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Bartonella (Rochalimaea) quintana causing fever and bacteremia in an immunocompromised patient with non-Hodgkin's lymphoma.

A 48-yr-old man with stage IV non-Hodgkin's lymphoma, became neutropenic following chemotherapy and developed a fever. His blood cultures were processed to enhance the yield of fastidious bacteria. A slow-growing, capnophilic Gram-negative rod was isolated. The febrile episode was treated with cefotaxime, imipenem and vancomycin and resolved. The bacterial isolate was identified as Bartonella (Rochalimaea) quintana by 16S-rDNA gene sequencing. The isolate showed 99.8% sequence homology with the type strain. This is the first isolation of Bartonella (Rochalimaea) quintana from a bacteremic patient in Australia. This bacterium is a fastidious Gram-negative rod requiring prolonged culture for its isolation. Patients with culture-negative pyrexia, especially immunocompromised patients, may need to be investigated for infection with this agent.

Bacteremia↗

Survey of the seroprevalence of Bartonella quintana in homeless people.

Trench fever is caused by Bartonella (Rochalimaea) quintana, a small gram-negative rod that is transmitted by body lice. Recently, B. quintana infections in homeless patients have been reported in the United States and Europe. From October 1993 to October 1994, the seroprevalence of antibodies to B. quintana was assessed by indirect immunofluorescence in a prospective study of 221 nonhospitalized homeless people, 43 hospitalized homeless patients (cases), 250 blood donors, and 57 hospitalized matched controls. Four (1.8%) of 221 nonhospitalized homeless people tested had titers of > 1:100. Of the 43 cases, seven (16%) had serological titers of > or = 1:100. None of the 250 serum samples from blood donors contained antibodies to B. quintana. The presence of antibodies to B. quintana in cases was significantly associated with the presence of body lice, exposure to cats, headaches, eastern European origin, and pain in the legs. This study demonstrates the presence of antibodies to B. quintana in the homeless population and should alert physicians that B. quintana might be an etiologic agent of fever in homeless patients.

Animals↗

The louse-borne human pathogen Bartonella quintana is a genomic derivative of the zoonotic agent Bartonella henselae.

We present the complete genomes of two human pathogens, Bartonella quintana (1,581,384 bp) and Bartonella henselae (1,931,047 bp). The two pathogens maintain several similarities in being transmitted by insect vectors, using mammalian reservoirs, infecting similar cell types (endothelial cells and erythrocytes) and causing vasculoproliferative changes in immunocompromised hosts. A primary difference between the two pathogens is their reservoir ecology. Whereas B. quintana is a specialist, using only the human as a reservoir, B. henselae is more promiscuous and is frequently isolated from both cats and humans. Genome comparison elucidated a high degree of overall similarity with major differences being B. henselae specific genomic islands coding for filamentous hemagglutinin, and evidence of extensive genome reduction in B. quintana, reminiscent of that found in Rickettsia prowazekii. Both genomes are reduced versions of chromosome I from the highly related pathogen Brucella melitensis. Flanked by two rRNA operons is a segment with similarity to genes located on chromosome II of B. melitensis, suggesting that it was acquired by integration of megareplicon DNA in a common ancestor of the two Bartonella species. Comparisons of the vector-host ecology of these organisms suggest that the utilization of host-restricted vectors is associated with accelerated rates of genome degradation and may explain why human pathogens transmitted by specialist vectors are outnumbered by zoonotic agents, which use vectors of broad host ranges.

Animals↗

Bartonella henselae inhibits apoptosis in Mono Mac 6 cells.

Bartonella henselae causes the vasculoproliferative disorders bacillary angiomatosis and peliosis probably resulting from the release of vasculoendothelial growth factor (VEGF) from infected epithelial or monocytic host cells. Here we demonstrate that B. henselae in addition to VEGF induction was also capable of inhibiting the endogenous sucide programme of monocytic host cells. Our results show that B. henselae inhibits pyrrolidine dithiocarbamate (PDTC)-induced apoptosis in Mono Mac 6 cells. B. henselae was observed to be present in a vacuolic compartment of Mono Mac 6 cells. Direct contact of B. henselae with Mono Mac 6 cells was crucial for inhibition of apoptosis as shown by the use of a two-chamber model. Inhibition of apoptosis was paralleled by diminished caspase-3 activity which was significantly reduced in PDTC-stimulated and B. henselae-infected cells. The anti-apoptotic effect of B. henselae was accompanied by (i) the activation of the transcription factor NF-kappaB and (ii) the induction of cellular inhibitor of apoptosis proteins-1 and -2 (cIAP-1, -2). Our results suggest a new synergistic mechanism in B. henselae pathogenicity by (i) inhibition of host cell apoptosis via activation of NF-kappaB and (ii) induction of host cell VEGF secretion.

Antioxidants↗

Cloning and expression of Bartonella henselae sucB gene encoding an immunogenic dihydrolipoamide succinyltransferase homologous protein.

Immunoscreening of a ZAP genomic library of Bartonella henselae strain Houston-1 expressed in Escherichia coli resulted in the isolation of a clone containing 3.5 kb BamHI genomic DNA fragment. This 3.5 kb DNA fragment was found to contain a sequence of a gene encoding a protein with significant homology to the dihydrolipoamide succinyltransferase of Brucella melitensis (sucB). Subsequent cloning and DNA sequence analysis revealed that the deduced amino acid sequence from the cloned gene showed 66.5% identity to SucB protein of B. melitensis, and 43.4 and 47.2% identities to those of Coxiella burnetii and E. coli, respectively. The gene was expressed as a His-Nus A-tagged fusion protein. The recombinant SucB protein (rSucB) was shown to be an immunoreactive protein of about 115 kDa by Western blot analysis with sera from B. henselae-immunized mice. Therefore the rSucB may be a candidate antigen for a specific serological diagnosis of B. henselae infection.

Acyltransferases↗

Cat-scratch disease in veterinary-associated populations and in its cat reservoir in Taiwan.

In Taiwan, the first human case of cat-scratch disease (CSD) was diagnosed by a serologic test in 1998. Since then, no studies have been conducted to understand the epidemiology of the infection in Taiwan. Therefore, this study is the first epidemiologic survey of CSD in cats and humans in this country. Using veterinary-associated individuals as the study population, it was identified that 1.7% of them were seropositive for B. henselae, and residence was the only factor associated with seropositivity. Bartonella species were successfully isolated from 25 (19.1%) of the 131 cats tested. Only B. henselae and B. clarridgeiae were obtained from bacteremic cats. Furthermore, 9.2% of 131 cats were dually-infected with genotypes I and II of B. henselae. It is the highest prevalence of co-infection that has ever been reported worldwide. In cats, the seroprevalence was 23.7% by indirect immunofluorescence antibody assay with B. henselae Houston-1 (type I) as the antigen. When 12 bacteremic but seronegative cats were re-tested by IFA slides coated with B. henselae U-4 antigen (type II), 9 cats were identified to be seropositive. Our study further suggested that using only direct PCR of 16S-23S rRNA intergenic region or the combination of the PCR method and indirect immuno-fluorescence test will be useful to diagnose Bartonella-free cats.

Adult↗

Duke criteria-negative endocarditis caused by Bartonella quintana.

Bartonella spp. were recently recognized as causative agents of culture-negative endocarditis. Molecular techniques, such as broad-range PCR, are now available to detect fastidious or slow-growing microorganisms, or those which cannot be cultured. Such microorganisms may be responsible for culture-negative endocarditis. Alcoholism and homelessness are known risk factors for Bartonella quintana endocarditis, even in patients without previous valvular disease. We report a case of B. quintana endocarditis diagnosed by PCR amplification on the excised heart valve, in a young non-alcoholic and immunocompetent patient with few clinical signs of infection who did not fulfill the Duke criteria.

Adult↗

Purification of deformin, an extracellular protein synthesized by Bartonella bacilliformis which causes deformation of erythrocyte membranes.

A factor capable of deforming erythrocyte membranes, found in the culture supernatants of Bartonella bacilliformis, was purified 1840-fold using hydrophobic, ion exchange and gel exclusion chromatography. The final fractions contained a single detectable polypeptide species, referred to as deformin, having a molecular weight of 67000 by SDS-PAGE and a native molecular weight of 130,000 by gel exclusion chromatography or velocity sedimentation in a glycerol gradient. Erythrocytes treated with deformin acquire trenches, indentations, and invaginations which could be reversed by vanadate, dilauroylphosphatidylcholine (DLPC), or by raising the internal Ca2+ concentrations with the inophore A23187. Internal vacuoles also form. Erythrocytes treated with trypsin or neuraminidase are much more sensitive to deformin than untreated erythrocytes; erythrocytes treated with phospholipase D are less sensitive to deformin. This protein may play a role in causing the severe anemia which can result as a consequence of infection by B. bacilliformis.

Bacterial Proteins↗

Bartonella henselae invasion of feline erythrocytes in vitro.

Bartonella henselae, the causative agent of cat scratch disease, establishes long-term bacteremia in cats, in which it attaches to and invades feline erythrocytes (RBC). Feline RBC invasion was assessed in vitro, based on gentamicin selection for intracellular bacteria or by laser confocal microscopy and digital sectioning. Invasion rates ranged from 2 to 20% of the inoculum, corresponding to infection of less than 1% of the RBC. Invasion was a slow process, requiring >8 h before significant numbers of intracellular bacteria were detected. Pretreatment of the bacteria with trypsin, or of the RBC with trypsin or neuraminidase, had no effect, but pronase pretreatment of RBC resulted in a slight increase in invasion frequency. The ability to model B. henselae invasion of feline RBC in vitro should permit identification of bacterial surface components involved in this process and elucidate the significance of RBC invasion to transmission and infection in cats.

Animals↗

Infections in the homeless.

Homeless people in developed countries have specific problems predisposing them to infectious diseases. Respiratory infections and outbreaks of tuberculosis and other aerosol transmitted infections have been reported. Homeless intravenous drug users are at an increased risk of contracting HIV, and hepatitis B and C infections. Skin problems are the main reason the homeless seek medical attention, and these commonly include scabies, pediculosis, tinea infections, and impetigo. Many foot disorders are more prevalent in the homeless including ulcers, cellulitis, erysipelas, and gas gangrene. The louse transmitted bacteria Bartonella quintana has recently been found to cause clinical conditions in the homeless such as urban trench fever, bacillary angiomatosis, endocarditis, and chronic afebrile bacteraemia. Treatment of homeless people is complicated by financial constraints, self-neglect, and lack of adherence. Patients with serious and contagious illnesses should be hospitalised. Physicians should be aware of these specific issues to enhance care.

Adolescent↗

[Cat scratch disease and associated infections].

Cat scratch disease (CSD) was first described in France by Debré et al. in 1950, yet the causative bacterial agent of CSD remained obscure until 1992, when Bartonella (formerly Rochalimaea) henselae was implicated in CSD by serological and microbiologic studies. B. henselae had been linked initially to bacillary angiomatosis (BA), but also bacillary peliosis, relapsing bacteremia and endocarditis. Cats are healthy carriers of B. henselae and B. clarridgeiae, and can be bacteremic for months to years. Cat to cat transmission of the organism involves the cat flea in absence of direct contact transmission. Present knowledge on the etiology, clinical features and epidemiological characteristics of cat scratch disease/bacillary angiomatosis are presented.

Angiomatosis, Bacillary↗

Immunopurified extracellular Bartonella henselae antigen for detecting specific antibodies by enzyme immunoassay.

Protein antigens of Bartonella henselae bacterial sonicate supernatant and concentrated cell-free culture filtrate were examined by SDS-PAGE. The sonicate supernatant gave 38 bands and the culture filtrate at least 21, of which 18 were of bacterial origin. Immunoblotting against 13 monoclonal antibodies obtained from mice infected with live B. henselae showed that 10 of these antibodies reacted with a narrow 225 kDa band and varying smears of bands ranging from 36 to 240 kDa in the sonicate, but only with a single 200 kDa band in the culture filtrate. Testing of pre- and post-infection rabbit sera in immunoblotting against culture filtrate demonstrated that the 200 kDa component gave the most prominent specific reaction with post-infection sera. The 200 kDa antigen was isolated by immunoaffinity chromatography of concentrated culture filtrate, and its molecular size determined by size-exclusion chromatography as > 1000 kDa. The immunopurified antigen was compared with bacterial sonicate as coating antigen in EIA for determining humoral immune responses in rabbits inoculated with live B. henselae. The two antigens gave almost identical results for IgM and IgG responses. The specificity of the immunopurified antigen was tested in EIA against hyperimmune rabbit sera and sera of rabbits inoculated with live B. henselae, B. quintana and Afipia felis. Only the hyperimmune serum against B. henselae and the sera of the rabbits inoculated with live B. henselae reacted with the immunopurified antigen, whereas the B. henselae sonicate cross-reacted with hyperimmune and post-infection sera of rabbits inoculated with B. quintana and A. felis.

Animals↗