Higher Order Taxa
Class: Alpha Proteobacteria
Family: Bartonellaceae 
Bartonella bacilliformis 
Description and significance
In the 1870s, about seven thousand workers died in Peru due to B. bacilliformis while working on train construction. It was first isolated in 1909 by Peruvian microbiologist Alberto Barton but was not identified as the cause of Oroya fever, also known as Carrión’s disease, until 1940. It is named Carrión’s disease after a medical student who risked his life for science. In 1885, Daniel Carrión was inoculated with B. bacilliformis from the lesion of a patient. Three weeks after the inoculation, he began showing symptoms of anemia and died a week later. He found that the diseases verruga peruana (Peruvian wart) and Oroya fever had the same origin .
B. bacilliformis is a Gram-negative, aerobic, pleomorphic, flagellated coccobacillus that form translucent colonies that vary from one to two millimeters in diameter. It grows at an optimum temperature of 28°C and pH of 7.8. B. bacilliformis is a specific human pathogen, and is the causative agent of a group of diseases known as bartonellosis. This strain specifically causes Carrion's disease, which is also known as Oroya fever Carrion’s disease causes severe anemia, with a fatality rate of 40-90%, and milder episodes characterized by skin lesions that have the appearance of warts . B. bacilliformis attacks the host by adhering to and entering red blood cells and endothelial cells, causing extensive deformation . It is transmitted to humans by the bite of a female sandfly, Lutzomyia verrucarum. B. bacilliformis is known to have one of the highest mortality rates of any bacterial infection even though it has a restricted geographic habitat, which is largely in Peru, Colombia and Ecuador . It may be controlled by the use of a number of antibiotics such as streptomycin, tetracycline, erythromycin, and penicillin as well as insecticides that control vector populations .
The genome for the KC583 strain of B. bacilliformis was sequenced by The Institute for Genomic Research (TIGR) and published on January 4, 2007 [2, 3]. It consists of a single, circular chromosome that is 1,445,021 base pairs in length. It encodes 1,334 genes (1,283 protein genes and 51 RNA genes) . Some of the most important genes include a flagellin gene, which produces the proteins that form the filaments in the bacterium’s flagella , and the invasion-associated locus A and B (IalAB) genes, which enable the bacterium to parasitize human erythrocytes [5, 17]. The genome is also characterized by a GC content of 38.2% . Other strains have not yet been sequenced.
Cell Structure and Metabolism
The bacterium has a Gram-negative cell wall . It falls under the category of rod-shaped bacteria, although its actual morphology is an intermediate between cocci and bacilli, earning it the term “coccobacillus” . Its flagella enable it to be highly motile, which contributes greatly to the pathogenicity of the microorganism [2, 11]. B. bacilliformis does not produce endospores .
There are 61 known metabolic pathways for B. bacilliformis. Its carbohydrate metabolism pathways include glycolysis, which converts glucose into pyruvate, and fructose metabolism, which converts fructose into dihydroxyacetone (DHAP) and glyceraldehyde. Some of its most important energy metabolism pathways are carbon fixation, in which carbon dioxide is converted into organic materials, and nitrogen metabolism, which converts molecular nitrogen into usable forms of nitrogen (ammonia, nitrate, and nitrogen dioxide). Other metabolic pathways include metabolism of lipids, nucleotide, amino acids, and vitamins .
B. bacilliformis is an obligate intracellular parasite that causes disease a bit like malaria. It has a parasitic relationship with its insect vector and human reservoir. Its limited geographic distribution is particularly mediated by the distribution of its vector, L. verrucarum (formerly known as Phlebotomus verrucarum). It is endemic to arid areas at 500 to 3,000 meters above sea level in the Peruvian Andes between central Peru and southwestern Colombia. It has also been found in Bolivia, Guatemala, Chile, and at high elevations in Colombia and Ecuador . The bacterium is found in nearly all of the erythrocytes of infected humans in the acute anemia phase of the disease and in human endothelial cells during the chronic phase. It can also be cultured in semisolid media or in embryonated eggs . It has been reported that 5-10% of individuals living in these endemic areas have the bacteria circulating in their blood .
B. bacilliformis causes bartonellosis, also called Oroya fever, Guáitira fever, verruga peruana, and Carrión’s disease. Virulence factors influencing host cell invasion include the functioning of the flagella as well as proteins, such as deformin, and invasion-associated locus A and B (ialAB) genes .
The disease begins when infected female L. verrucarum sandflies bite the human host, usually children or young adults, at sunrise or sunset when the flies feed. L. verrucarum localizes in the capillary endothelial cells, and in most cases, the infection is initially asymptomatic, so one may become infected without even initially knowing it! Generally, around 16-22 days after the sandfly bite, the acute phasic Oroya fever, characterized by fever, headache, and malaise, occurs. The bacterium enters the bloodstream, latches onto the blood cells, and eventually causes pits and invaginations to form . These invaginations cause the cells to lyse, often resulting in severe hemolytic anemia. At this acute phase, 90% of infected patients may die if left untreated . In addition, if the patient is immunocompromised, secondary diseases may occur, making matters worse.
B. bacilliformis is specifically a human pathogen. Studies using mice that were inoculated with B. bacilliformis showed no lesions, signs, or symptoms of bartonellosis. The mice were inoculated with 1.5, 3.0, or 4.5 x 108 colony-forming units of live B. bacilliformis intradermally, intranasally, subcutaneously, or intraperitoneally. There were no cultivable organisms in the spleen, liver, or lymph nodes of the mice 145 days after inoculation .
Current research is being done by the Tropical Disease Institute (TDI) at Ohio University and Centers for Disease Control and Prevention (CDC) in Atlanta. They found evidence to suggest that the disease caused by B. bacilliformis might be more prevalent in Ecuador than previously thought. They isolated B. bacilliformis from blood samples and insect vectors and cultured them. They discovered that the human blood samples contained the bacteria but did not show signs or symptoms of the disease. More tests are currently being done to investigate the seroprevalence epidemiology of B. bacilliformis infection in Ecuador .
Recent studies have also found that although B. bacilliformis has been successfully treated by a number of antibiotics, these treatments have not been entirely successful, sometimes resulting in a relapse of the disease or even complete ineffectiveness of the drugs. Ciprofloxacin-, rifampicin-, and erythromycin-resistant strains of the bacterium have been discovered. However, they have not been shown to be resistant to gentamicin or doxycycline, and for now, these antibiotics are believed to be the best methods for treatment. Further clinical research is required to support these findings .
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Edited by Sophia Lee, Jennifer Nguyen, Raisa Nguyen, and Thuy-Ngan Nguyen of Dr. Maia Larios-Sanz at the University of St. Thomas