BAT3 Is Targeted by Legionella pneumophila Translocated Substrates through Co-opted E3 Ubiquitin Ligase Activity
The intracellular pathogen Legionella pneumophila delivers numerous translocated substrates to the host cytosol during infection, and yet the function of the majority of these substrates is unknown. Ensminger and Isberg (p. 3905-3919) demonstrate that two of these bacterial proteins, LegU1 and LegAU13, co-opt host components in order to form functional E3 ubiquitin ligase complexes. A proteomics approach identified the host chaperone protein BAT3 as a target of LegU1-directed polyubiquitination. An unrelated translocated substrate, Lpg2160, also binds BAT3, suggesting that multiple L. pneumophila substrates may modulate the activity of this important host protein during infection.
Chlamydia trachomatis Virulence Factor Identified by In Vivo Selection and Comparative Genomic Sequencing
Chlamydia trachomatis is a major cause of sexually transmitted infection. Advances in understanding C. trachomatis pathogenesis and immunity to infection have been hampered by the lack of a suitable murine animal model. By using in vivo selection and comparative genomics of strains differing in pathogenicity, Sturdevant et al. (p. 3660-3668) demonstrate that frameshift mutations in a single gene are sufficient to increase the virulence of C. trachomatis for the female murine genital tract. This work provides new insights about C. trachomatis pathogenesis that are important to future murine modeling studies and offers novel approaches for understanding human infection and disease.
Natural Selection In Vivo Identifies Essential Kinase Residues for Phosphorylation of Pasteurella multocida Lipopolysaccharide
Pasteurella multocida is very unusual in producing two full-length lipopolysaccharide (LPS) glycoforms (A and B) during in vivo growth in chickens. A mutant that expresses truncated glycoform A and full-length glycoform B is avirulent. However, Harper et al. (p. 3669-3677) show that chickens inoculated with high doses of this mutant become infected with P. multocida that no longer expresses any truncated LPS. These in vivo-derived mutants all harbor compensatory suppressor mutations within KdkA, a kinase essential for the assembly of glycoform A LPS. Analysis of these in vivo-derived LPS mutants allowed the identification of four amino acid residues essential for KdkA function.
Different Histoplasma Cell Types Elicit Distinct Host Responses
Fungal pathogens are notorious for undergoing cell shape changes as they colonize mammalian hosts. During natural infections with Histoplasma capsulatum, environmental spores (conidia) are inhaled into the lungs of the host, where they germinate to give rise to budding yeast cells that colonize macrophages and cause disease. Inglis et al. (p. 3871-3882) demonstrate that murine macrophages induce type I interferon-responsive genes during infection with Histoplasma conidia but not Histoplasmayeast cells. These findings suggest that distinct fungal cell types from the same organism can induce differential host responses that could influence the progression of disease.
Global Gene Expression Profiling of Yersinia pestis Replicating inside Macrophages
Yersinia pestis is a facultative intracellular bacterial pathogen. The ability to survive inside macrophage phagosomes is thought to play an important role during early stages of plague pathogenesis. Through transcriptome analysis, Fukuto et al. (p. 3700-3715) uncover Y. pestis genes important for various aspects of intracellular life, including those in known metabolic and stress response pathways as well as previously uncharacterized factors. Deletion of a novel operon highly induced in the phagosome resulted in altered intracellular replication rate and bacterial morphology, as well as reduced secretion of virulence factors, suggesting the possible role of this operon in allowing Y. pestis to cope with intracellular stresses by modifying cell envelope characteristics.
- Copyright © 2010 American Society for Microbiology
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- BAT3 Is Targeted by Legionella pneumophila Translocated Substrates through Co-opted E3 Ubiquitin Ligase Activity
- Chlamydia trachomatis Virulence Factor Identified by In Vivo Selection and Comparative Genomic Sequencing
- Natural Selection In Vivo Identifies Essential Kinase Residues for Phosphorylation of Pasteurella multocida Lipopolysaccharide
- Different Histoplasma Cell Types Elicit Distinct Host Responses
- Global Gene Expression Profiling of Yersinia pestis Replicating inside Macrophages
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