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The differential interaction of Brucella and ochrobactrum with innate immunity reveals traits related to the evolution of stealthy pathogens.

Barquero-Calvo E, Conde-Alvarez R, Chacón-Díaz C, Quesada-Lobo L, Martirosyan A, Guzmán-Verri C, Iriarte M, Mancek-Keber M, Jerala R, Gorvel JP, Moriyón I, Moreno E, Chaves-Olarte E - PLoS ONE (2009)

Bottom Line: During evolution, innate immunity has been tuned to recognize pathogen-associated molecular patterns.The results suggest that Brucellaceae ancestors carried molecules not readily recognized by innate immunity, so that non-drastic variations led to the emergence of stealthy intracellular parasites.They also suggest that some critical envelope properties, like selective permeability, are profoundly altered upon modification of pathogen-associated molecular patterns, and that this represents a further adaptation to the host.

View Article: PubMed Central - PubMed

Affiliation: Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.

ABSTRACT

Background: During evolution, innate immunity has been tuned to recognize pathogen-associated molecular patterns. However, some alpha-Proteobacteria are stealthy intracellular pathogens not readily detected by this system. Brucella members follow this strategy and are highly virulent, but other Brucellaceae like Ochrobactrum are rhizosphere inhabitants and only opportunistic pathogens. To gain insight into the emergence of the stealthy strategy, we compared these two phylogenetically close but biologically divergent bacteria.

Methodology/principal findings: In contrast to Brucella abortus, Ochrobactrum anthropi did not replicate within professional and non-professional phagocytes and, whereas neutrophils had a limited action on B. abortus, they were essential to control O. anthropi infections. O. anthropi triggered proinflammatory responses markedly lower than Salmonella enterica but higher than B. abortus. In macrophages and dendritic cells, the corresponding lipopolysaccharides reproduced these grades of activation, and binding of O. anthropi lipopolysaccharide to the TLR4 co-receptor MD-2 and NF-kappaB induction laid between those of B. abortus and enteric bacteria lipopolysaccharides. These differences correlate with reported variations in lipopolysaccharide core sugars, sensitivity to bactericidal peptides and outer membrane permeability.

Conclusions/significance: The results suggest that Brucellaceae ancestors carried molecules not readily recognized by innate immunity, so that non-drastic variations led to the emergence of stealthy intracellular parasites. They also suggest that some critical envelope properties, like selective permeability, are profoundly altered upon modification of pathogen-associated molecular patterns, and that this represents a further adaptation to the host. It is proposed that this adaptive trend is relevant in other intracellular alpha-Proteobacteria like Bartonella, Rickettsia, Anaplasma, Ehrlichia and Wolbachia.

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O. anthropi infection induces an intermediate blood leukocyte response.Groups of 6 mice were inoculated intraperitoneally with106 CFU/ml of the indicated bacteria, bleed at different times and leukocytes counted in blood. (A) Total leukocytes number of mice infected with the indicated bacteria. (B) Relative blood leukocyte number of mice infected with B. abortus. (C) Relative blood leukocyte number of mice infected with S. enterica. (D) Relative blood leukocyte number of mice infected with O. anthropi. Values of O. anthropi in “A” were significantly different at p<0.01 (*) and p<0.001 (**) with respect to B. abortus. In “B, C and D” the standard error was less that 5% at all points.
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pone-0005893-g003: O. anthropi infection induces an intermediate blood leukocyte response.Groups of 6 mice were inoculated intraperitoneally with106 CFU/ml of the indicated bacteria, bleed at different times and leukocytes counted in blood. (A) Total leukocytes number of mice infected with the indicated bacteria. (B) Relative blood leukocyte number of mice infected with B. abortus. (C) Relative blood leukocyte number of mice infected with S. enterica. (D) Relative blood leukocyte number of mice infected with O. anthropi. Values of O. anthropi in “A” were significantly different at p<0.01 (*) and p<0.001 (**) with respect to B. abortus. In “B, C and D” the standard error was less that 5% at all points.

Mentions: We also monitored the changes in blood after peritoneal inoculation in comparison with B. abortus and S. enterica. Although there was a quick initial decrease in the circulating leukocytes in the three cases, numbers remained low in mice inoculated with S. enterica. In contrast, there was a rapid return to basal levels in B. abortus inoculated mice and an intermediate phenotype, slightly closer to that of B. abortus, obtained with O. anthropi (Fig. 3A). The evaluation of the blood leukocyte populations showed a moderate change in the proportion of neutrophils in mice inoculated with B. abortus (Fig. 3B) and a rapid increase of the same cells in mice inoculated with S. enterica (Fig. 3C). Again, O. anthropi triggered an intermediate response (Fig. 3D).


The differential interaction of Brucella and ochrobactrum with innate immunity reveals traits related to the evolution of stealthy pathogens.

Barquero-Calvo E, Conde-Alvarez R, Chacón-Díaz C, Quesada-Lobo L, Martirosyan A, Guzmán-Verri C, Iriarte M, Mancek-Keber M, Jerala R, Gorvel JP, Moriyón I, Moreno E, Chaves-Olarte E - PLoS ONE (2009)

O. anthropi infection induces an intermediate blood leukocyte response.Groups of 6 mice were inoculated intraperitoneally with106 CFU/ml of the indicated bacteria, bleed at different times and leukocytes counted in blood. (A) Total leukocytes number of mice infected with the indicated bacteria. (B) Relative blood leukocyte number of mice infected with B. abortus. (C) Relative blood leukocyte number of mice infected with S. enterica. (D) Relative blood leukocyte number of mice infected with O. anthropi. Values of O. anthropi in “A” were significantly different at p<0.01 (*) and p<0.001 (**) with respect to B. abortus. In “B, C and D” the standard error was less that 5% at all points.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2691993&req=5

pone-0005893-g003: O. anthropi infection induces an intermediate blood leukocyte response.Groups of 6 mice were inoculated intraperitoneally with106 CFU/ml of the indicated bacteria, bleed at different times and leukocytes counted in blood. (A) Total leukocytes number of mice infected with the indicated bacteria. (B) Relative blood leukocyte number of mice infected with B. abortus. (C) Relative blood leukocyte number of mice infected with S. enterica. (D) Relative blood leukocyte number of mice infected with O. anthropi. Values of O. anthropi in “A” were significantly different at p<0.01 (*) and p<0.001 (**) with respect to B. abortus. In “B, C and D” the standard error was less that 5% at all points.
Mentions: We also monitored the changes in blood after peritoneal inoculation in comparison with B. abortus and S. enterica. Although there was a quick initial decrease in the circulating leukocytes in the three cases, numbers remained low in mice inoculated with S. enterica. In contrast, there was a rapid return to basal levels in B. abortus inoculated mice and an intermediate phenotype, slightly closer to that of B. abortus, obtained with O. anthropi (Fig. 3A). The evaluation of the blood leukocyte populations showed a moderate change in the proportion of neutrophils in mice inoculated with B. abortus (Fig. 3B) and a rapid increase of the same cells in mice inoculated with S. enterica (Fig. 3C). Again, O. anthropi triggered an intermediate response (Fig. 3D).

Bottom Line: During evolution, innate immunity has been tuned to recognize pathogen-associated molecular patterns.The results suggest that Brucellaceae ancestors carried molecules not readily recognized by innate immunity, so that non-drastic variations led to the emergence of stealthy intracellular parasites.They also suggest that some critical envelope properties, like selective permeability, are profoundly altered upon modification of pathogen-associated molecular patterns, and that this represents a further adaptation to the host.

View Article: PubMed Central - PubMed

Affiliation: Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.

ABSTRACT

Background: During evolution, innate immunity has been tuned to recognize pathogen-associated molecular patterns. However, some alpha-Proteobacteria are stealthy intracellular pathogens not readily detected by this system. Brucella members follow this strategy and are highly virulent, but other Brucellaceae like Ochrobactrum are rhizosphere inhabitants and only opportunistic pathogens. To gain insight into the emergence of the stealthy strategy, we compared these two phylogenetically close but biologically divergent bacteria.

Methodology/principal findings: In contrast to Brucella abortus, Ochrobactrum anthropi did not replicate within professional and non-professional phagocytes and, whereas neutrophils had a limited action on B. abortus, they were essential to control O. anthropi infections. O. anthropi triggered proinflammatory responses markedly lower than Salmonella enterica but higher than B. abortus. In macrophages and dendritic cells, the corresponding lipopolysaccharides reproduced these grades of activation, and binding of O. anthropi lipopolysaccharide to the TLR4 co-receptor MD-2 and NF-kappaB induction laid between those of B. abortus and enteric bacteria lipopolysaccharides. These differences correlate with reported variations in lipopolysaccharide core sugars, sensitivity to bactericidal peptides and outer membrane permeability.

Conclusions/significance: The results suggest that Brucellaceae ancestors carried molecules not readily recognized by innate immunity, so that non-drastic variations led to the emergence of stealthy intracellular parasites. They also suggest that some critical envelope properties, like selective permeability, are profoundly altered upon modification of pathogen-associated molecular patterns, and that this represents a further adaptation to the host. It is proposed that this adaptive trend is relevant in other intracellular alpha-Proteobacteria like Bartonella, Rickettsia, Anaplasma, Ehrlichia and Wolbachia.

Show MeSH
Related in: MedlinePlus