Bartonella quintana

From MicrobeWiki, the student-edited microbiology resource

A Microbial Biorealm page on the genus Bartonella quintana

Classification

Gram-negative rod shape

Higher order taxa

Domain:Bacteria, Phylum: Proteobacteria, Class: Alpha Proteobacteria, Order: Rhizobiales, Family: Bartonellacaea

Edited by Rani Thamawatanakul, student of Rachel Larsen at UCSD.

Genus

Genus species: Bartonella Quintana


NCBI: Taxonomy

Edited by Rani Thamawatankul, student of Rachel Larsen at UCSD.

Description and significance

Bartonella quintana was formally classified in the Rickettsiaceae family as the obligately intracellular (cannot reproduce outside the host cell) Rochalimaea quintana (28). The difference between Rickettsia and Rochalimaea was the chemical composition in their genomic structure. Rickettsia species have a low level of guanine and cytosine (28.5 – 33.3 mol%) but Rochalimaea and Bartonella species have a higher level (39.0 – 40.0 mol%). The description of these species has increased by the availability of modern taxonomic methods. Few techniques would include DNA hybridization and 16 rRNA gene sequence comparison (4).

B. quintana as opposed to related species, B. bacilliformis and B. clarrideiae that posses flagella uses a twitching movement caused by fimbriae. B.quintana is a facultative, Gram-negative bacilli belonging to 2 subgroup of proteobacteria. The dimensions of the bacterium is 0.3 – 0,5 m wide and 1-1.7 m long (7). It can be cultured in media containing blood or hemin and in a moist 5-10% carbon dioxide atmosphere at 30C to 37C (5). Because B. quintana is a slow-growing bacterium, primary isolations are available 12 to 14 days after B. quintana has been embedded and incubated in blood agar at 37C. Unfortunately, incubation periods could last as long as 45 days that is necessary for primary isolations (3).

Humans are the reservoir of the bacterium but the mode of transmission comes directly from a human body louse, Pediculus humanus corporis (20). During asymptomatic period, B. quintana is located in the erythrocytes and has been detected in erythroblasts at the bone marrow (12). Also, bacillary angiomatosis infection is caused by B. quintana having an affinity for endothelial cells, leading to angioproliferative lesions (13).

Currently, B. quintana is unique among bacterial pathogens it has reemerged as an opportunistic infectious agent primarily in immunocompromised patients, especially individuals suffering with HIV infection. It also causes a febrile disease among alcoholic individuals and the homeless populations in the cities in United States and Europe called “urban trench fever” (11). B. quintana infections can manifest as bacillary angiomatosis, bacillary peliosis, endocarditis, and chronic bacteremia, which could be life-threatening if these conditions occurred concurrently (7).

Edited by Rani Thamawatankul, student of Rachel Larsen at UCSD.

Genome structure

B. quintana’s genome is composed of a single circular chromosome containing 1,581,384 bp. In addition, 1,308 genes that have been identified only but 26 genes are unique to B. quintana. It has been recently discovered that the genome sequence of B. quintana is a derivative of the larger 1.9 Mb genome of B. henselae. B. quintana does not contain genomic islands coding for filamentous hemgglutinin found in B. henselae (14). Southern blots indicated that all five pathogenic Bartonella spp. posses hbpA homlogs, which encodes an integral membrane protein localized at the outer membrane and surface exposed. HbpA is the first potential virulence determinant characterized from B. quintana (18). In addition, both B. quintana and B. henselae genomes are shortened versions of chromosome 1 from the highly related pathogen Brucella melitensis (14).

Edited by Rani Thamawatankul, student of Rachel Larsen at UCSD.

Cell structure and metabolism

A number of bacterial pathogens have evolved for accumulating hemin in order to satisfy their iron, proporphyrin ring, or cytcochrome cofactor requirements. However, early studies with B. quintana indicated that iron is the critical component provided by hemin supplements (15). The transport of iron from hemin is a TonB-dependent process that requires the synthesis of a surface-membrane receptor to facilitate the binding of the ligand. Next, a protein in the periplasmic space transports the hemin to the cytoplasmic membrane, and finally a permease brings the molecule into the bacterial cell (16).

In early 1960’s, Vinson first cultured B. quintana in axenic media, either in blood–enriched agar or in broth with amino acids, yeast extract, and fetal bovine serum (2). These microorganisms obtain their source of energy from succinate, pyruvate, and glutamate but unable to use glucose. In addition, bicarbonate is essential for B. quintana as a source of carbon dioxide (1). Because Bartonella spp. are the only bacterial pathogens that engage in hemotrophy (erythrocyte parasitism), all Bartonella species require erythrocytes or hemin supplements in order to grow in vitro. B. quintana has the highest hemin requirement (20 to 40 µg/ml of medium) for a bacterium (15). There is a family of hemin binding proteins (HbpA, HbpB, HbpC, HbpD, and HbpE) that is synthesized by B. quintana and is served as hemin receptors (18). However, the reason for this unique characterization of B. quintana hemin requirement and mechanism is still unclear. Although HbpA plays a role in the ability of B. quintana to acquire hemin from the environment (abiotic or biotic), antibiotics specific for HbpA may inhibit the ligand-receptor interaction (17). Because HbpA is only one of the eight membrane-associated proteins in the organism, hemin binding is not abolished in the presence of anti-HbpA Fab fragments. The exact localization and involvement in iron acquisition of the additional hemin-binding membrane proteins is currently under investigation (18).

Pili and specialized extensions of the outer membrane are thought to play an important role in adhesin to nucleated cells. Pili structures in B. henselae, B. quintana, B. tribocorum, and B. alsatica posses type IV pili. Twitching motility and self-aggregation are specific properties typical for this type of pili (19).

Edited by Rani Thamawatankul, student of Rachel Larsen at UCSD.

Ecology

Since B. quintana is able to produce a variety of disease, it must be able to adapt, survive and replicate in different environments of the Pediculus humanus coproris gut and the human immune system. A recent study by Minnick examined environmental factors (heme, oxgen, and temperature) that regulate transcription, regulation, and synthesis of the virulence factor (Hbps) of B. quintana. First, hbpC expression is regulated temperature. In effect, HbpC synthesis is greatest at cooler body temperature of the body louse. Second, the cultivation of the bacterium in human bloodstream oxygen concentration decreases the expression of all hpb genes. Minnick indicated that synthesis of HbpC is influenced by oxygen (5% relative to 21% atmospheric) and/or reactive oxygen species. Third, different expression patterns of hbp had different effects when grown in a range of hemin concentrations. A high heme concentration stimulates expression of hbpC and hbpB and a low heme concentration stimulates expression of hbpA, hbpD, hbpE. It’s been considered that the high hemin requirement is essential for replication to maintain pathogenic property of B. quintana (21).

Pathology

B. quintana is identified as a bacterial agent of trench fever that infected more than one million troops and prisoners living in crowded, unhygienic conditions in the First World War (8). By 1915, the human body louse was recognized as the insect vector of B. quintana through experimentations on volunteer soldiers (6). People are infected by inoculation of the organism in louse feces through a break in the skin, either from the bite of the louse or other means. Infected lice begin to excrete infectious feces 5-12 days after ingesting infective blood, which continues throughout the remainder of their life span (29). The first experiment demonstrated volunteer soldiers contained “rickettsia bodies” in their gut when blood was transferred from trench fever patients. In the second experiment, Kosterzewski confirmed that body lice were the primary vectors of B. quintana (10). This was observed when macaque monkeys were infected after they were injected with blood from typhus patients. Therefore, the transmission of the disease between monkeys was by means of body louse, the same body louse that was found on the uniforms of soldiers infected with trench fever and typhus. Thus, an effective transmission control consisted of washing and delousing procedures (9).

Clinical manifestations of trench fever range from asymptomatic infection to severe, life-threatening illness. Few of the common symptoms include headache, pain in the legs and loins, constipation, insomnia, dyspnea, and abdominal pain. Trench fever often results in prolonged disability but no fatalities have been recorded. Patients are profoundly ill in the early state of the disease and continue for 4 to 6 weeks. A minor illness could become chronic – Byman defined chronic trench fever as “a state of marked debility, with or without attacks of slight fever and aching, and characterized by a hyperexcitability of the nervous system in general” (29). After the primary infection of trench fever resolves, chronic bacteremia develops. After 8 years of experiment, Kostrzewski confirmed that B. quintana was present in the blood of trench fever patients; therefore, persistent bacteriemia is associated with B. quintana infection (10). In addition, patients with bacillary angiomatosis and endocartisis have also reported being infected with bacteremia (30).

Bartonella are unique among bacterial pathogens in their ability to cause angioproliferative lesions, involving proliferation of endothelial cells. Immunocompromised patients are highly susceptible to bacillary angiomatosis, predominately patients with AIDS (23). B. quintana and B. henselae are the agents of bacillary angiomatosis (31). Bacillary agniomatosis often involves infection of the skin, but various organs could be affected, including the liver, spleen, bone marrow, and lymph nodes. Cutaneous lesions may be solitary or multiple; they may be superficial, dermal, or subcutaneous. Deep lesions may be red, purple, or uncolored. Deep lesions are colorless and either mobile or fixed to underlying structures (7). Subcutaneous lesions may erode into underlying bones are associated with B. quintana whereas hepatic peliosis and lymph node lesions are associated with B. henselae (31). Some of the symptoms include fever, abdominal pain, malaise, and vomiting (peliosis hepatitis).

There have been previous reported cases that B. quintana causes lymphadenoapthy. A non-HIV infected women was diagnosed with chronic cervical and mediastinal adenoapathy (3). She had an enlarged lymph node removed and samples of the blood were collected. Histological examinations of cervical lymph node and bone marrow showed a granulomatous reaction. In a recent study, an HIV-infected patient with supraclavicular inflammatory lymphadenitis had a coinfection of B.quintana and Mycobacterium tuberculosis (32).


Edited by Rani Thamawatankul, student of Rachel Larsen at UCSD.

Application to Biotechnology

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Current Research

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References

example:

Glockner, F. O., M. Kube, M. Bauer, H. Teeling, T. Lombardot, W. Ludwig, D. Gade, A. Beck, K Borzym, K Heitmann, R. Rabus, H. Schlesner, R. Amann, and R. Reinhardt. 2003. "Complete genome sequence of the marine planctomycete Pirellula sp. strain 1." Proceedings of the National Acedemy of Sciences, vol. 100, no. 14. (8298-8303)


Edited by student of Rachel Larsen and Kit Pogliano