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Neurotropic threat characterization of Burkholderia pseudomallei strains.

Morris J, Fane A, Rush C, Govan B, Mayo M, Currie BJ, Ketheesan N - Emerging Infect. Dis. (2015)

Bottom Line: Rather, a distinct subset of B. pseudomallei strains appear to have heightened pathogenic potential for rapid dissemination to multiple tissues, including the central nervous system, irrespective of the infection route.This finding has valuable public health ramifications for initiating appropriate and timely therapy after exposure to systemically invasive B. pseudomallei strains.Increasing understanding of B. pseudomallei pathology and its influencing factors will further reduce illness and death from this disease.

View Article: PubMed Central - PubMed

ABSTRACT
The death rate for neurologic melioidosis is high. Whether certain Burkholderia pseudomallei strains are more likely than other strains to cause central nervous system infection and whether route of infection influences the neurotropic threat remain unclear. Therefore, we compared the virulence and dissemination of Australian clinical isolates collected during October 1989-October 2012 from patients with neurologic and nonneurologic melioidosis after intranasal and subcutaneous infection of mice in an experimental model. We did not observe neurotropism as a unique characteristic of isolates from patients with neurologic melioidosis. Rather, a distinct subset of B. pseudomallei strains appear to have heightened pathogenic potential for rapid dissemination to multiple tissues, including the central nervous system, irrespective of the infection route. This finding has valuable public health ramifications for initiating appropriate and timely therapy after exposure to systemically invasive B. pseudomallei strains. Increasing understanding of B. pseudomallei pathology and its influencing factors will further reduce illness and death from this disease.

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Comparison of Burkholderia pseudomallei loads in organs of BALB/c mice at days 1 (A, B), 3 (C, D) and 7 (E, F) after intranasal (white bars) and subcutaneous (black bars) infection with the neurologic isolates MSHR435 (5 × 102 CFU; panels A, C, E) and MSHR1153 (4.5 × 102 CFU; panels B, D, F) , Northern Territory, Australia, October 1989–October 2012. Bacterial loads were assessed in NALT, cLN, iLN, blood, lung, brain, spleen, liver, and SAT at the indicated dpi. Five mice were assessed at each time point. Data are expressed as mean l;og10 CFU per tissue ± SEM. cLN, cervical lymph nodes; dpi, days postinfection; iLN, inguinal lymph nodes; NALT, nasal-associated lymphoid tissue; SAT, subcutaneous adipose tissue. Error bars indicate standard error of the mean.
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Figure 2: Comparison of Burkholderia pseudomallei loads in organs of BALB/c mice at days 1 (A, B), 3 (C, D) and 7 (E, F) after intranasal (white bars) and subcutaneous (black bars) infection with the neurologic isolates MSHR435 (5 × 102 CFU; panels A, C, E) and MSHR1153 (4.5 × 102 CFU; panels B, D, F) , Northern Territory, Australia, October 1989–October 2012. Bacterial loads were assessed in NALT, cLN, iLN, blood, lung, brain, spleen, liver, and SAT at the indicated dpi. Five mice were assessed at each time point. Data are expressed as mean l;og10 CFU per tissue ± SEM. cLN, cervical lymph nodes; dpi, days postinfection; iLN, inguinal lymph nodes; NALT, nasal-associated lymphoid tissue; SAT, subcutaneous adipose tissue. Error bars indicate standard error of the mean.

Mentions: Regardless of the route of infection, dissemination occurred rapidly; bacteria were detected not only at sites of infection but also in draining lymph nodes and spleen by 1 dpi (Figure 2, panels A and B). Bacterial loads continued to increase significantly from 3 dpi (Figure 2, panels C, D) through 7 dpi (Figure 2, panels E, F), with comparable levels in spleen, liver, and lung after intranasal or subcutaneous infection for MSHR435 and MSHR1153. Bacterial loads in the brain of mice infected with MSHR435 and MSHR1153 were low or undetectable within the first week after infection, consistent with the tendency for neurologic signs to develop after 8 dpi. The levels of bacteria recovered from brain after intranasal or subcutaneous infection with MSHR435 or MSHR1153 did not differ between 3 dpi and 7 dpi.


Neurotropic threat characterization of Burkholderia pseudomallei strains.

Morris J, Fane A, Rush C, Govan B, Mayo M, Currie BJ, Ketheesan N - Emerging Infect. Dis. (2015)

Comparison of Burkholderia pseudomallei loads in organs of BALB/c mice at days 1 (A, B), 3 (C, D) and 7 (E, F) after intranasal (white bars) and subcutaneous (black bars) infection with the neurologic isolates MSHR435 (5 × 102 CFU; panels A, C, E) and MSHR1153 (4.5 × 102 CFU; panels B, D, F) , Northern Territory, Australia, October 1989–October 2012. Bacterial loads were assessed in NALT, cLN, iLN, blood, lung, brain, spleen, liver, and SAT at the indicated dpi. Five mice were assessed at each time point. Data are expressed as mean l;og10 CFU per tissue ± SEM. cLN, cervical lymph nodes; dpi, days postinfection; iLN, inguinal lymph nodes; NALT, nasal-associated lymphoid tissue; SAT, subcutaneous adipose tissue. Error bars indicate standard error of the mean.
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Related In: Results  -  Collection

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Figure 2: Comparison of Burkholderia pseudomallei loads in organs of BALB/c mice at days 1 (A, B), 3 (C, D) and 7 (E, F) after intranasal (white bars) and subcutaneous (black bars) infection with the neurologic isolates MSHR435 (5 × 102 CFU; panels A, C, E) and MSHR1153 (4.5 × 102 CFU; panels B, D, F) , Northern Territory, Australia, October 1989–October 2012. Bacterial loads were assessed in NALT, cLN, iLN, blood, lung, brain, spleen, liver, and SAT at the indicated dpi. Five mice were assessed at each time point. Data are expressed as mean l;og10 CFU per tissue ± SEM. cLN, cervical lymph nodes; dpi, days postinfection; iLN, inguinal lymph nodes; NALT, nasal-associated lymphoid tissue; SAT, subcutaneous adipose tissue. Error bars indicate standard error of the mean.
Mentions: Regardless of the route of infection, dissemination occurred rapidly; bacteria were detected not only at sites of infection but also in draining lymph nodes and spleen by 1 dpi (Figure 2, panels A and B). Bacterial loads continued to increase significantly from 3 dpi (Figure 2, panels C, D) through 7 dpi (Figure 2, panels E, F), with comparable levels in spleen, liver, and lung after intranasal or subcutaneous infection for MSHR435 and MSHR1153. Bacterial loads in the brain of mice infected with MSHR435 and MSHR1153 were low or undetectable within the first week after infection, consistent with the tendency for neurologic signs to develop after 8 dpi. The levels of bacteria recovered from brain after intranasal or subcutaneous infection with MSHR435 or MSHR1153 did not differ between 3 dpi and 7 dpi.

Bottom Line: Rather, a distinct subset of B. pseudomallei strains appear to have heightened pathogenic potential for rapid dissemination to multiple tissues, including the central nervous system, irrespective of the infection route.This finding has valuable public health ramifications for initiating appropriate and timely therapy after exposure to systemically invasive B. pseudomallei strains.Increasing understanding of B. pseudomallei pathology and its influencing factors will further reduce illness and death from this disease.

View Article: PubMed Central - PubMed

ABSTRACT
The death rate for neurologic melioidosis is high. Whether certain Burkholderia pseudomallei strains are more likely than other strains to cause central nervous system infection and whether route of infection influences the neurotropic threat remain unclear. Therefore, we compared the virulence and dissemination of Australian clinical isolates collected during October 1989-October 2012 from patients with neurologic and nonneurologic melioidosis after intranasal and subcutaneous infection of mice in an experimental model. We did not observe neurotropism as a unique characteristic of isolates from patients with neurologic melioidosis. Rather, a distinct subset of B. pseudomallei strains appear to have heightened pathogenic potential for rapid dissemination to multiple tissues, including the central nervous system, irrespective of the infection route. This finding has valuable public health ramifications for initiating appropriate and timely therapy after exposure to systemically invasive B. pseudomallei strains. Increasing understanding of B. pseudomallei pathology and its influencing factors will further reduce illness and death from this disease.

Show MeSH
Related in: MedlinePlus