Bioluminescence Imaging of Colonization and Clearance Dynamics of Brucella Suis Vaccine Strain S2 in Mice and Guinea Pigs

Wang, Xiwen; Li, Zhiping; Li, Bo; Chi, Hang; Li, Jiakuan; Fan, Hongchao; Yao, Ruizhi; Li, Qianxue; Dong, Xiaolin; Chen, Man; Qu, Han; Wang, Yuanyuan; Gao, Wanli; Wang, Yutian; Sun, Yu; Sun, Rui; Qian, Jun; Xia, Zhang

doi:10.1007/s11307-015-0925-6

Cited by 13 publications

(11 citation statements)

References 21 publications

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“…In the Francisella model (65), 2 × 10 9 radiolabelled bacteria were administrated and their dissemination was only monitored until 20 h post infection. In models using bioluminescent Brucella melitensis (66) and Brucella suis (67), 1 × to 2.5 × 10 7 bacteria were injected. In the spleen of mice infected with 2.5 × 10 7 CFU of B. melitensis , no bioluminescence was detected despite the detection of 4.8 × 10 3 CFU by plating (66), confirming the very poor sensitivity of bioluminescence detection.…”

Section: Discussionmentioning

confidence: 99%

Route of Infection Strongly Impacts the Host-Pathogen Relationship

et al. 2019

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Live attenuated vaccines play a key role in the control of many human and animal pathogens. Their rational development is usually helped by identification of the reservoir of infection, the lymphoid subpopulations associated with protective immunity as well as the virulence genes involved in pathogen persistence. Here, we compared the course of Brucella melitensis infection in C57BL/6 mice infected via intraperitoneal (i.p.), intranasal (i.n.) and intradermal (i.d.) route and demonstrated that the route of infection strongly impacts all of these parameters. Following i.p. and i.n. infection, most infected cells observed in the spleen or lung were F4/80 + myeloid cells. In striking contrast, infected Ly6G + neutrophils and CD140a + fibroblasts were also observed in the skin after i.d. infection. The virB operon encoding for the type IV secretion system is considered essential to deflecting vacuolar trafficking in phagocytic cells and allows Brucella to multiply and persist. Unexpectedly, the Δ virB Brucella strain, which does not persist in the lung after i.n. infection, persists longer in skin tissues than the wild strain after i.d. infection. While the CD4 + T cell-mediated Th1 response is indispensable to controlling the Brucella challenge in the i.p. model, it is dispensable for the control of Brucella in the i.d. and i.n. models. Similarly, B cells are indispensable in the i.p. and i.d. models but dispensable in the i.n. model. γδ + T cells appear able to compensate for the absence of αβ + T cells in the i.d. model but not in the other models. Taken together, our results demonstrate the crucial importance of the route of infection for the host pathogen relationship.

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Section: Discussionmentioning

confidence: 99%

Route of Infection Strongly Impacts the Host-Pathogen Relationship

et al. 2019

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“…Rabbits are medium-sized animals and frequently used in spine research with various advantages compared with other animals [23–26]. Compared with smaller animals (e.g., mice or rats), rabbits maintain considerable morphological and structural similarity to human spine and their body size allows exposing during surgical approaches [10, 14, 27] and yield higher rates than rodents for successful translation of preclinical findings to humans [7, 8].…”

Section: Discussionmentioning

confidence: 99%

Establishment and Initial Testing of a Medium-Sized, Surgically Feasible Animal Model for Brucellar Spondylodiscitis: A Preliminary Study

Cai

Xun

et al. 2019

BioMed Research International

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Brucellar spondylodiscitis, the most prevalent and significant osteoarticular presentation of human Brucellosis, is difficult to diagnose and usually yields irreversible neurologic deficits and spinal deformities. However, no animal models of Brucellar spondylodiscitis exist, allowing for preclinical investigations. The present study investigated whether intraosseous injection of attenuated Brucella melitensis vaccine into rabbits' lumbar vertebrae imitates the radiographic and histopathological characteristics of human Brucellar spondylodiscitis. Radiographic and histopathological analyses at 8 weeks postoperatively revealed radiographic changes within vertebral bodies and intervertebral discs, abscesses formation within the paravertebral soft tissue, and typical prominent inflammation response without caseous necrosis, which were largely comparable to human Brucellar spondylodiscitis. Such a medium-sized, surgically feasible rabbit model provides a promising in vivo setting for further preclinical investigation of Brucellar spondylodiscitis.

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“…The incorporation of luciferase-encoding plasmids into bacteria is a common approach for the development of bioluminescent reporter strains (26). Chromosomally integrated luciferases are often preferred (27), because they are more stable than plasmid-based reporters, although sensitivity is generally lower (17,28).…”

Section: Discussionmentioning

confidence: 99%

A Bioluminescent Francisella tularensis SCHU S4 Strain Enables Noninvasive Tracking of Bacterial Dissemination and the Evaluation of Antibiotics in an Inhalational Mouse Model of Tularemia

Hall

Flick-Smith

Harding

et al. 2016

Antimicrob Agents Chemother

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bBioluminescence imaging (BLI) enables real-time, noninvasive tracking of infection in vivo and longitudinal infection studies. In this study, a bioluminescent Francisella tularensis strain, SCHU S4-lux, was used to develop an inhalational infection model in BALB/c mice. Mice were infected intranasally, and the progression of infection was monitored in real time using BLI. A bioluminescent signal was detectable from 3 days postinfection (3 dpi), initially in the spleen and then in the liver and lymph nodes, before finally becoming systemic. The level of bioluminescent signal correlated with bacterial numbers in vivo, enabling noninvasive quantification of bacterial burdens in tissues. Treatment with levofloxacin (commencing at 4 dpi) significantly reduced the BLI signal. Furthermore, BLI was able to distinguish noninvasively between different levofloxacin treatment regimens and to identify sites of relapse following treatment cessation. These data demonstrate that BLI and SCHU S4-lux are suitable for the study of F. tularensis pathogenesis and the evaluation of therapeutics for tularemia. Francisella tularensis is a Gram-negative intracellular bacterium and is the etiological agent of the disease tularemia. Tularemia has a low infectious dose by the aerosol route (50% infectious dose [ID 50 ], Ͻ10 CFU), causing a disabling illness without rapid treatment, and is considered a potential biothreat agent. The preferred treatments for tularemia are limited to a few antibiotics, including fluoroquinolones (1, 2), tetracycline (3), streptomycin (4, 5), and gentamicin (6, 7). The lack of a licensed vaccine, reported treatment failures, even with preferred antibiotics (8), and a 2% mortality rate despite treatment (5) necessitate the development and evaluation of new therapies.Conventional methods of assessing bacterial growth and dissemination in vivo require the infection of large cohorts of animals and the culling of groups of animals at set time points throughout a study. This strategy not only uses large numbers of animals but is also labor-intensive and subject to tissue sampling bias. Noninvasive imaging techniques, such as bioluminescence imaging (BLI), can report spatial and temporal aspects of infectious diseases in vivo both longitudinally and in real time (9). BLI typically relies on the detection of light produced by luciferase-catalyzed oxidation reactions, which are encoded in the pathogen of interest, by use of a sensitive charge-coupled device (CCD) camera (10). Pivotal experiments by Contag et al. have demonstrated the usefulness of BLI in the noninvasive study of bacterial pathogenesis and the evaluation of antibiotic treatments for Salmonella enterica serovar Typhimurium (11). Subsequently, bioluminescent reporters have been introduced into other bacteria, including Mycobacterium tuberculosis (10, 12), Staphylococcus aureus (13, 14), Burkholderia mallei (15), and Yersinia pestis (16,17). Further, BLI has been used to evaluate vaccines (18), antibiotics (19-21), and supportive therapies (22) for a ran...

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Bioluminescence Imaging of Colonization and Clearance Dynamics of Brucella Suis Vaccine Strain S2 in Mice and Guinea Pigs

Abstract: The plasmid-based lux bioreporter strategy can be used to obtain high resolution in vivo images of B. suis S2 infection in mice and guinea pigs.

Cited by 13 publications

References 21 publications

Route of Infection Strongly Impacts the Host-Pathogen Relationship

Route of Infection Strongly Impacts the Host-Pathogen Relationship

Establishment and Initial Testing of a Medium-Sized, Surgically Feasible Animal Model for Brucellar Spondylodiscitis: A Preliminary Study

A Bioluminescent Francisella tularensis SCHU S4 Strain Enables Noninvasive Tracking of Bacterial Dissemination and the Evaluation of Antibiotics in an Inhalational Mouse Model of Tularemia

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