Bartonella species share several general characteristics. Members of the genus are small (approximately 0.3 μm × 1 μm), Gram-negative, pleomorphic — meaning variable in shape — coccobacilli. These bacteria are facultative intracellular pathogens, many of which use hemotropism (infection of red blood cells) as a parasitic strategy. All members of the genus are notoriously fastidious and grow slowly in vitro. It has been shown that Bartonella species infect a wide range of mammalian hosts, and at least three species (B. bacilliformis, B. henselae és 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.

Transmission of Bartonella to humans occurs in most cases through insect vectors. The list of vectors associated with transmission includes flies, fleas, ticks, lice, and mites. It has been suggested that B. henselae may also spread directly and mechanically from cats to humans, resulting in the so-called “cat scratch disease.” The role of the cat flea in this process appears likely and may involve contamination of cat claws with infected flea feces.

Isolation of Bartonella spp. from clinical samples requires a longer incubation period and special culture media.

Bartonella bacilliformis produces an extracellular protein called “deformin,” which alone is capable of creating indentations and grooves in red blood cell membranes.

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

Certain Bartonella species produce hemolysins — extracellular proteins that cause partial or complete beta-hemolysis — leading to the breakdown of red blood cells, which can result in severe anemia.

The three main human-pathogenic Bartonella species produce a protein that stimulates angiogenesis and likely facilitates the development of vascular lesions during infection.

Hemotropism is a striking aspect of the physiology of most Bartonella species, providing ideal living conditions. Many pathogenic bacteria use heme uptake as a mechanism 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.

Bartonella species have developed various strategies to evade detection and destruction by the host’s immune system, ensuring their survival and replication within the host. Following infection, Bartonella alters the immunogenic proteins on its surface to avoid immune recognition through antigenic or phase variation. The diverse lipopolysaccharide structures of certain Bartonella species enable them to escape detection by the host’s pattern recognition receptors. Moreover, their ability to survive within mature red blood cells and resist lysosomal fusion further complicates immune clearance. Some Bartonella species also avoid immune attacks by forming biofilms, producing anti-inflammatory cytokines, and 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.

Certain strains of B. henselae exhibit significant gene rearrangements and DNA amplification due to genetic variation; therefore, DNA-based tests do not always yield positive results.

The clinical presentation of Bartonella infection ranges from relatively mild lymphadenopathy and other minor symptoms, such as cat scratch disease, to life-threatening systemic illness in immunocompromised patients. In some individuals, proliferation of endothelial cells and neovascularization are observed — a unique pathogenic process characteristic of bacteria from this genus. As the spectrum of diseases attributed to Bartonella continues to be refined, the demand for reliable laboratory methods to diagnose infections caused by these unique organisms is also increasing.

              a                                          b                                               c

4. ábra. Bartonella-fertőzés sötétlátóteres mikroszkópos képe emberi vörösvértestekben (a-b) és emberi fehérvérsejtekben (c)

Due to the variable genetic profile of Bartonella species and the limited knowledge about other human-pathogenic Bartonella strains, morphological examinations performed using dark-field 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.

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