MISCELLANEOUS GRAM-NEGATIVE BACILLI BordetellaWhooping cough FranciscellaTularemia BrucellaBrucellosis LegionellaLegionellosis.

MISCELLANEOUS GRAM-NEGATIVE BACILLI

Bordetella Whooping cough

Franciscella Tularemia

Brucella Brucellosis

Legionella Legionellosis

MISCELLANEOUS GRAM-NEGATIVE BACILLI

Bacteroides Intraabdominal infections

Fusobacterium Pleuropulmonary & CNS Infect.

Cardiobacterium Endocarditis

Eikenella Meningitis, endocarditis

Bordetella pertussis

Strictly aerobic bacilli

Transmitted by airborne droplets

Causes pertussis, or whooping cough

Binds to ciliated epithelial cells, proliferates, causes tissue damage

Bordetella pertussis

Pertussis toxinADP-ribosylates guanine nucleotide-binding proteins at the cell membraneInterferes with signal transduction by chemokine receptors

lymphocytes unable to enter lymphoid tissue increase in lymphocytes in the blood

(lymphocytosis)Mediates binding of the bacterium to ciliated cells

Adenylate cyclaseGuanine nucleotide-binding regulatory protein (stimulatory)

Guanine nucleotide-binding regulatory protein (inhibitory)

Pertussis toxin inactivates the inhibitory Gi protein

Bordetella pertussis

Adenylate cyclase toxin inhibitsleukocyte chemotaxis, phagocytosis and killingoxidative activity of alveolar macrophagescell lysis by NK cells

Tracheal cytotoxin inhibitsciliary movement in epithelial cells (ciliostasis)DNA synthesis

Bordetella pertussis

Filamentous hemagglutinin and Pertactin (P69 protein; 69kD) mediate attachment of B. pertussis to ciliated cells

Arginine-Glycine-Aspartic acid (RGD) sequence on these adhesins facilitates binding to glycoprotein integrins on ciliated respiratory cells

Bind to complement receptor 3 (CR3) on macrophages and facilitate phagocytosis

Bordetella pertussis

Catarrhal stage7-10 days after infectionresembles a common cold highest risk for transmission

production of bacteria is at a peak disease is not recognized as pertussis

Bordetella pertussis

Paroxysmal stage 1-2 weeks after the onset of the catarrhal stage repetitive coughs followed by an inspiratory whoop paroxysms end with vomiting and exhaustion

Bordetella pertussis

Convalescent stagediminished paroxysmal coughsecondary complications

pneumoniaencephalopathyseizures

Bordetella pertussis

B. pertussis constitutes a potential health hazard to pediatricians and dental professionals treating children

Age distribution for pertussis infections

1988

1998

Incidence of pertussis in the US

Bordetella pertussis

Treatment is supportiveErythromycin

Useful in prevention of disease in exposed, unimmunized individuals

Should be given to immunized children younger than 4 years who have been exposed(since vaccine-induced immunity is not fully

protective)

Bordetella pertussis

Fears of vaccine-related toxicityencephalopathy in 1/106 cases

Acellular vaccine composed of five antigens purified from the organism (inactivated pertussis toxin via 2 amino acid changes that eliminate its ADP-ribosylating activity but retains its antigenicity)

Combined with diphtheria and tetanus toxoids in 3 doses beginning at 2 months of age

Francisella tularensis

Very small (0.2 x 0.2-0.7 µm) coccobacillus

Survives in macrophages of the RESNot affected by humoral immunity

Causes tularemia (glandular fever, rabbit fever, tick fever)

Pathogenic strains have an anti-phagocytic capsule

Francisella tularensis

Very small (0.2 x 0.2-0.7 µm) coccobacillus

Survives in macrophages of the RESNot affected by humoral immunity

Causes tularemia (glandular fever, rabbit fever, tick fever)

Pathogenic strains have an anti-phagocytic capsule

Francisella tularensis

Spreads viatick bitescontact with an infected animalconsuming infected meat or waterinhalation of infected aerosols.

Highly infectiousExposure to 10 organisms by a tick bite, or 50 by aerosol can cause disease

Francisella tularensis

Abrupt onset of fever, chills, malaise and fatigue

Most common type is ulceroglandular, with skin ulcers and lymphadenopathy

Can be treated with streptomycin or gentamicin

Brucella

Small (0.5 x 0.6-1.5 µm), non-motile, non-encapsulated, strictly aerobic coccobacilli

”Biovars" of the species B. melitensis cause human brucellosis or undulent fever (Bang's disease)

Reside in the RES, and are sheltered from human immunity

Inhibit PMN degranulation

Transmitted to humans who have direct contact with animals or who consume unpasteurized milk or cheese

Initial subacute manifestations are malaise, chills, myalgias, arthralgias and non-productive cough

Fever is common and undulant (intermittent)

Granulomas in the liver, spleen and bone marrow; enlargement of the liver, spleen and lymph nodes

Brucella

Incidence of bucellosis in the US from 1975 to 1998

Doxycycline

Doxycycline plus rifampin

Trimethoprim-sulfamethoxazolePregnant womenChildren under 8 years

Brucella

0.3-0.9 µm x 2-5 µmAerobic Appear as coccobacilli in tissuesFilamentous structures in culture

Legionella pneumophila detected only in 1976(does not stain well and does not grow on conventional media)

Legionella

Legionella pneumophila grown on charcoal-yeast extract agar

C3b binds porin and facilitates uptake via CR3 complement receptor into alveolar macrophages

Inhibit phagosome-lysosome fusion

Tissue destruction due to the production of proteolytic enzymes, phosphatase, lipase and nuclease

Seen most often in individuals with compromised immune systems or pulmonary function

Legionella

Activated macrophages

No bacterial multiplication

Resting macrophages

Multiplying Legionella

Opsonization

Found in lakes, streams, air conditioning cooling towers and potable water systems (including dental unit water-lines)

Grow on dead organic matter (saprophytes)

Legionella

Legionnaire's disease

Abrupt onset of fever, chills, headache and non-productive cough A multi-organ disease, with abnormalities in the GI tract, CNS, liver and kidneys

Pulmonary function deteriorates if not treated

Legionella

Direct fluorescent antibody stain of Legionella

The most sensitive method to detect the bacterium

Prevention

Reduce the microbial burden in the environmental sourcehyperchlorinationelevated temperatures(only moderately successful)

Legionella

Treatment

Macrolides: Erythromycin, azithromycin or clarithromycinQuinolones: Levofloxacin or gatifloxacinDoxycycline

ß-lactam antibiotics are ineffective because most strains produce ß-lactamases

Aminoglycosides, penicillins and cephalosporins cannot penetrate host cells, hence are ineffective

Legionella

Obligate anaerobic bacilli that colonize the oropharynx, GI tract and genital tract

The most common cause of serious anaerobic infections such as sepsis, peritonitis and abscesses

Its lipopolysaccharide has no endotoxin activityNo phosphate on lipid AFewer fatty acids

Bacteroides

Bacteroides fragilis

Pleomorphic,faintly staining,Gram-negative rods

B. melaninogenicus sub-species asaccharolyticus have been re-classified and include

Porphyromonas gingivalis (prominent in patients with periodontal disease)

Porphyromonas endodontalis (isolated from infected root canals in humans)

Bacteroides

Bacteroides fragilis constitutes only 1-2% of intestinal flora, but is the major cause of intraabdominal infections

The capsule prevents phagocytosis, and promotes abscess formation

Capsules mediate adhesion to peritoneal surfaces

Collagenase, hyaluronidase, neuraminidase, cause tissue destruction and IgG protease inactivates immunoglobulins

Bacteroides

Strains of Bacteroides fragilis that cause diarrheal disease (“enterotoxigenic” strains) produce a zinc metalloprotease

Causes F-actin rearrangement in intestinal epithelium

Resulting in chloride secretion & fluid loss

Bacteroides

B. fragilis is isolated invirtually all abdominal infectionsmore than 67% of suppurative (pus-forming) pelvic

infections15-20% of pleuropulmonary infections

B. melaninogenicus group is common in pleuropulmonary and CNS infections

Bacteroides

Treatment

Metronidazole (Flagyl)

Carbapenems (e.g. imipenem),

Resistance to clindamycin and tetracycline has developed in B. fragilis (mediated by transferrable plasmids)

Bacteroides

Fusobacterium is fusiform (spindle-shaped)

Fusobacterium

Fusobacterium nucleatum

LPS stimulates leukocyte chemotaxis by activating the alternate pathway of complement (via C5a)

Fusobacterium are common in pleuropulmonary and CNS infections

Wolinella is a fusobacterium that populates the oropharynx

Fusobacterium

C. hominis is present in the respiratory tract of about 70% of healthy individuals

Most patients who develop C. hominis endocarditis have a history of dental disease or dental procedures before clinical symptoms developed, and pre-existing heart disease

Cardiobacterium

Enters the bloodstream from the oropharynx, adheres to the damaged heart tissue, and multiplies.

Complete recovery following appropriate antibiotic therapy (penicillin or ampicillin for 2-6 weeks)

Cardiobacterium

E. corrodens "corrodes" or form pits in agar

Facultatively anaerobic, gram-negative bacillus

A normal resident of the upper respiratory tract

Opportunistic pathogen: causes infections in immunocompromised patients and in patients with diseases or trauma to the oral cavity

Causes sinusitis, meningitis, brain abscesses, pneumonia, lung abscesses, and endocarditis

Eikenella