Abstract
Pathogenic intracellular bacteria can respond to antimicrobial mechanisms of the host cell through transient activation of stress-responsive genes by alternative sigma (σ) factors of the RNA polymerase. We evaluated the contribution of the extracytoplasmic function sigma factor σE for Corynebacterium pseudotuberculosis resistance to stress conditions resembling those found intracellularly during infection. A sigE-null mutant strain (ΔsigE) of this bacterium was more susceptible in vitro to acidic pH, cell surface stressors, and biologically relevant concentrations of nitric oxide (NO). The same mutant strain was unable to persist in C57BL/6 mice but remained infective in mice lacking inducible nitric oxide synthase (iNOS), confirming the significance of σE for resistance to nitric oxide/peroxide stress in vivo. High-throughput proteomic analysis identified NO-responsive extracellular proteins of C. pseudotuberculosis and demonstrated the participation of σE in composition of this bacterium’s exoproteome.
Highlights
Corynebacterium pseudotuberculosis, a pathogenic bacterium belonging to the so-called CMN-group of Actinobacteria, is the etiological agent of various disease manifestations in different hosts, including humans (Dorella et al, 2006; Trost et al, 2010)
PSEUDOTUBERCULOSIS IS MORE SENSITIVE TO CELL SURFACE STRESSORS, ACIDIC PH, AND IN VITRO-GENERATED NITRIC OXIDE In order to evaluate the role played by the extracytoplasmic function (ECF) sigma factor σE in C. pseudotuberculosis resistance to stress conditions faced during intracellular infection, a sigE-null mutant strain of this bacterium (ΔsigE) was generated by homologous recombination in the parental strain 1002
The mutant strain was more sensitive to an acidic pH that resembles that found within an activated macrophage, and to cell surface stressors, namely SDS and lysozyme treatments (Figure 1), corroborating previous studies on the role of σE in resistance to environmental-stresses in other corynebacteria and mycobacteria (Manganelli et al, 2001; Park et al, 2008)
Summary
Corynebacterium pseudotuberculosis, a pathogenic bacterium belonging to the so-called CMN-group of Actinobacteria, is the etiological agent of various disease manifestations in different hosts, including humans (Dorella et al, 2006; Trost et al, 2010). C. pseudotuberculosis survives phagocytosis to remain as an intracellular parasite within phagocytic cells (Stefanska et al, 2010). This is achieved by overcoming the innate antimicrobial defense mechanisms of the host cells. These cells create a harsh environment inside the phagolysosome by generating reactive oxygen and nitrogen intermediates, via phagocyte oxidase (Phox) and inducible nitric oxide synthase (iNOS), respectively (Nathan and Shiloh, 2000)
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