Respiratory Tract Pathogens Community Acquired (15)

Haemophilus influenzae Bordatella pertussis Legionella pneumophila Staphylococcus aureus Mycobacterium tuberculosis MOTT Streptococcus pneumoniae GAS- S. pyogenes

Chlamydia trachomatis C. pneumoniae C. psittaci Neisseria meningititis Histoplasma capsulatum Blastomyces dermatiditis Coccidioides immitis

Respiratory Tract Pathogens Nosocomial (6)

Legionella pneumophila Staphylococcus aureus Coagulase negative Staphylococci spp. Pseudomonas aeruginosa Enterococcus faecalis Candida spp.
Primarily affects infants and children

Meningitis (6)

Haemophilus influenzae Streptococcus agalactiae E. coli Streptococcus pneumoniae Listeria monocytogenes Neisseria meningitidis

May affect all ages

Sexually Transmitted Pathogens (4)

Diarrheal Pathogens Enteroinvasive (7)

Diarrheal Pathogens Enterotoxigenic (4) Diarrheal Pathogens Enteropathogenic (2)

Wound/Skin Pathogens (8)

Chlamydia trachomatis Neisseria gonorrhoeae Treponema pallidum Haemohpilus ducreyi Salmonellaspp. Shigella spp. Yersinia enterocolitica Campylobacter jejuni Francisella tularensis Listeria monocytogenes Enteroinvasive E. coli Shigella spp. Vibrio cholerae Enterotoxigenic E. coli Clostridium dificile Helicobacter pylori Enteropathogenic E. coli Staphylococcus aureus Pseudomonas aeruginosa Streptococcus pyogenes (GAS) S. agalactiae (GBS) Clostridium perfringens C. tetani Bacteroides fragilis Candida spp.

Urinary Tract Infections (6)

Outpatient E. coli Staphylococcus saprophyticus Enterococcus spp. Inpatient E. coli Enterococcus spp.

Zoonotic Diseases (10)

Glucose non-fermenters Salmonella spp. Campylobacter jejuni Francisella tularensis Listeria monocytogenes E. coli O157H7 Yersinia pestis Brucella spp. Chlamydia psittaci Borrelia burgdorferi Rickettsia ricketsii Respiratory tract (community acquired), Meningitis Disease: ranges from life threatening meningitis to otitis

Haemophilus influenzae Basic Characteristics

media
Gram negative rod Fastidious: needs factor X (hemin) and V (NAD/NADP) Normal URT flora Cause of meningococcemia and meningitis Polysaccharide capsule: six types a-f; type b is polyribosephospate (PRP);most invasive nonencapsulated strains are assoc. with otitis media,

bronchitis, sinusitis

Haemophilus influenzaeb Virulence/Pathogenicity

Process of infection:

Haemophilus influenzae Vaccine

Bordetella pertussis Basic Characteristics

Adhere to non-ciliated epithelial cells encapulated strains can invade subepithelium and get into bloodstream Can cross blood-brain barrier and get into CSF Endotoxin is responsible for fever and other manifestations of acute meningitis Bacteremia = complication Ab to the Type b capsule enhances phagocytosis PRP is not immunogenic in very young kids (10-20 mos) Solution (1988): complex PRP with protein antigens Highly effective, H. influenzae meningitis declined by more than 95% Respiratory Tract (Community acquired) Gram negative rod, aerobic Not part of URT flora Cause of whooping cough
Catarrhal phase (2 weeks): organism enters by inhalation, attaches to ciliated cells in nasopharynx. Spread causing paralysis of cilia and inflammatory response. Cough, runny nose, fever; most infectious stage Paroxysmal stage (2 weeks): bacteria proliferate, inflammatory response, impair mucociliary elevator, violent coughing episodes, lymphocytosis. Difficult to culture b/c induces paroxysms Convalescent stage (4-8 weeks): decrease in frequency and severity of coughing Complications: pneumonia, seizures, encephalopathy, death Virulence factors: Adhesins Tracheal cytotoxin (TCT) kills ciliated epithelia Adenylate cyclase mimics PT action on neutrophils Haemolysin kills respiratory epithelia Endotoxin - fever

Stages and complications of pertussis

Bordetella pertussis Virulence

Pertussis toxin: an AB toxin (A is active w/4 Binding); ADP ribosylating toxin makes G-protein

constitutively active so cAMP which inhibits neutrophil f(x)

Bordetella pertussis Vaccines

Old vaccine was whole cell vaccine with severe side

effects
New vaccine is acellular vaccine: pertussis toxin plus

other antigens (subunit vaccine)

Respiratory Tract (community acquired, noscomial) Gram negative rod Facultative intracellular parasite with fastidious growth requirements Present in soil and water; no person-to-person spread Requires special medium: buffered charcoal yeast extract Diseases: Nosocomial infections Legionnaires' disease - acute bronchopneumonia; can be fatal Pontiac Fever - acute febrile respiratory illness w/o pneumonia; self limiting Acquire by inhalation of aerosols of contaminated water Only minority of those exposed develop disease, risk

Legionella pneumophila Basic characteristics

Legionella pneumophila Legionnaires Disease

factors include smoking, old age, COPD, immunosupp

Begins with flu-like sx and develops into pneumonia Can have watery diarrhea, low blood O2 Multiplies in alveolar M Inhibits phagolysosome fusion Unusual lipid A LPS Engenders massive inflammatory response resulting in

Legionella pneumophila Virulence factors

most of the lung damage

Legionella pneumophila Immune defenses Legionella pneumophila Treatment

TNF- by M inhibit intracellular growth Once established, requires cell-mediated immune

response
Need antibiotics able to penetrate the cell - Erythromycin Prevention is to eliminate it from water sources such as

Staphylococcus aureus Basic Characteristics

Staphylococcus aureus Virulence Factors: Avoidance of Host Defense Staphylococcus aureus Virulence Factors: Host Damage

air conditioning Respiratory Tract (Commensal; Nosocomial); Meningitis Gram positive cocci in clusters coagulase +; catalase +; mannitol fermenter Normal flora of skin and nasopharynx Can survive for months in dried pus or sputum, no spores Diseases: wound infections, abscess, sepsis, food poisoning, scalded skin syndrome, enteritis Capsule anti-phagocytic Protein A anti-phagocytic; binds to Fc portion of IgG, inhibiting opsonization Coagulase causes clots to form which may physically limit access of M Catalase converts H2O2 to water to protect against ROS produced by phagocytes Peptidoglycan/teichoic acid activate complement Membrane Damaging Toxins - Leukocidin degranulate PMNs & M - Hemolysins (, pore forming toxin that damage phagocytes, platelets, RBCs, and other host cells Superantigen Toxins not directly toxic to cells

Staphylococcus aureus Toxinoses Staphylococcus aureus Treatment

Coagulase negative Staphylococcus

Mycobacterium tuberculosis Basic characteristics

Mycobacterium tuberculosis Outcome of infection

- Staphylococcal Enterotoxins encoded by lysogenic phage and cause food poisoning or if systemic TSS - Exotoxins are exfoliatin which causes scalded skin syndrome and TSS Toxin-1 Coagulase Diseases that are primarily due to excreted toxins Enterotoxins food poisoning; superantigens Exfoliatin scalded skin syndrome TSST-1 toxic shock syndrome; superantigen Incision and drainage, debridement, cleaning Penicillin resistance due to -lactamase production Methicillin resistant S. aureus (MRSA) Vancomycin resistant S. aureus (VRSA) S. epidermidis opportunistic nosocomial infections especially in a compromised host (TSS) or in the presence of a prosthetic device; produces surface exopolysaccharide (slime layer) that promotes adherence to foreign bodies S. saprophyticus female urinary tract infections Respiratory Tract (community acquired) Rod-shaped bacillus, thin and beaded Obligate aerobe, facultative intracellular pathogen Does not gram stain. Stained by acid fast method which makes use of fatty acids in cell well Unusual cell wall - high lipid content with mycolic acid, a fatty acid Very slow growth = 12-24 hr generation time, 3-4 weeks to culture on agar Types of infection: pulmonary, non-pulmonary, and disseminated In healthy individuals, Primary TB is usually selflimiting and goes undiagnosed (only 1% become disseminated) 10% of these will later have a secondary infection (5% in <2 yrs, 5% in >2 yrs) Persons with HIV who have had a primary infection have a 10% risk of developing a secondary infection every year
Person inhales 2-3 bacilli in a vapor droplet These are gobbled up by a M If M is activated, TB is killed (end of story) If M is not activated, TB multiplies and eventually kills M and is released (go on to next step) New Ms gobble up this TB and process repeats Infected M migrate to lymph nodes and lungs stimulating an immune response The cell mediated immune response occurs in 2-8 weeks and forms granulomas, containing infection, but does not kill all TB Eventually granulomas walled off by fibrin and called tubercles The bacilli in middle of tubercles can reactivate (10%) Center of granuloma liquefies, bacteria resume growth,

Mycobacterium tuberculosis Course of infection Primary Infection

Mycobacterium tuberculosis Course of Infection Secondary Infection Mycobacterium tuberculosis

and massive immune response initiated

Cavities form and bacteria is released into airway

resulting in classic symptoms of TB

The disease symptoms associated with TB are due to

Pathogenesis

host immune response The ability of TB to survive in M is critical to its survival and does this by Inhibiting phagosome-lysosome fusion Inhibiting phagosome acidification
Tuberculin Skin Test PPD (Purified Protein Derivative) DTH (Delayed Type Hypersensitivity) response is indicative of cellular immunity to TB (shows as reddening and thickening of skin) HIV pxs may not show PPD+ even if they have TB Cellular immunity to other mycobacteria may show PPD+ Sputum examination - more sensitive to get a specimen, stain acid fast stain, but takes a long time to grow on a plate (3-6 weeks) and can not tell the difference btw MTB and other mycobacteria 9-12 months with antibiotics (Rifampin, Isoniazid,

Mycobacterium tuberculosis Laboratory diagnosis

Streptomycin, and Ethambutol

Use DOTS (directly observed therapy short course) to

Mycobacterium tuberculosis Treatment

Mycobacterium leprae Basic characteristics

Mycobacterium Other Than Tuberculosis MOTT Basic Characteristics

Mycobacterium Other Than Tuberculosis MOTT Runyon Classification

Mycobacterium Other Than Tuberculosis MOTT

monitor patient compliance which reduces amount of time you have to take meds and reduces chance of antibiotic resistance occurring 85% cure rate for complete course; 40-60% mortality if untreated BCG is only current vaccine and its efficacy is somewhere between 0-80%. If vaccinated will show PPD+ Communicable disease but not highly infectious. Can have a 5 year incubation period so not much is known about initial infection Primarily affects skin, appendages and peripheral nerves Nonculturable in media or cell culture Two types: Tuberculoid good cell mediated response so most dmg is by host defense Lepramatous weak cell mediated response so get lots of bacilli in surface areas Taken up by M similar to MTB Large group of mycobacteria that are normal inhabitants of soil and water Some are opportunistic pathogens None are spread person-to-person All are acid-fast organisms (so acid-fast positive is NOT indicative only of TB) Infections will not produce positive PPD test Based on growth rates and colony pigmentation on agar Group I Photochromagens slow growers that produce yellow pigment when grown in light (M. kansasii, M. marinum) Group II Scotochromogens slow growers that produce pigment independent of light (M. scrofulaceum, M. ulcerans, M. gordonae) Group III Nonchromogens slow growers w/no pigment (M. avium complex(MAC)) Group IV rapid growers (M.fortuitum, M chelonei, M. abscessus) MAC (M. avium complex) found in water supplies; transmissible by inhalation or ingestion, but not

Pathogenic species of note

Mycoplasmas Basic characteristics

Mycoplasma pneumoniae Characteristics of Disease

Mycoplasma pneumoniae Virulence and Treatment

communicable; causes TB like pulmonary disease, especially in HIV pxs M. marinum, M. ulcerans, M. fortuitum, M. chelonei, and M. abscessus cause skin ulcers, may be introduced following a trauma Group of unusual bacteria that lack a rigid cell wall and have no cell wall murein Smallest of free-living organisms; not visible with normal microscopy Genome size is smaller than most bacteria and many metabolic pathways are absent accounting for slow growth even when necessary nutrients provided Causes atypical pneumonia or "walking pneumonia" to distinguish it from the lobar pneumonia caused by S. pneumoniae (other pathogens that cause atypical pneumonia are Chlamydia pneumoniae and Legionella pneumophila) Usually has less abrupt onset and milder course than pneumococcal pneumonia (scanty sputum, not much on a chest x-ray) Virulence Attachment structure at tip of bacteria allows it to attach to ciliated respiratory epithelial cells Produces H2O2 which causes cilia to stop beating Treatment: Must be with antibiotics other than lactams because there are no peptidoglycans in the cell wall Infection usually resolves by itself in 3-4 weeks The following species are common inhabitants of the GU tract of sexually active people: M. genitalium urethritis and cervicitis M. hominis - PID Ureaplasma urealyticum - urethritis Nosocomial; wound/skin Gram negative rod, glucose negative, oxidase positive Produces distinctive blue-green pignment Ubiquitous in nature (sink taps, showers, baths, fresh flowers, fruits, vegetables) Often grow in biofilms, very difficult to treat Disease: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection. Mucoid morphotype affects CF pxs Adhesins, flagella, endotoxin, proteases, lipases Exotoxin A - inhibits protein synthesis Organism is similar to that found in VAP in that they grow initially as single celled, motile organisms (planktonic growth) In CF px form biofilm which protects from antibiotics and host immune system This mucoid mode of growth triggers a severe immune response (PMN proteases cause extensive lung dmg) Once infected, almost impossible to eradicate Alpha hemolytic - Streptococcus pneumoniae - Viridans streptococci (many spp in oral cavity, S. mutans causes cavities) Beta hemolytic

Mycoplasmas Infections of GU Tract

Pseudomonas aeruginosa Basic characteristics

Pseudomonas aeruginosa Virulence

Pseudomonas aeruginosa Effect on CF patients

Classification of Streptococci

Streptococcus pneumoniae Basic characteristics

Streptococcus pneumoniae Route of Infection

Streptococcus pneumoniae Virulence factors

Streptococcus pneumoniae Treatment

Viridans (Oral) Streptococci (S. mutans, S. oralis, S. sanguis) Basic Characteristics

GAS Streptococcus pyogenes Basic Characteristics

GAS Route of infection

- Group A Strep (GAS) S. pyogenes - Group B Strep (GBS) S. agalactiae Gamma hemolytic - Enterococcus faecalis Gram + diplococci -hemolytic, catalase negative P-disc sensitivity (optochin) normal flora Diseases: respiratory URT bacterial pneumonia bacteremia Meningitis Otitis media Spread by aerosols Colonize nasopharynx (can be asymptomatic) Often follows lowering of host defense (e.g. mucous elevator); classic secondary infection following a viral URT S. pneumoniae can be killed by M so avoids them Inflammatory response is what does most of the damage Bacteria may enter bloodstream and cross blood-brain barrier Capsule antiphagocytic Cell wall constituents (peptidoglycan, teichoic acid) elicit immune response Pneumolysin lung damage Penicillin Vaccine: polyvalent and covers about 23 of the 80 serotypes; for adult at risk individuals: Elderly > 50 years of age Immunocompromised Patients with systemic disease like sickle cell New polyvalent (7 serpotypes) vaccine conjugated to protein has proven effective in kids Disease: subacute bacterial endocarditis (sbe) Commensal inhabitants of oral cavity Route of Infection enters bloodstream, usually due to minor trauma adheres to area of heart defect cause platelet aggregation Treatment hard to treat, drug resistance, can be lethal. Pxs at risk (heart valve lesions) should be put on prophylaxis before dental operations Chains of cocci; Beta-hemolytic, Agglutination assay positive, bacitracin sensitive Range of symptoms: no illness, mild illness (strep throat and impetigo/cellulites), severe illness (necrotizing fascitis, Toxic Shock Syndrome, scarlet fever) Can cause Sequela: rheumatic fever and acute glomerulonephritis Inhalation or contact with the skin Causes different diseases, based on exposure: 1. Strep throat- will resolve on its own 2. Impetigo- infection of epidermis 3. Cellulitis- Skin infection spread to subcutaneous tissue

GAS Sequela

Sequela can develop: 1. Rheumatic fever- autoimmune rxn to

s.pyogenes; cross reacts with M protein of cardiac myosin; streptolysin O causes cell lysis; causes heart valve scarring, risk of endocarditis 2. Acute Glomerulonephritis- kidney disfunction caused by immune complex deposition in kidney; damages glomeruli
M-proteins- antiphagocytic (bind factor H, triggering degradation of C3b), many different types, fxn as adhesions Hyaluronic acid- found on bacterial surface and in joints C5a peptidase- prevents recruitment of phagocytes Peptidoglycan- induces inflammation Exotoxins- superantigens, SpeA and C are encoded on lysogenic phage, important in TSS, scarlet fever, necrotizing fascitis Streptolysin O- damages heart muscle Hydrolytic enzymes- damage heart muscle

GAS Pathogenesis/Virulence Factors

GAS Treatment

GBS Streptococcus agalactiae Basic Characteristics

Enterococcus faecalis Basic characteristics

Enterococcus faecalis Disease and treatment

Salmonella Basic characteristics

Treat with penicillin Sequela can be prevented if strep throat is treated with antibiotic Some symptoms remain after treatment because symptoms are caused by SPE toxins Different types (I, II, III) based on differences in capsular antigens Route of infection: URT, found in vagina (10-30% women are carriers) Diseases: Neonatal sepsis/meningitis (early and late onset respectively) and post-partum sepsis (mother) Virulence Factors: capsule, c5a peptidase Treatment: give penicillin to pregnant carriers during labor Gram + cocci in pairs or short cahins (also known as Group D Strep) -hemolysis (none) normal gut and GU flora can grow in bile and ferment esculin (bile esculin +) Optochin resistant (means of distinguishing it from S. pneumoniae) Disease: subacute bacterial endocarditis (sbe) and UTI Major Nosocomial infection: cause disease when introduced into tissue or bloodstream (often due to catheters) Treatment: synergistic bactericidal antimicrobials penicillin (to weaken cell wall and give other antibiotic access) and an aminoglycoside (e.g. streptomycin) Vancomycin Resistant Enterococcus (VRE) is becoming a problem) Invasive GI disease Gram negative rod, facultative intracellular pathogen facultative anaerobe lactose negative enteroinvasive Epidemiology: chicken, eggs, dairy, beef; large inoculum Disease: typhoid fever gastroenteritis septicemia

 Caused by Salmonella typhi or S. paratyphii Transmitted person to person, by contaminated food,

Salmonella spp. Typhoid fever

Salmonella spp. Gastroenteritis

Salmonella spp. Septicemia

Salmonella spp. Virulence Factors

Salmonella spp. Vaccines

Shigella Basic characteristics

Shigella Virulence Shigella Pathogenesis

flies. Drinking a cup of straight salmonella would take a lot of the organism to infect, but food protects it from host immune system Humans are the reservoir Pathogenicity: crosses intestinal epitheliumtaken up by Mblood filtered by reticuloendothelial system proliferatebloodfever, malaise, can infect liver and other organs4-6 weekssome people become carriers Most common type of salmonella infection Large inoculum of infected animal product or contaminated food Animals are reservoir Pathogenicity invade in same way as Typhoid but not as virulent and M can kill easier so tends to stay local Symptoms: mild-severe diarrhea, nausea, fever, vomiting Characterized by high fever and bacteremia More common in AIDS pxs Facultative intracellular pathogens live and grow in M (so can resist host immune system) Can live in many environments by turning on and off certain adaptive genes Smooth LPS is necessary for virulence and probably invasion Flagella (H antigens) the synthesis of flagella requires phase variation between two distinct surface antigens. This change from one antigen to another may help it evade immune response Two vaccines for S. typhi, though neither confers complete protection (can be overwhelmed by large inoculum) Oral (live attenuated) Injected (killed) No vaccine for non-S. typhi Invasive and Toxin-mediated GI disease Gram negative rod, lactose negative Most virulent = Shigella dysenteriae Least virulent, most common in US = Shigella sonnei Disease: mild diarrhea to dysentery (painful, bloody fever) Unique characteristics: low inoculum ( 10) direct person to person contact (so common in institutional settings not sensitive to gastric acid Invasive capacity is most important factor (see pathogenesis card) Shiga toxin cytotoxic, inhibits protein synthesis in eukaryotic by cleaving 28s rRNA in ribosomes which is associated with HUS (Hemolytic Uremic Syndrome blood in urine) Organism attaches to host epithelium in colon It is endocytosed in a host-donated membrane bound vesicle where it replicates

 In the cytoplasm it binds and polymerizes actin which

Shigella Vaccines

Yersinia enterocolitica Yersinia pseudotuberculosis Basic Characterisitics

Campylobacter jejuni Basic Characteristics

Campylobacter jejuni Characteristics of Disease Virulence

Listeria monocytogenes Basic Characteristics

Listeria monocytogenes Disease Characteristics Virulence Francisella tularensis Basic Characteristics

propels it through the cytoplasm to the lateral wall (rarely transcytoses through the basal wall into blood stream) Moves into the neighboring cell by invaginating through both membranes leaving it inside a dbl membrane vesicle Still gets out and replicates Ultimate result is that it kills the cells which stimulates a massive immune response Attenuated vaccines have been developed that are effective, but it has been difficult to isolate safe (nonreverting) strains. Invasive GI Yersinia spp. (as opposed to Y. pestisplague) Gram negative bacilli Found in humans and most wild and domesticated animals Disease: Acute watery diarrhea with mesenteric lymphadenitis (swollen mesenteric lymph nodes mimics appendicitis) Can occasionally get systemic invasion due to organisms invading deeper tissues granulomas in liver and spleen Invasive GI bug Gram negative curved rods Grows on enriched medium under micro-aerophilic conditions (NOT standard conditions used in many labs, so have to request specifically) Epidemiology: birds, dogs, farm animal to humans via contaminated H2O (50% chickens)& unpasteurized milk Disease: watery diarrhea to shigella-like dysentery Virulence: The organisms invade much like Salmonella and Shigella. Also produce cytotoxin of unknown role Correlation between Campylobacter and GuillanBarre syndrome, an autoimmune disease against a bodys myelin. The antigen on Campylobacter apparently resembles the antigen on myelin so if body develops antibodies against Campylobacter Invasive GI bug Gram positive coccobacilli, often confused on gram stain with Group B strep Grows at 4oC (i.e. can live in the fridge) Outbreak due to eating contaminated food (especially dairy and processed meat hot dogs) Pregnant women and fetuses most susceptible Endocytosed in a vacuole Engulfed by and survive in M Escape vacuole via lysteriolysin O which disrupts vacuole membrane but not M membrane Replicate in M then escape into cell Invade neighboring cells same as shigella Gram negative, aerobic, non-motile coccobacilli Requires cysteine for growth Infection can occur following skin contact, ingestion, inhalation of organism The MOST virulent organism known (5 bacteria are

Francisella tularensis Characteristics of Disease

Vibrio cholera Basic characteristics

sufficient for infection) Transmitted by contact, ingestion, inhalation of organism via the blood or tissue of an infected animal (e.g. rabbit) Skin contact begins with an ulcer, followed by swollen lymph nodes, then septicemia with fever that can last 6 weeks; 35% mortality if untreated Inhalation leads to pneumonia (highest mortality) The infection resembles Typhoid The organism invades epithelia and reticular endothelial system Diarrheal (toxin-mediated) Gram negative, comma-shaped rod Epidemiology: water-borne, fecal oral Disease: painless, watery diarrhea, massive loss of fluid leading to extreme dehydration, metabolic acidosis, and hypokalemia
Cholera toxin (A &B) B subunit facilitates binding to epithelia and doing so splits the disulfide bonds holding A1/A2 subunit together, allowing A1 into cytoplasm A adenylate cyclase in cell has catalytic and regulatory subunits. Catalytic converts ATP to cAMP but requires GTP to be bound to Reg subunit (GTP quickly becomes GDP under normal conditions). Cholera Toxin attaches ADP ribose to R subunit which stabilizes GTP cAMP levels pumps ions into gut and prevents their intracellular reuptakewater rushes into gut from all tissues to balance the intra- and extracellular [ion] B 5 binding subunits Killed cholera vaccine that is safe but expensive,

Vibrio cholera Virulence

Vibrio cholera Vaccine

Helicobacter pylori Basic Characteristics

Helicobacter pylori Characteristics of infection

requires multiple doses, and confers limited protection A live vaccine is in the works where recombinant DNA technology is used to construct strains with the toxin genes deleted Gastrointestinal Gram negative spiral ("helical") rod Microaerophilic Disease: peptic ulcer disease Treatment: antibiotics and Pepto-bismol Bacteria binds to the stomach epithelia in the mucous layer, releasing a urease The urease breaks down urea into CO2 and NH3 which raises the pH around the bacteria Bacteria flourishes in this environment, producing toxins which kill the epithelia, stimulating immune response PMNs wall off the bacteria and necrotic area creating an abscess which further protects the organism from stomach acidity

Escherichia coli Basic characteristics

Gastrointestinal (toxin mediated, invasive), Bacteremia, Meningitis, UTI Gram negative, lactose and sorbitol fermenting rod (except EHEC = sorbital negative) Critical virulence properties are encoded on plasmids, lysogenic phage, and/or pathogenicity islands All have different virulence factors but also all must be able to adhere to intestinal epithelium in some way Treatment: fluid and electrolyte replacement; antibiotics

can exacerbate HUS Less invasivemore invasive: ETECEPECEHECEIEC Disease: ranges from a cholera-like syndrome to a

milder "traveler's diarrhea" non-bloody and w/o pus

Enterotoxigenic E. coli (ETEC)

Virulence: toxins carried on plasmids are heat-stable

Enteroinvasive E. coli (EIEC)

Enteropathogenic E. coli (EPEC)

Enterohemorrhagic E. coli (EHEC) Strain 0157H7

Bacillus anthracis Basic Characteristics

Bacillus anthracis Virulence Factors

Bacillus anthracis Pathogenesis

Bacillus anthracis Vaccine and Treatment Yersinia pestis Basic Characteristics

toxin (ST) or a heat-labile toxin (LT), colonization factor antigens (CFA) code for a specific adhesion pilli Disease: Shigella-like infection, cramps, pus and blood in stool Virulence: organism can penetrate the intestinal epithelium, usually in large intestine Disease: Associated with outbreaks of infant diarrhea Destroy brush border of epithelia but do not overtly invade cell Virulence: bacteria attaches to host cell via pilus but also has intimate association whereby it injects a protein into host cytoplasm, the host then presents this on cell surface where bug binds to it via Intimin. This bond causes cytoskeletal rearrangement of host cell resulting ultimately in necrosis and immune response Disease: hemorrhagic colitis with bloody diarrhea and abdominal cramping Hemolytic uremic syndrome, HUS, clots in kidney destroys RBCs and cause acute kidney failure. Virulence: Shiga-like toxin, pili Sorbital negative Gram positive spore-forming rod, occurs in chains, aerobic, non-hemolytic 3 forms of Anthrax- cutaneous (most common, black scab), inhalational (flu-like symptoms leading to respiratory arrest) and GI (rare, causes bloody emesis, acute abdominal pain, and occasionally bloody diarrhea, high mortality) Anti-phagocytic capsule Protective antigen aids in transportation of the two toxins into mammalian cells Lethal Toxin Edema Factor Organism is inoculated into skin, inhaled or ingested Capsule allows it to survive phagosytosis PA binds to cell and allows binding of LT and EF These are transported in a M to the lymph node where they are released, causing a massive immune response Vaccine is 90% effective but requires multiple shots and annual booster used mainly in military Treatment is Penicillin G and Ciprofloxin Zoonotic Disease Characteristics: "clothes-pin like" Gram negative rod, lactose negative Vector: flea Reservoir: rodents

Yersinia pestis Virulence Factors

Brucella spp. Basic Characteristics

Brucella spp. Pathogenesis

3 forms of Plague - bubonic spread by fleas, lymphadenopathy; septicemic is interim stage; pneumonic spread by person-to-person aerosols pain similar to "acute appendicitis" YOPS (Yersinia Outer Membrane Proteins) proteins involved in evading immune response (e.g. Fraction 1); genes encoding YOPS thought to be carried on plasmids or pathogenicity islands Fraction 1 Plasma Protease degrades complement components, regulates YOPS levels so can be taken up by M, also help spread by dissolving clots Endotoxin Zoonotic Disease Gram negative bacillus or coccobacillus, fastidious (does not grow on Mac), facultative intracellular, Epidemiology: diary cattle(B abortus), sheep/goat (B. melitensis), hogs/deer (B. suis), dogs (B. canis); veternarians, farmers; goat/cow milk Disease: often confused with disseminated tuberculosis; granulomatous lesions in nodes, spleen, liver, bone marrow, chills, night sweats, pains, etc. Killed at temp of pasteurization Portal of entry contact with infected animal tissue through abrasions in skin, oropharynx, and conjunctivae; ingestion of contaminated milk Clinical manifestations - organism is phagocytosed but not killed - localized in RE system - causes granulomatous and necrotic lesions in tissues of immune system - lymphadenopathy, hepatosplenomegaly - acute, febrile illness with chills, sweats, headaches GI

UTI E. coli are a different subset that those found in

Escherichia coli (UTI) Basic Characteristics

Causes over 80% of UTI One determinant of susceptibility is presence of

receptors that allow bacteria to adhere

Adhesins: - P-fimbriae or pili enhance early establishment of E. coli in urinary tract and important in ascending infections of kidney. Bind to galactose receptors so the # of Gal receptors a woman has affects her susceptibility - Type 1 fimbriae facilitate colonization of intestine, vagina, and bladder. Recognize mannose receptors. Can undergo a phase shift from fim (+) (can colonize) to fim (-) (can not colonize) once established. The advantage to fim (-) is that the do not bind to mannose receptors on PMNs LPS stimulates immune response Second most common cause of UTI in sexually

Escherichia coli (UTI) Virulence Factors

Staphylococcus saprophyticus Basic Characteristics Chlamydia spp. Basic characteristics

active women Part of normal UG flora Can cause cystitis but not sure if causes pyelonephritis No fimbriae; poorly understood virulence factors Tiny, gram negative obligate intracellular bacteria Several species with many different strains - Chlamydia trachomatis ocular, genital, LGV

Chlamydia trachomatis
Ocular strains

strains - Chlamydia psittaci - Chlamydia pneumoniae Cause trachoma, the most common form of preventable blindness (primarily in developing world) Infect epithelial cells of eye causing inflammation of conjunctiva and vascularization and scarring of cornea Scarring causes eyelid to turn inward and eyelashes abrade cornea resulting in ulceration, secondary bacterial infections, and eventually blindness
Most common STD in the world Many carriers asymptomatic but can still cause extensive genital tract damage - Urethritis sequelae can include epididymitis, prostatitis, and procitis - Cervicitis sequelae can include endometritis, salpingitis, perihepatitis Transmission 60-70% of females who have sex with infected males will develop infection Infection may lead to miscarriage Infant born to Chlamydia infected mother may develop conjunctivitis or pneumonia

Chlamydia trachomatis
Genital Strains

Chlamydia trachomatis LGV Strains

Chlamydia psittaci Basic Characteristics

Chlamydia pneumonia Basic Characteristics Chlamydia spp. Developmental Cycle

Lymphogranuloma venereum (LGV) more invasive than the other two LGV cause initial urethritis or cervicitis then rapidly penetrate through genital mucosa, infecting monocytes and M causing systemic infection Presents with inguinal lymphadenopathy Patients feel generally unwell Mat involve anorectal Chronic inflammatory lesions can lead to lymphatic obstruction, formation of rectal strictures. Women may experience extensive destruction of external genitalia Causes a flu-like respiratory infection that can become systemic Primarily a disease in animals (e.g. birds) that shed the organism when they are stressed (e.g. overcrowding). Humans can become infected by breathing the aerosolized feces Thus veterinarians, poultry workers, and slaughterhouse workers are at greater risk A recently identified bug that is the most common species of Chlamydia found in humans Causes acute respiratory illness Has been associated with cardiovascular disease in that it may contribute to atherosclerosis
Two stages in development: Elementary body early, infectious but non-growing Reticulate body - metabolically active and growing EB attach to columnar epithelial cells on mucosal surface and are internalized via endocytosis EB prevent the endocytotic vesicle from merging with lysosomes EB converts to RB, uses ATP from the hosts mitochondria, and begin to divide The membrane of the vesicle expands and is termed an inclusion RBs convert back to EBs, are released, and infect new

cells

Chlamydia trachomatis Pathogenesis

Chlamydia spp. Laboratory Diagnosis and Treatment

Neisseria gonorrhea Charactersitics of Disease

Neisseria gonorrhea Virulence

Neisseria gonorrhea Antibiotic Resistance

Neisseria meningitidis Basic characteristics

Neisseria meningitidis Virulence

Why do many people become colonized with N. meningitidis (dorms, army), but only a few get sick? Neisseria meningitidis Treatment/Vaccine

Many aspects of Chlamydial pathogenesis are not known, but there are two factors that appear to play a prominent role: Prolonged or Recurrent Inflammatory Disease Immune-mediated pathlogy These tend to affect damage via the epithelia in which the initial Chlamydia inclusions occurred Diagnosis traditionally relied on culture and microscopic techniques. Have begun to use DNA amplification such as PCR Treatment susceptible only to antibiotics that can penetrate eukaryotic cells In symptomatic patients, often get purulent discharge with pain In small percentage of cases get bacteremia-arthritis syndrome or disseminated gonococcal infection Pili LPS No capsule unlike N. meningitides, so harder for bug to evade phagocytosis Antigenic variation allows bacteria to evade antibody response and express different adhesins for different cells Low-level penicillin resistance due to chromosomal mutations High-level penicillin resistance due to -lactamase production Tetracycline resistance comes from plasmid encoded tetM gene Gram negative diplococci Present in nasopharynx normal flora Glucose(+); maltose (+) Causes meningococcemia and meningitis Petechiae, purpura fulminans, stiff neck, headache, fever, vomiting, confusion Disseminated intravascular coagulation (DIC) essentially septic shock, most likely in pxs with complement deficienct Polysaccharide capsule: antiphagocytic, several serotypes: A & C responsible for most epidemics B for most endemics Pili (fimbriae): adherence to different host cells; fiberlike appendage; subject to antigenic variation LPS: tissue damage, petechiae, shock, death; antigenically variable No known exotoxins Amount of anti-capsule antibody correlates with susceptibility to infection Colonization with nonpathogenic Neisseria or other encapsulated bugs produces protective cross-reactive antibody Late complement deficiencies make people more susceptible Tx: Penicillin (any antibiotic that penetrates in CSF) Vaccine: Group A & C No vaccine for Group B because it looks exactly

Haemophilus ducreyi (Chancroid) Basic Characteristics

Haemophilus ducreyi Characteristics of Disease

Treponema pallidum (Syphilis)

like a naturally occurring antigen in humans (sialic acid) and so is not immunogenic Vaccine effective in adults, not in children Gram negative fastidious rod Microaerophilic, inhibited growth at 37, grows on chocolate agar, so difficult to culture Growth is inhibited at 37oC which probably contributes to the fact that this bug NEVER causes systemic infection (only cutaneous) Thought that people do NOT develop protective immunity (somehow the bug is evading host defense) Confirmation is difficult requiring highly technical and expensive PCR which is unfortunate as this is primarily a disease of developing countries Genital ulcers that are distinguished from Syphilis and herpes b/c the bleed easily when gentle pressure applied Many develop bubos that can rupture Transmission from infected to uninfected requires a pre-existing break in the skin The bleeding associated with disease may contribute to these pxs being 300x more likely to contract HIV Ulcers may resolve spontaneously but often pxs become chronically infected due to auto-infection Spirochete, does not grow on artificial medium Motile due to presence of periplasmic flagella Syphilis can be transmitted from mother to fetus
Incubation period: 3 weeks Primary stage: chancre (painless dermal lesion), treponemes present in chancre and can be visualized w/dark field microscopy, lymph node involvement (2-6 weeks), 3-5x more likely to contract HIV Secondary stage: generalized rash esp. palms and soles (few weeks), fever, wart-like lesions; lots of treponemes Latent stage: months to years, only detectable serologically Late or tertiary stage: only a third of untreated patients develop this, can affect any organ: cardiovascular, neurosyphilis, gummatous syphilis; few treponemes present

Treponema pallidum Stages of syphilis

Treponema pallidum Diagnosis/Treatment of Syphilis

Dark field microscopy Serologic Tests 1.Non-treponemal tests cheap screening test, but high percentage of false positive and negative 2.Treponemal tests-confirmatory test, more accurate Treatment - Penicillin

Anaerobic bacteria

Anaerobic CNS infections

Gram positive cocci: Peptostreptococcus Gram positive spore-forming rod: Clostridium sp. Gram positive non-spore forming rods Actinomyces (branching), often confused with Norcardia Lactobacillus Propionibacterium Gram negative rods Bacteriodes fragilis Fusobacterium Prevotella Porphyromonas Brain abscess - result from chronic sinusitis,

mastoiditis, otitis media, lung abscess (Prevotella, Porhyromonas, Peptostreptococcus) Device-related meningitis - CSF shunts usually caused by Propionibacterium, common contaminant of CSF cultures

Anaerobic head & neck infections

Anaerobic pulmonary infections

Anaerobic female genital infections

Anaerobic Intra-abdominal infections

Clostridium spp. Basic characteristics

Clostridium dificile Basic Characteristics

Clostridium dificile Characteristics of Disease

Deep fascial space infections - can compromise airway Ludwig's angina - cellulitis of submandibular and sublingual spaces Retropharyngeal space infection - bulging posterior pharyngeal wall Actinomycosis or "lumpy jaw" - assoc. with dental procedures, infections usu. at angle of jaw; "sulfur granules" drain from sinuses Treatment: long-term penicillin (months, IVoral) Lung abscess: follows aspiration usu. kids, alcoholics key sign "fetid breath" organisms come from oral cavity such as Bacteroides, Prevotella, Porphyromonas, Fusbacterium, Peptostreptococcus usu. mixed with S. viridans Abscess formation and foul-smelling discharge Prevotella, Porphyromonas, Peptostreptococcus ("3 P's in the pelvis") Peritonitis Follows trauma to or necrosis of intestinal tract leading to normal bacteria being released into peritoneum Bacteroides fragilis and E. coli commonly work together synergistically Also can recover Peptostreptococcus and Prevotella Anaerobic, gram positive rod, "boxcar-shaped" Spore-former can survive hostile environments Soil - natural habitat Most rapidly growing organism (every 12 minutes) Disease: nosocomial diarrhea pseudomembranous colitis Predisposing factor = antimicrobial therapy Pathogenesis: Toxin A - enterotoxin, more important Toxin B - cytotoxin Treatment: metronidazole p.o. Organism is obtained from hospital environment Gut flora is altered by antimicrobial therapy Alteration in gut flora reduces its capacity to inhibit the growth of C. difficile C. dificile grows and produces toxins in gut Toxin mediates diarrhea and more severe manifestations such as non-specific and pseudomembranous colitis
Disease: gas gangrene, food poisoning Normal bowel flora Predisposing factor = traumatic wound, post-surgery Virulence: histotoxic Lecinthinase

Clostridium perfringens Basic Characteristics

Collagenase Hyaluronidase Treatment: debridement (amputation), leave wound open to air, Pen G C. septicum can also cause gas gangrene but is different in that (1) not due to trauma, (2) gram stain shows spores, and (3) 70% of these people have a carcinoma of the colon

Clostridium perfringens Characteristics of Disease

Inoculation of tissue during trauma Tissue damage restricts blood flow and oxygenation of tissue Organism either germinates from spores introduced into wound or vegetative organisms begin to grow in tissue - Very rapid growing organism - Gas is a metabolic by-product - Produces proteolytic and other toxins that degrade tissue There is no pus b/c WBCs recruited by immune response are quickly degraded
Disease flaccid paralysis leading to respiratory arrest Three forms of disease: Infant botulism - most common, honey/dirt ingestion, constipation, poor feeding, consume organism Food-borne botulism - improperly canned vegetables, soups, fish (home-canned), consume toxins Wound botulism organism in wound (Inhalational a bioterrorism agent) Pathogenesis: neurotoxin (A+B, most potent known) blocks Ach releaseflaccid paralysis difficulty swallowing, talking, sucklingdeath by respiratory arrest Tx: respiratory support plus antitoxin (from CDC)

Clostridium botulinum Basic Charcteristics

Clostridium tetani

Disease: tetanus Predisposing factor: trauma, usually stepping on nail Virulence: neurotoxinblocks inhibitionspastic paralysislockjaw or "trismus"respiratory failure Treatment: antitoxin, vaccine, respiratory support, pen G or metronzidazole
Disease: Lyme disease most common vector-borne dz in US 1 stage: characteristic "erythema migrans" central clearing , expanding periphery, fever, chills, ache/fatigue 2/3stage: arthritis, nervous (Bell's palsy) and CV system affected Vector: tick, Ixodes scapularis (east) pacificus (west) Reservoir: rodents, not deer Season: summer Characteristics: spirochete, does not gram stain, can be cultured Diagnosis: serology, antibiotics (doxycycline)in 1 stage

Borrelia burgdorferi

STARI (Southern Tick Associated Rash Illness) Basic Characteristics

Rickettsia rickettsii Basic Characteristics

This is a lyme-like disease Many who have developed this have been bitten by the

lone star tick which is not a competent vector for B. burgdorferi, the agent that causes Lyme disease STARI cases do not test positive in standard Lyme diagnostic tests Not sure what the agent responsible for STARI is Rickettsia are obligate intracellular bacteria Transmitted by arthropod vectors (ticks)

Rickettsia rickettsii Characteristics of Disease

Rickettsia rickettsii Route of Infection

Rickettsia grow in salivary glands of tick. Female tick takes a blood meal (several days), organism is delivered along with tick saliva (~10-24 hours of feeding needed to transmit infectious dose) Chills, fever, headache, rash Rash goes from erythematous maculopapular petechial on extremities petechial on trunk Fulminat vaculitis Rickettsiae attach to vascular endothelial cells Induce endocytosis Once in cell, escape vacuole via phospholipase (if dont escape they will be killed by lysosome) Divide in cell cytoplasm, parasitize host ATP, and exocytose at ends of hosts filapodia
When Rickettsia parasitizes host ATP, that leaves very little ATP available to run proton pumps in cell. Water pours into cell to maintain osmotic equilibrium Vascular epithelial cells are damaged by: Increase in reactive oxygen species (ROS) which dmg cell and decrease in anti-oxidants which protect cell Normally endothelium is resistant to platelet adherence to promote smooth blood flow, but these damaged cells cause platelets to adhere resulting in (1) DIC and (2) fewer platelets in ciurculation and thus clotting time elsewhere This leads to multi-organ system failure and shock

Rickettsia rickettsii Result of Infection

Rickettsia rickettsii Laboratory Diagnosis

Since this is an obligate intracellular parasite, it can not be grown on a plate Serological testing testing for antibodies against Rickettsia. Limitation is that early in disease there may not be enough antibody to be detectable

Sporothorix schenkii Basic Characteristics Disease Characteristics

Dimorphic fungus Yeast phase (37oC) elongate cigar shaped yeast cells Mold phase (25 oC) thin septate hyphae with delicate conidiophores bearing pear shaped conidia in clusters Disease - Sporotrichosis Most commonly disease of subcutaneous tissue Enters through traumatized tissue (e.g. via thorns) Lesions begin as painless papules and spread along lymphatic channels Disseminated sporotrichosis is rare infection of immunocompromised people Dimorphic fungus Mold phase barrel shaped arthrospores Yeast phase large round spherules which contain

Coccidioides immitis Basic Characteristics Disease Characteristics

endospores
Epidemiology: found in soils of arid areas (important

Histoplasma capsulatum Basic Characteristics

in differential diagnosis) Disease Valley Fever Acquired via inhalation of arthrospores Causes flu-like illness Dimorphic fungus Mold phase microconidia and tuberculated macrconidia Yeast phase small, oval (lemon shaped) intracellular yeasts, usually in M of lungs and RES Epidemiology: found in soils enriched with bird feces (starling roosts) and bat feces (caves)
Disease Histoplasmosis

Histoplasma capsulatum

Disease Characteristics Laboratory Diagnosis

Blastomyces dermatitidis Basic Characteristics Disease Characteristics

Acquired via inhalation of microconida Causes flu-like/TB-like illness Lab Diagnosis Demonstration of lemon shaped yeasts in M Presence of tuberculated macroconida Urinary Antigen Test Dimorphic fungus Mold phase not listed in syllabus Yeast phase thick walled with broad based bud Epidemiology associated with rotting organic matter Disease Blastomycosis Acquired via inhalation of micoconida Results in progressive pulmonary disease with

Paracoccidioides brasilensis Basic Characteristics

Opportunistic fungal infections (5)

Candida albicans

Cryptococcus neoformans

Aspergillus fumigatus

Zygomycetes

Pneumocystis carinii

granulomas Dimorphic fungus Mold phase identical to Blastomyces Yeast phase multiple buds showing ship wheel appearance Epidemiology soil of sub-tropical regions of Central and South America Candida albicans Cryptococcus neoformans Aspergillus Zygomycetes Pneumocystis carinii Characteristics: no mold phase, budding yeast Most common cause of nosocomial bloodstream infections at UNC-Hospital in 2001 Epidemiology: part of normal flora and usually only cause infection in pxs compromised by antibiotics, immunosuppresives, pregnancy, diabetes, HIV Characteristics: polysaccharide capsule Major fungal cause of meningitis, mainly of immunocompromised pxs Epidemiology: pigeon droppings Characteristics: molds with septate, hyaline hyphae and 45 dichotomous branching, no yeast phase; ubiquitous Disease: Allergic bronchopulmonary aspergillosis (ABPA) CF pxs Aspergilloma (fungus ball) TB pxs Invasive aspergillosis - fatal, multiple organ failure in immunocompromised Characteristics: common bread molds, ubiquitous; aseptate hyphae with right angle branching Disease: rhinocerebral - fatal in ketoacidotic diabetics Characteristics: only found in lung; never found in environment Disease: atypical pneumonia (PCP) only found in highly immunocompromised patients