[Virulence determinant of Chromobacterium violaceum].

Abstract

Chromobacterium violaceum is a Gram-negative bacterium that infects humans and animals with fatal sepsis. The infection with C. violaceum is rare in case of those who are healthy, but once established, C. violaceum causes sever disease accompanied by abscess formation in the lungs, liver and spleen. Furthermore, C. violaceum is resistant to a broad range of antibiotics, which in some cases renders the antimicrobial therapy for this infection difficult. Thus, the infection with C. violaceum displays high mortality rates unless initial proper antimicrobial therapy. In contrast, the infection mechanism had completely remained unknown. To this end, we have tried to identify virulence factors-associated with C. violaceum infection. Two distinct type III secretion systems (TTSSs) were thought to be one of the most important virulence factors, which are encoded by Chromobacterium pathogenicity island 1/1a and 2 (Cpi-1/-1a and -2) respectively. Our results have shown that Cpi-1/-1a-encoded TTSS, but not Cpi-2, is indispensable for the virulence in a mouse infection model. C. violaceum caused fulminant hepatitis in a Cpi-1/-1a-encoded TTSS-dependent manner. We next have identified 16 novel effectors secreted from Cpi-1/-1a-encoded TTS machinery. From these effectors, we found that CopE (Chromobacterium outer protein E) has similarities to a guanine nucleotide exchange factor (GEF) for Rho GTPases. CopE acts as GEF for Rac1 and Cdc42, leading to induction of actin cytoskeletal rearrangement. Interestingly, C. violaceum invades cultured human epithelial cells in a CopE-dependent manner. Finally, an inactivation of CopE by disruption of copE gene or amino acid point mutation leading to loss of GEF activity attenuates significantly the mouse virulence of C. violaceum. These results suggest that Cpi-1/-1a-encoded TTSS is a major virulence determinant for C. violaceum infection, and that CopE contributes to the virulence in part of this pathogen.

• Authors: Tsuyoshi Miki
• Journal: Nihon saikingaku zasshi. Japanese journal of bacteriology (Nihon Saikingaku Zasshi) Vol. 69 Issue 4 Pg. 577-88 ( 2014) ISSN: 1882-4110 [Electronic] Japan
• PMID: 25447983 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• cdc42 GTP-Binding Protein
• rac1 GTP-Binding Protein

Topics

• Animals
• Chromobacterium (genetics, pathogenicity)
• Disease Models, Animal
• Genomic Islands (genetics, physiology)
• Gram-Negative Bacterial Infections (microbiology)
• Humans
• Mice
• Multigene Family (genetics)
• Virulence
• cdc42 GTP-Binding Protein (metabolism)
• rac1 GTP-Binding Protein (metabolism)