Abstract
Bovine tuberculosis (bTB) is a highly transmissible infection and remains of great concern as a zoonosis. The worldwide incidence of bTB is in rise, creating potential reservoir and increased infection risk for humans and animals. In attempts to identify novel surface antigens of Mycobacterium bovis as a proof-of-concept for potential inducers of protective immunity, we investigated surface proteome of M. bovis BCG strain that was cultured under the granuloma-like condition. We also demonstrated that the pathogen exposed to the biologically relevant environment has greater binding and invasion abilities to host cells than those of bacteria incubated under regular laboratory conditions. A total of 957 surface-exposed proteins were identified for BCG cultured under laboratory condition, whereas 1,097 proteins were expressed under the granuloma-like condition. The overexpression of Mb1524, Mb01_03198, Mb1595_p3681 (PhoU1 same as phoY1_1), and Mb1595_p0530 (HbhA) surface proteins in Mycobacterium smegmatis leads to increased binding and invasion to mucosal cells. We also examined the immunogenicity of purified recombinant proteins and tested M. smegmatis overexpressing these surface antigens for the induction of protective immunity in mice. Significantly high levels of specific IgA and IgG antibodies were observed in recombinant protein immunized groups by both inhalation and intraperitoneal (IP) routes, but only IP delivery induced high total IgA and IgG levels. We did not detect major differences in antibody levels in the M. smegmatis group that overexpressed surface antigens. In addition, the bacterial load was significantly reduced in the lungs of mice immunized with the combination of inhaled recombinant proteins. Our findings suggest that the activation of the mucosal immunity can lead to increased ability to confer protection upon M. bovis BCG infection.
Highlights
Bovine tuberculosis is a significant zoonotic threat that is associated with both animal losses with substantial economic consequences and a high risk for human infection.e global impact of bTB is estimated at US $3 billion per year [1]
M. bovis BCG exposed to the environment mimicking the granuloma-like condition for 24 hrs is able to bind to A549 cells with significantly greater efficiency than bacteria cultured in regular laboratory conditions (Figure 1(a))
M. bovis BCG exposed to granuloma-like condition attaches with significantly higher efficacy to THP-1 macrophages when compared to the binding percentage of bacteria cultured in regular laboratory conditions at both 30 min and 1 h time points (Figure 1(b))
Summary
Bovine tuberculosis (bTB) is a significant zoonotic threat that is associated with both animal losses with substantial economic consequences and a high risk for human infection.e global impact of bTB is estimated at US $3 billion per year [1]. Bovine tuberculosis (bTB) is a significant zoonotic threat that is associated with both animal losses with substantial economic consequences and a high risk for human infection. A number of measures have been adopted to control the infection, the incidence of the disease is on the rise [2]. E diagnoses of bovine tuberculosis in many countries still depend on indirect methods, such as using PPD, and in the majority of the cases, chemotherapy is not a practical alternative to treat infected animals. Respiratory and gastrointestinal tracts are the main routes for acquiring Mycobacterium bovis. Vaccination, remains the most effective and feasible approach to control the infection. Some countries still utilize the human M. tuberculosis vaccine (Mycobacterium bovis BCG) to immunize cattle, current bTB epidemiologic studies indicate that it does not protect animals from infection.
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