Bacteriology exam prep: Intracellular Bacteria: Chlamydiaceae, Coxiella, Rickettsiales, Anaplasma, Ehrlichia, Lawsonia intracellularis

Chlamydia

• Chlamydiaceae are globally recognized as important veterinary and human pathogens, infecting a wide range of hosts, including humans.
• They are obligate, intracellular pathogenic bacteria that survive and multiply only inside a host cell.
• They are Gram-negative, but lack the typical peptidoglycan layer found in most bacterial cell walls.
• The cell envelope is composed of proteins and lipopolysaccharides.
• Chlamydia spp. cannot be cultivated with standard laboratory methods and require special stains like Giemsa or other polychromatic stains.

Genus Chlamydia

• There are 15 characterized species of Chlamydia.
• Almost all members are globally recognized as major veterinary pathogens, with several spilling over to humans.
• Five major pathogens are: Chlamydia psittaci, Chlamydia abortus, Chlamydia pecorum, Chlamydia trachomatis (human pathogen), and Chlamydia pneumoniae (human pathogen).

Infections and Transmission

• Chlamydia infections are intracellular and do not have a free-living or environmental reservoir.
• They cannot survive outside of the host cell for extended periods.
• Infections occur in target tissue and cause diseases similar to Mycoplasma species.
• Natural habitat is the gastrointestinal tract, with continuous fecal shedding.
• Transmission occurs through the fecal-oral route, inhalation of droplets, and interpersonal contact.

Life Cycle

• The life cycle is biphasic, alternating between the elementary body (infectious form) and the reticulate body (replicating form).
• The cycle begins with attachment and entry of the elementary body into the host cell.
• Inside the cell, the elementary body differentiates into a reticulate body, which replicates by binary fission.
• The reticulate body then differentiates back into an elementary body, which is released to infect neighboring cells.

Virulence Factors and Pathogenesis

• The most important virulence factor is the Type III Secretion System (T3SS).
• T3SS allows for effector protein translocation into host cells, manipulating the inclusion vacuole.
• Effector proteins target the host cell's nuclear membrane, impacting apoptosis and promoting host cell survival.
• Chlamydia exits the host cell by lysis or the extrusion of the inclusion vacuole, causing tissue damage.

Pathogenic Species and Caused Diseases

• Chlamydia abortus causes enzootic abortion in ewes, an economically important disease in sheep.
• Infections can remain latent and asymptomatic until pregnancy, when the organism invades the placenta and causes abortion.
• The disease can result in "storms of abortion" when new introductions or primiparous ewes enter the flock.
• C. abortus infections also occur in cattle, pigs, deer, horses, and other animals, and present a zoonotic risk to humans, particularly pregnant women.

Chlamydia psittaci

• Avian chlamydial infections and disease are primarily caused by C. psittaci, but other avian species also have pathogenic potential.
• C. psittaci is globally disseminated with a broad avian host range, infecting over 500 avian species, with highest prevalence in pigeons and psittacine birds.
• In avian hosts, C. psittaci infections may vary from subclinical with persistent organism shedding to severe acute disease.
• Disease presentations in affected birds include wasting, lethargy, air sacculitis, hepatitis, pericarditis, conjunctivitis, and respiratory symptoms.

Chlamydia felis

• C. felis is an important pathogen causing acute to chronic unilateral or bilateral conjunctivitis, rhinitis, and respiratory disease in cats.
• Bacterial transmission between cats typically occurs by direct contact of infectious materials, particularly ocular and oronasal secretions.
• C. felis primarily infects the conjunctival epithelium and causes acute to chronic or recurrent mucoid/mucopurulent to follicular conjunctivitis and rhinitis.

Coxiella burnetii

• C. burnetii is a gram-negative obligate intracellular pathogenic bacterium, which causes coxiellosis or Q fever.
• In animals, C. burnetii is a significant cause of abortion and reduced reproductive capacity, which is also an important zoonotic concern.
• C. burnetii causes a zoonotic human infection termed Q fever, with a worldwide distribution and found in a wide array of domesticated and wild animals.
• Transmission occurs through ticks, inhalation of contaminated aerosols, and aerosol transmission.
• C. burnetii has a biphasic developmental lifecycle involving two morphological forms: the replicative large-cell variant (LCV) and the metabolically dormant, spore-like small cell variant (SCV).
• SCV are internalized and converted to LCV in about two days, with exponential replication of LCVs occurring around four days post-infection.
• C. burnetii survives a degradative lysosomal environment and requires it to initiate intracellular replication.

Rickettsiales

• The order Rickettsiales is composed of two families: Anaplasmataceae (Anaplasma, Ehrlichia, Neorickettsia) and Rickettsiaceae (Rickettsia).
• Rickettsiales are gram-negative, obligately intracellular bacteria transmitted by arthropod vectors.
• They cause many important life-threatening infections in livestock and companion animals and emerging zoonoses in humans.

Anaplasma

• Anaplasma species cause severe diseases in animals, which can also be potentially fatal.
• They trigger immune activation leading to hypersensitivity reactions and impair host defense mechanisms.
• Anaplasma species mostly infect blood cells, erythrocytes, neutrophils, or platelets, and severely impair host defense mechanisms.
• They replicate by binary fission within the phagosome of an infected eukaryotic cell, requiring host nutrient support.
• All known pathogenic Anaplasma species are transmitted by ixodidae hard ticks.
• Anaplasma species have surface-expressed proteins that function as adhesion molecules.
• Once inside a cell, anaplasmas alter post-translation protein modifications and gene expression to support their growth and replication.

Anaplasma Species

• Anaplasma marginale and A. centrale are primary pathogens of cattle, infecting erythrocytes and causing bovine anaplasmosis.
• A. ovis infects erythrocytes and causes ovine anaplasmosis.
• A. phagocytophilum infects granulocytes in various vertebrates, including cattle, horses, dogs, cats, and humans, causing diseases such as equine anaplasmosis, bovine granulocytic anaplasmosis, and human granulocytic anaplasmosis.
• A. platys infects thrombocytes and causes cyclic thrombocytopenia in canines.

Anaplasma marginale (Bovine Anaplasmosis)

• A. marginale is a major economically important disease of cattle in the US and worldwide, causing mortality and morbidity.
• The pathogen is maintained in infected hosts, which also act as reservoirs of infection.
• Diverse clinical manifestations occur, including anemia, fever, increased heartbeat, anorexia, depression, constipation, abortion, muscle weakness, myocardial hypoxia, and diarrhea.
• In severe cases, animals may exhibit spikes of fever, lethargy, inappetence, pale mucous membranes, anemia, and jaundice, and may progress to a fatal outcome.
• The clinical disease spectrum varies depending on the age of animals and strain of the pathogen.

Anaplasma phagocytophilum

• A. phagocytophilum infects a wide range of hosts, including horses, cattle, humans, dogs, and cats.
• Infections are primarily reported in the US, Europe, and East Asia.
• The disease is transmitted by ticks, such as Ixodes scapularis, I. pacificus, I. ricinus, and I. persulcatus, and the primary vertebrate reservoir is the white-footed mouse (Peromyscus leucopus).
• Clinical symptoms include fever, depression, increased heart rate, decline of appetite, anemia, icterus, and ataxia, with ataxia more common in horses.

Anaplasma platys

• A. platys primarily infects canines, causing cyclic thrombocytopenia.
• Infections are documented globally, and the tick vector is likely the brown dog tick (Rhipicephalus sanguineus).
• Clinical signs include fever, anorexia, weakness, anemia, lethargy, eye discharge, spot hemorrhage on the eye, oral mucosa, and skin, respiratory distress, lymphadenomegaly, epistaxis, splenomegaly, and muzzle hyperkeratosis.

Ehrlichia

• Ehrlichia species are tick-transmitted, obligately intracellular bacteria, and are etiologic agents of important veterinary diseases, such as canine monocytic ehrlichiosis (CME).
• Ehrlichia spp. are transmitted by ticks, including Amblyomma, Dermacentor, Ixodes, and Rhipicephalus spp.
• Ehrlichia spp. infect mononuclear phagocytes in dogs, replicating in membrane-bound vacuoles forming microcolonies (morulae).
• The clinical course of E. canis infection has been well documented, consisting of acute, subclinical, and chronic phases.

Rickettsia

• Rickettsia species are obligately intracellular organisms, including pathogens that are transmitted by ticks, fleas, mites, and lice.
• Rickettsia rickettsii, R. conorii, R. typhi, R. prowazekii, and R. africae are known to infect animal reservoirs, but only R. rickettsii, R. typhi, and R. conorii have been well documented to cause clinical disease in dogs.
• Rickettsia rickettsii is highly pathogenic for some inbred breeds of dogs and can reside in a zoonotic cycle involving dogs and the brown dog tick (Rhipicephalus sanguineus) or Amblyomma aureolatum.
• Clinical manifestations of R. rickettsii infection in dogs include fever, depression, anorexia, lymph node enlargement, subcutaneous edema, muscle and joint pain, and petechiation of the skin and mucous membranes.

Lawsonia intracellularis

• Lawsonia intracellularis is the sole species in the genus Lawsonia, and is the etiologic agent of proliferative enteropathy, an infectious, intestinal hyperplastic disease.
• L. intracellularis is a small, gram-negative, obligately intracellular, curved-shaped bacterium found in the apical cytoplasm of infected enterocytes.
• The disease has been reported in a broad range of hosts, including pigs, non-human primates, hamsters, rabbits, rats, guinea pigs, foals, sheep, white-tailed deer, ferrets, arctic foxes, dogs, and certain birds.
• The source of infection for these animal species has not been determined, but it may be endemic in certain species, or present in the environment.