Dataset Information

Whole Genome Sequencing and Comparative Analysis of Bartonella bacilliformis Strain INS, the Causative Agent of Carrion's Disease.

ABSTRACT: Bartonella bacilliformis is the etiological agent of human bartonellosis, which is highly endemic to Peru. Here, we report the first genome that was sequenced and analyzed from an isolate of B. bacilliformis strain INS, which originally was isolated from the blood of an infected patient with an acute phase of Carrion's disease from Jaén-Cajamarca, Peru.

SUBMITTER: Tarazona D

PROVIDER: S-EPMC3569277 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Whole Genome Sequencing and Comparative Analysis of Bartonella bacilliformis Strain INS, the Causative Agent of Carrion's Disease.

Tarazona D D Padilla C C Cáceres O O Montenegro J D JD Bailón H H Ventura G G Mendoza G G Anaya E E Guio H H

Genome announcements 20130101 1

Bartonella bacilliformis is the etiological agent of human bartonellosis, which is highly endemic to Peru. Here, we report the first genome that was sequenced and analyzed from an isolate of B. bacilliformis strain INS, which originally was isolated from the blood of an infected patient with an acute phase of Carrion's disease from Jaén-Cajamarca, Peru. ...[more]

PMID: 23409255

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Project description:Bartonella bacilliformis is a pathogenic bacterium transmitted to humans presumably by bites of phlebotomine sand flies, infection with which results in a bi-phasic syndrome termed Carrión's disease. After constructing a low-passage GFP-labeled strain of B. bacilliformis, we artificially infected Lutzomyia verrucarum and L. longipalpis populations, and subsequently monitored colonization of sand flies by fluorescence microscopy. Initially, colonization of the two fly species was indistinguishable, with bacteria exhibiting a high degree of motility, yet still confined to the abdominal midgut. After 48 h, B. bacilliformis transitioned from bacillus-shape to a non-motile, small coccoid form and appeared to be digested along with the blood meal in both fly species. Differences in colonization patterns became evident at 72 h when B. bacilliformis was observed at relatively high density outside the peritrophic membrane in the lumen of the midgut in L. verrucarum, but colonization of L. longipalpis was limited to the blood meal within the intra-peritrophic space of the abdominal midgut, and the majority of bacteria were digested along with the blood meal by day 7. The viability of B. bacilliformis in L. longipalpis was assessed by artificially infecting, homogenizing, and plating for determination of colony-forming units in individual flies over a 13-d time course. Bacteria remained viable at relatively high density for approximately seven days, suggesting that L. longipalpis could potentially serve as a vector. The capacity of L. longipalpis to transmit viable B. bacilliformis from infected to uninfected meals was analyzed via interrupted feeds. No viable bacteria were retrieved from uninfected blood meals in these experiments. This study provides significant information toward understanding colonization of sand flies by B. bacilliformis and also demonstrates the utility of L. longipalpis as a user-friendly, live-vector model system for studying this severely neglected tropical disease.

Project description:Analysis of immune responses in Bartonella bacilliformis carriers are needed to understand acquisition of immunity to Carrion's disease and may allow identifying biomarkers associated with bacterial infection and disease phases. Serum samples from 144 healthy subjects from 5 villages in the North of Peru collected in 2014 were analyzed. Four villages had a Carrion's disease outbreak in 2013, and the other is a traditionally endemic area. Thirty cytokines, chemokines and growth factors were determined in sera by fluorescent bead-based quantitative suspension array technology, and analyzed in relation to available data on bacteremia quantified by RT-PCR, and IgM and IgG levels measured by ELISA against B. bacilliformis lysates. The presence of bacteremia was associated with low concentrations of HGF (p = 0.005), IL-15 (p = 0.002), IL-6 (p = 0.05), IP-10 (p = 0.008), MIG (p = 0.03) and MIP-1? (p = 0.03). In multi-marker analysis, the same and further TH1-related and pro-inflammatory biomarkers were inversely associated with infection, whereas angiogenic chemokines and IL-10 were positively associated. Only EGF and eotaxin showed a moderate positive correlation with bacteremia. IgM seropositivity, which reflects a recent acute infection, was associated with lower levels of eotaxin (p = 0.05), IL-6 (p = 0.001), and VEGF (p = 0.03). Only GM-CSF and IL-10 concentrations were positively associated with higher levels of IgM (p = 0.01 and p = 0.007). Additionally, IgG seropositivity and levels were associated with high levels of angiogenic markers VEGF (p = 0.047) and eotaxin (p = 0.006), respectively. Our findings suggest that B. bacilliformis infection causes immunosuppression, led in part by overproduction of IL-10. This immunosuppression probably contributes to the chronicity of asymptomatic infections favoring B. bacilliformis persistence in the host, allowing the subsequent transmission to the vector. In addition, angiogenic markers associated with bacteremia and IgG levels may be related to the induction of endothelial cell proliferation in cutaneous lesions during chronic infections, being possible candidate biomarkers of asymptomatic infections.

Dataset Information

Whole Genome Sequencing and Comparative Analysis of Bartonella bacilliformis Strain INS, the Causative Agent of Carrion's Disease.

Publications

Whole Genome Sequencing and Comparative Analysis of Bartonella bacilliformis Strain INS, the Causative Agent of Carrion's Disease.

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