinary tract infections:UTI infection by S.saprophyticus occurs mostly to young,sexually active women.,Laboratory Diagnosis,Specimen:pus,sputum,blood,anterior nasal and perineal swabs,left-over food etc.Smear:e
27、xcept for abscess material,gram stain of the smear is usually not informative.Serology:antibodies against teichoic acid can be detected in patients with staphylococcal endocarditis,but not those with osteomyelitis or wound infection.Elevated antibody titers is an indication for prolonged antibiotic
28、treatment.,Laboratory Diagnosis,Culture:blood agar plates.Use 7.5%NaCl to inhibit contaminants.Mannitol-salt agar can be used as a selective medium for S.aureus.Hemolysis and pigment production may not occur until several days later and are optimal at room temperature.Identification:catalase test;co
29、agulase test.Fluorescent in situ hybridization(FISH)with a S.aureus-specific DNA probe can be used for identification of this organism in clinical specimens.Various subtyping methods(such as pulsed-field gel electrophoresis)are used for epidemiological purpose.,Drug resistance of S.aureusTetracyclin
30、e are used for long term treatment of acne or furunculosis.Abscess and other closed suppuration lesions are treated by drainage and antibiotics.Bacteremia,endocarditis,pneumonia and other severe staphylococcal infections:prolonged i.v.therapy with b-lactamase-resistant penicillins(e.g.methicillin,ox
31、acillin,etc.)Vancomycin is the most effective drug against staphylococci,but its use is restricted in most hospitals.,Treatment,Drug resistance of S.aureus1)Resistance to penicillin G,ampicillin,and similar drugs is common.2)Resistance to nafcillin,methicillin and oxacillin MRSA(ORSA):methicillin(ox
32、acillin)-multiresistant S.aureus,resulting from acquisition of mecA,which encodes a novel PBP(PBP2)that is not bound by b-lactams.MRSA strains are usually also resistant to tetracyclines,erythromycins and aminoglycosides.Remain susceptible to vancomycin.However,many strains have become moderately re
33、sistant to vancomycin(called vancomycin-intermediate SA,VISA)and,notably,two vancomycin-resistant strains(VRSA),have been isolated in USA since 2002.,Staphyloxanthin,the carotenoid pigment,acts as an anti-oxidant and helps the bacteria resist killing by the reactive oxygen species(ROS),such as O2,H2
34、O2 and HOCl,in neutrophils.Bacteria that lack this pigment grow normally,but are deficient in skin abscess formation.,New chemotherapy target:staphyloxanthin,Liu GY et al.,J.Exp.Med.202,209(2005),Early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis.A choles
35、terol biosynthesis inhibitor blocks staphyloxanthin biosynthesis,resulting in colorless bacteria with diminished virulence that were cleared by the innate immune system,Liu CI et al.,Science 319,1391(2008),Prevention and control,Chief sources of infection:shedding human lesions,contaminated fomites,
36、human respiratory tract and skin.Prevention of infection:cleansing of the wound and the application of an effective disinfectant.Prevention of wide dissemination from staphylococci carriers is very important(aerosols and UV of air have little effect).Rifampin plus a second antibiotics,or some topica
37、l agents,may suppress or cure of nasal carriage.Areas at highest risk for severe infections:new born nursery,ICU,operating rooms and cancer chemotherapy wards.While cases of infection by MRSA are mainly hospital-acquired,there are increasing numbers of community-acquired infections by newly emerging MRSA recently.,Pustular impetigo,Back,Carbuncle,Back,
