Bartonella species share a number of common characteristics. The members of the genus are small (about 0,3 μm × 1 μm), Gram-negative, pleomorphic, i.e. coccobacilli of variable shape, showing a range of forms from round to slightly elongated, depending on the test method and medium. The bacteria are facultative intracellular pathogens, many of which employ hemotrophic (infection of red blood cells) as a parasitic strategy. All members of the genus are notoriously fastidious and slow growing in vitro. It has been shown that the Bartonella species infect a wide range of mammalian hosts, and at least three species (B. bacilliformisB. henselae and B. quintana) are relatively common human pathogens. Vector-borne transmission is another common feature within the genus. The Bartonella species are typically spread between mammalian hosts by arthropods, and each bacterial species is transmitted by a specific insect vector. The Bartonella species are present in a wide range of mammals: they infect cats, dogs, rodents, rabbits, and cattle, as well as wild animals such as wild felids (bobcats, pumas, and mountain lions), coyotes, deer, elk, and foxes.

At least three species have been identified as primary human pathogens, and four additional species — including two subspecies — have been indirectly or through case reports associated with human disease.

A Bartonella to humans is most often transmitted via an insect vector. The list of vectors associated with transmission includes flies, fleas, ticks, lice and mites. The possibility has been raised that B. henselae is transmitted directly from cats to humans by mechanical means, resulting in the so-called “cat scratch disease”. The role of cat dander in this process seems likely and may involve contamination of cat litter with infected flea droppings.

A Bartonella spp. isolation from clinical samples requires a longer incubation period and special culture medium.

A Bartonella bacilliformis (i.e. the slightly elongated, rod-shaped bacterial species of Bartonella) produces an extracellular protein called „deformin”, which can independently create indentations and grooves in red blood cell membranes.

Figure 1. Erythrocyte invaginations caused by the deformation factor (deformin) of B. bacilliformis.

Some Bartonella species produce haemolysins, extracellular proteins that cause incomplete or complete beta-haemolysis, i.e. the complete breakdown of blood cells, which can cause severe anaemia.

The three main human pathogens Bartonella species produces a protein that stimulates angiogenesis and probably facilitates the development of vascular lesions during infection.

Haemotrophy is the most Bartonella spp. is a striking aspect of the physiology of iron, which provides ideal living conditions. Heme uptake is used by many pathogenic bacteria to acquire iron.

Figure 2. Bartonella bacilliformis penetrates red blood cells and deforms the surface of their membranes.

Figure 3. Invagination of red blood cells potentially caused by Bartonella spp. in a monkey.

In addition to the invasion of red blood cells, invasion of other host cell types (epithelial and endothelial cells) has also been demonstrated in the three main human-pathogenic species.

A Bartonella species have developed specific strategies to avoid detection and degradation by the host immune system, which ensures their reproduction in the host. Following infection, the Bartonella alters the immunogenic proteins on its surface to avoid immune recognition by antigen or phase variation. Some Bartonella species' diverse lipopolysaccharide structure allows them to avoid detection by host pattern recognition receptors. Furthermore, the survival of mature red blood cells and their resistance to lysosomal fusion further complicates the immune clearance of this species. Some Bartonella species also avoid immune attacks by producing biofilms and anti-inflammatory cytokines and by reducing apoptosis of endothelial cells.

It appears that the persistent bacteremia developing within erythrocytes is a specific adaptation of Bartonella aimed at facilitating its transmission within the host species.

A B. henselae some strains show significant gene rearrangement and DNA amplification due to genetic variation, so DNA-based tests do not always give positive results.

A Bartonella The clinical presentation of infection ranges from relatively mild lymphadenopathy and other mild symptoms, cat scratch disease to life-threatening systemic disease in immunocompromised patients. In some individuals, there is proliferation of endothelial cells and neovascularisation, a unique pathogenic process specific to this genus of bacteria. As the spectrum of diseases attributed to Bartonella continues to be refined, the need for reliable laboratory methods to diagnose infections caused by these unique organisms is increasing.

   

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Figure 4. Darkfield microscopy of Bartonella infection in human red blood cells (a-b) and human white blood cells (c)

A Bartonella Due to the variable genetic profile of the species and the lack of further knowledge on human pathogenic Bartonella, morphological studies using darkfield microscopy and scanning electron microscopy remain a reliable detection method.

Other methods used to diagnose Bartonella-associated infections include histological analysis of biopsy specimens, culture of tissue samples, blood sample culture (hemoculture), and serology, although all of these may show limited efficacy in a clinical setting.

A Bartonella species detection is still based on direct rather than serological testing, because the pathogen successfully evades immune response by its intracellular parasite lifestyle. Even in cases of significant infection, however, the low number of detectable bacteria is a problem, and therefore preliminary culture or concentration/concentration of blood samples by other methods is usually recommended. In the case of breeding, it may be advisable to pre-release the bacteria hiding in the red blood cells.

Several immunofluorescence microscopy methods have been developed to detect the different Bartonella species, but these are not yet routinely used. 

Figure 5. Laser confocal microscopy image of intracellular Bartonella quintana infection labelled with specific immunofluorescent antibodies

Figure 6. Immunofluorescence microscopy image of Bartonella henselae infection labelled with specific immunofluorescent antibodies in the lymph node of a patient with „cat scratch disease”.

Figure 7. Immunofluorescence microscopy image of Bartonella henselae infection labelled with specific immunofluorescent antibodies in the blood of a naturally infected cat.

  1. M Dworkin (editor-in-chief), The Prokaryotes, A Handbook on the Biology of Bacteria, third edition, 2006
  2. Yixuan X et al. Insidious tactics: the ingenious immune evasion mechanisms of Bartonella, Virulence. 2024
  3. D H Spach, J E Koehler: Infections associated with Bartonella, Infect Dis Clin North Am, 1998
  4. Anderson BE, Neuman MA.: Bartonella spp. as emerging human pathogens, Clin Microbiol Rev., 1997
  5. Kaiser PO et al: Bartonella spp.: throwing light on uncommon human infections, Int J Med Microbiol., 2011
  6. Rolain et al: Bartonella quintana in human erythrocytes, The Lancet, 2022
  7. Rolain et al: Detection by Immunofluorescence Assay of Bartonella henselae in Lymph Nodes from Patients with Cat Scratch Disease, Clin Diagn Lab Immunol. 2003
  8. Rolain et al: Immunofluorescent Detection of IntraerythrocyticBartonella henselae in Naturally Infected Cats, Journal of Clinical Microbiology, 2001