Lecture 3 Introduction to the Actinobacteria Actinomycosis

(1)

Lecture 3

Introduction to the Actinobacteria

Actinomycosis

January 17, 2005

Lecturer: Terri McLenon

Prokaryotic species concept

Wayne et al., 1987

“a distinct genospecies that cannot be differentiated from another genospecies on the basis of any known phenotypic property not be named until it can be differentiated by some phenotypic property”

Wayne et al., 1987

Vandamme et al., 1996 “polyphasic approach”

Wayne et al., 1987

Vandamme et al., 1996 “polyphasic approach”

Rosello-Mora and Amann, 2001

(2)

Rosello-Mora and Amann, 2001

“phylo-phenetic” species concept

1. Indicate genomic boundaries of the unit

2. Describe phenotype of taxon

3. Indicate monophyletic nature of taxa

Three domains of life (Woese et al., 1990)

Carl Woese

http://www.life.uiuc.edu/micro/faculty/faculty_woese.htm

Gram-stain

Three basic types of bacterial cell wall:

1. Gram-positive 2. Gram-negative 3. Acid-fast

Gram-stain

1884 – Hans Christian Gram, a Danish bacteriologist, developed a method to differentiate bacteria into two groups, Gram-positive and Gram-negative based on the chemical and physical properties of their cell walls

(3)

Gram-stain

http://en.wikipedia.org/wiki/Image:Hans_Christian_Gram.jpg

Hans Christian Gram

4 basic steps:

1. Crystal violet basic dye 2. Grams iodine solution 3. Grams decolorizer solution 4. counterstain

Gram-stain

http://en.wikipedia.org/wiki/Image:Hans_Christian_Gram.jpg

Actinomyces bovis Gram-positive Hans Christian Gram

Gram-stain

Gram-positive bacteria Ex. “Actinomycetes”

• Less severe disease organisms

• Human body produces lysozyme that breaks down exposed peptidoglycan cell wall

• More susceptible to beta-lactam antibiotics Ex. Penicillin

Gram-stain

Gram-positive bacteria Ex. “Actinomycetes”

• Less severe disease organisms

• Human body produces lysozyme that breaks down exposed peptidoglycan cell wall

• More susceptible to beta-lactam antibiotics Ex. Penicillin

Gram-negative bacteria

• Generally, more virulent pathogens because outer membrane hidden in slime layer (capsule) which hides antigens of cell host immune system • Lipopolysaccharides in the outer membrane is an endotoxin and increases the severity of inflammation

• Semipermeable outer membrane may prevent some toxic substances from entering the bacterium

Ex. Penicillin and lysozyme

(4)

Gr. Actis

Gr. Actinis = a ray, beam

Gr. Bakterion = a small rod

Formerly known as “Actinomycetes”

Ecology: • Found in soil

• Involved in decomposition • Some inhabit plans and animals • A few pathogens

Actinobacteria Actinomycosis: Definition

Clinical entity consisting of a chronic suppurativeand granulomatous

disease characterized by peripheral spread and extension to contiguous tissue, rare hematogenous spread, and the formation of multiple draining sinus tracts.

Sinuses drain from suppurative pyogenic lesions. Exudate contains firm, lobulatedgrainsor microcolonies of the etiologic agent and adherent cellular debris, associated microorganisms, and coccoid or bacillary forms of the etiologic agent.

Normally affects the cervicofacial, thoracic, and abdominalregions in man and may result in severe disfigurement and disability. Localized lesions are amenable to therapy, but cases of extensive involvement or hematogenous spread are fatal. Able to invade and destroy bone. Localized infections without granules and sinus tracts may be chronic and weakly invasive. Otherwise may be fulminant and rapidly fatal.

Synonomy = Lumpy jaw, leptothricosis, streptotricosis

(Rippon, 1988)

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.1883 Actinomycosis: Three major forms

1826 – Leblanc described actinomycotic tumors in cattle but incorrectly called them “osteosarcomas”

1845 – Langenbeck described disease in humans, but not published until 40 yrs later

1857 – Lebert first published clinical description of the disease entity

1876 – Bollinger recognized actinomycosis as a specific parasitic disease, “lumpy jaw disease of cattle”

1877 – Harz confirmed existence of ray-likeorganism he named Actinomyces bovis

1878 – Israel and Ponfick described presence of granules in human autopsy material that resembled

granulesfound in cattle

1890 – Bostroem incorrectly hypothesized that actinomycosis was trasmitted exogenously via chewing straw

1891 – Wolf and Israel isolated the organism in human carriers and cultured anaerobic filamentous organisms from human clinical material

1910 – Lord’s invitro work showed that actinomycosis was endogenousto humans in tonsillar crypts, named Actinomyces israelii

~1940 – extensive work by Emmons, Rosebry, Thompson, Pine, Erikson, and Reich confirmed that whereas A. bovisresulted in the bovine infections, A. israeliiwas responsible for human disease

(5)

Actinomycosis: Epidemiology

Rare disease, world wide reports

Lowering incidence -antibiotics

-improved oral hygiene

Male:Female ratio* 3:1 or 4:1

Actinomycosis: Cervicofacial

(Miller and Haddad, 1998)

Actinomycosis: Pathogenesis

Family: Actinomycetaceae = “Actinomycetes” Genus: Actinomyces

Species: A. israelii(man) Species: A. neaeslundii Species: A. viscosus(man) Species: A. odontolyticus Species: A. bovis(animals) Species: A. baudetii(cats and dogs) Genus: Arachnia

Species: A. propionica Suborder: Micrococcineae Genus: Bifidobacterium

Species: B. dentium (Stackebrandt et al., 1997) (Rippon, 1988)

Classification of etiologic agents

Endogenous commensals

Not found in soil

Rarity of infection, low potential for virulence/invasion

(6)

(Schaal and Lee, 1992)

Non-specific cellular defense:

•Neutrophils

• phagocytosis • cell death

• release of cellular materials into tissue “pus”

Inflammation

•Granulomasare most common in diseases in which the body's

defenses, unable to destroy the offending organisms, try to enclose them in a mass of inflammatory cells.

(7)

Actinomycosis: Histology

Actinomyces israeliiin lung tissue (Rippon, 1988) “ray-like” appearance

of granule

Multiple grains _{(Rippon, 1988)}

granule

“clubs” with attached neutrophils

Actinomycosis, a pathologic condition that has both granulomatous and suppurative features, most often presents itself in two clinical forms:

1. Chronic, slowly progressive and indolent with indurated infiltration and multiple abscesses and fistulas. Persistent swelling can be present for weeks, months, or even years. Hard, boardlike lesion has lumpy appearance.

2. Acute and rapidly progressive with fever and a sore, fluctuating swelling that cause it to resemble a typical pyogenic infection.

Actinomycosis is often considered an affliction of soft tissues, but in fact the process spreads to bone in up to 15% of cases.

Actinomycosis: Clinical manifestation

(8)

Actinomycosis – Clinical manifestation

Cervicofacial

Early lesion on jaw: Erythematous swelling Nodules is hard and palpable

(Rippon, 1988)

Cervicofacial

Developing lesions: Hard masses soften Abscesses & granulomata

Sinus tracts discharge purulent material containing sulfur granules (Rippon, 1988)

Cervicofacial

Later in disease: Periostitis develops

Etiologic agent can burrow through bony material

(9)

Actinomycosis: Diagnosis

Actinomycosis can resemble a multitude of pathologies, ranging from benign infection to metastatic tumor. Referred to as the “chameleon of head and neck pathology.”

Absolute identification is done by anaerobic culture, biochemical tests, and gas chromatography.

Actinomycosis: Diagnosis

Actinomycosis can resemble a multitude of pathologies, ranging from benign infection to metastatic tumor. Referred to as the “chameleon of head and neck pathology.”

Absolute identification is done by anaerobic culture, biochemical tests, and gas chromatography.

Cultured in <50% of cases and often misdiagnosed. Probably due to: 1) lack of communication between the clinician and the laboratory resulting in improper culturing techniques,

2) overgrowth by other types of bacteria, and

3) previous antibiotic regimens alter oxidoreduction potential and impede Actinomyces growth.

In the absence of absolute bacterial identification from culture, diagnosis is usually based on strong presumption from clinical presentation and histologic findings.

Actinomycosis: Treatment

Before antibiotic treatments were introduced, prognosis associated with actinomycosis was poor.

1938 – sulfonamides

1948 – Nichols and Herrell pioneered the use of penicillin and has remained the treatment of choice since then

Treatment is centered on surgical manipulations and high-dose long-term antibiotic treatment.

Actinomycosis: Treatment

(Miller and Haddad, 1998) Other antibiotics that can be used when allergy to penicillin is present include erythromycin, tetracycline, clindamycin, rifampin, chloramphenicol, streptomycin, first-generation cephalosporins, imipenem, incomycin, and ampicillin.

(10)

Actinomycosis - Overview

A rare, chronic infection caused by actinomycetes bacteria and resulting in diseases of the chest, mouth and jaw, and pelvis. Symptoms may include chest pain, lethargy, weight loss, fever, draining sinuses, coughing up sputum, night sweats, and shortness of breath.

Causes, diagnosis, and treatment:

The bacteria that cause actinomycosis are normally found in the mouth and gastrointestinal tract. Poor dental hygiene and dental abscesses may produce the infection in the mouth and jaw and cause facial lesions. When the infection occurs in the chest, it produces lesions and fluid in the lungs.

The infection is diagnosed by chest X rays, tissue cultures, and bronchoscopy. Actinomycosis is treated by prolonged therapy with penicillin or another antibiotic. The infection is usually cured with antibiotics and occasionally surgery to remove lesions and drain fluid from the lungs. Prompt and thorough treatment is essential: complications from actinomycosis include brain abscess and meningitis.

(Leikin and Lipsky, 2003)

Supplementary reading

Rippon (1988)

Chapter 2 - Actinomycosis

Schaal KP and Lee HJ. 1992. Actinomycete infections in humans – a review. Gene, 115: 201.