Decrease In Bacterial Burden Research Articles

Staphylococcal Enterotoxin B–Specific Monoclonal Antibody 20B1 Successfully Treats Diverse Staphylococcus aureus Infections

Methicillin-resistant Staphylococcus aureus (MRSA) has become a major health threat in the United States. Staphylococcal enterotoxin B (SEB) is a potent superantigen that contributes to its virulence. High mortality and frequent failure of therapy despite available antibiotics have stimulated research efforts to develop adjunctive therapies. Treatment benefits of SEB-specific monoclonal antibody (mAb) 20B1 were investigated in mice in sepsis, superficial skin, and deep-tissue infection models. Mice challenged with a SEB-producing MRSA strain developed fatal sepsis, extensive tissue skin infection, and abscess-forming deep-seeded thigh muscle infection. Animals preimmunized against SEB or treated passively with mAb 20B1 exhibited enhanced survival in the sepsis model, whereas decrease of bacterial burden was observed in the superficial skin and deep-tissue models. mAb 20B1 bound to SEB in the infected tissue and decreased abscess formation and proinflammatory cytokine levels, lymphocyte proliferation, and neutrophil recruitment. mAb 20B1, an SEB-neutralizing mAb, is effective against MRSA infection. mAb 20B1 protects against lethal sepsis and reduces skin tissue invasion and deep-abscess formation. The mAb penetrates well into the abscess and binds to SEB. It affects the outcome of S. aureus infection by modulating the host's proinflammatory immune response.

Comparative study of IFNγ and antibody tests for feline tuberculosis

This study describes the comparison of the cell-based interferon-gamma (IFNγ) test with serological rapid antibody tests (STAT-PAK and DPP VetTB) for the ante mortem testing of tuberculosis in domestic cats. The antibody specificities of rapid antibody test-positive cats were further discerned using multi-antigen print immunoassay. A total of 62 cats with culture-confirmed Mycobacterium bovis, Mycobacterium microti, Mycobacterium avium and Mycobacterium malmoense, as well as negative controls and dangerous-contact cats were tested. Tests were also applied longitudinally to one further cat undergoing TB chemotherapy for suspected M. bovis infection. Our data from this small study show excellent test specificity (100% for all tests) and encouraging levels of test sensitivity for M. bovis and TB Complex infections (IFNγ 70–100% depending upon test interpretation criteria; rapid tests both 90% for M. bovis infection and up to 46.2% for M. microti infection). The differential diagnosis of very pathogenic TB Complex ( M. bovis, Mycobacterium tuberculosis), as opposed to less-pathogenic TB Complex ( M. microti) was possible where positive responses to the protein cocktail ESAT6/CFP10 were observed (80% of M. bovis-infected cats in this study showed positive IFNγ responses to ESAT6/CFP10, while 20% had antibody responses to ESAT6/CFP10 using MAPIA). Finally, preliminary data from a longitudinal study of one M. bovis-exposed cat with a positive IFNγ test pre-treatment suggest that a decrease in bacterial burden may be reflected in the IFNγ response, and thus the IFNγ test may provide a monitor for TB chemotherapy.

Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography

Background S. aureus acquires heme-iron using the iron regulated surface determinant (Isd) system and the heme transport system (Hts) with both systems showing critical importance in systemic models of infection. The contribution of heme-iron acquisition to staphylococcal pneumonia has not yet been elucidated. In addition, the use of computed tomography (CT) for the evaluation of staphylococcal pneumonia and its correlation to pathologic examination of infected lung tissue has not been performed to date. We have applied CT-based imaging to a murine model of staphylococcal pneumonia to determine the virulence contribution of heme-iron acquisition through the Hts and Isd systems.Methodology/Principal FindingsMice were intranasally inoculated with ∼1.0×108 colony forming units (CFU) of S. aureus. Lungs from mice infected with wild type S. aureus or strains deficient in isdB and isdH (ΔisdBH) or htsA and isdE (ΔhtsAΔisdE) were harvested at 24 hours. Histology, radiographic appearance by computed tomography (CT), percent mortality and bacterial burden were evaluated. Infection with S. aureus ΔisdBH and ΔhtsAΔisdE did not result in a statistically significant difference in mortality or bacterial burden as compared to controls. CT imaging of infected mice also did not reveal an appreciable difference between the various strains when compared to wild type, but did correlate with pathologic findings of pneumonia. However, a systemic model of infection using the ΔhtsAΔisdE strain revealed a statistically significant decrease in bacterial burden in the lung, heart and kidneys.Conclusions/SignificanceThe development of staphylococcal pneumonia in this murine model is not dependent on hemoglobin binding or heme-iron uptake into S. aureus. However, this model does reveal that heme-iron acquisition contributes to the pathogenesis of systemic staphylococcal infections. In addition, CT imaging of murine lungs is an attractive adjunct to histologic analysis for the confirmation and staging of pneumonia.

B7.1 and B7.2 are crucial for primary response to Mycobacterium tuberculosis infection but redundant for the induction of memory response (45.24)

Abstract Costimulation plays a crucial role in priming of naïve T cell to an effector cell type. In a recent study, we have shown that lack of B7.1 and B7.2 (DKO) causes the host to generate a dampened Th1 effector response, disabling it to contain the bacterial burden during chronic phase of infection. Since the development of T cell memory is connected to the effector T cell response, we sought to investigate how a defective primary effector response will affect the induction of the memory. Memory mice were generated by treating infected wildtype (WT) and DKO mice with antibiotics and resting them after the treatment. These memory mice along with age matched naïve controls were then challenged with low dose infection with M. tuberculosis. A significant decrease in bacterial burden was seen in both WT and DKO memory mice at 4 and 6 weeks post infection when compared to naive WT and DKO mice respectively. This decreased bacterial burden was accompanied with a faster Th1 effector response in both WT and DKO memory lungs as indicated by increased number of IFNγ producing cells in the lungs. These results indicate that despite its inability to generate a defective primary response the DKO host is able to mount a memory response against M.tuberculosis infection. Further studies are in progress to study the mechanism of memory induction in the absence of a successful primary response in the DKO mice. This study was supported by NIH Grant AI 49778, Potts Memorial Foundation Award and UMDNJ Foundation Award.