Virulence plasmid of Aeromonas hydrophila induces macrophage apoptosis and helps in developing systemic infection in mice

• Published in: Microbial pathogenesis Vol. 46; no. 2; pp. 98 - 107
• Main Authors: Majumdar, Tanmay, Chattopadhyay, Pritam, Saha, Dhira Rani, Sau, Subrato, Mazumder, Shibnath
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier India Pvt Ltd 01-02-2009; Elsevier
• Subjects: Aeromonas hydrophila; Aeromonas hydrophila - genetics; Aeromonas hydrophila - growth & development; Aeromonas hydrophila - pathogenicity; Animals; Apoptosis; Bacteriology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gram-Negative Bacterial Infections - microbiology; Infection; Macrophage; Macrophages - microbiology; Macrophages - physiology; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Plasmid; Plasmids; Reactive Oxygen Species - metabolism; Virulence - genetics; Plasmid; Infection; Aeromonas hydrophila; Macrophage; Apoptosis; Microbiology; Virulence; Rodentia; Vertebrata; Mammalia; Mouse; Cell death; Bacteria; Vibrionaceae
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2008.11.002

Pathogenic
Aeromonas hydrophila Strain AO1 bears a 21
kb plasmid encoding several virulence determinants. Infection studies revealed that this isolate induced cytotoxicity in BALB/c mice splenic macrophages involving reactive oxygen species generation. DNA gel, Hoechst 33342, annexin-V and TUNEL assay documented macrophage death induced by 21
kb plasmid bearing isolates to be apoptotic in nature. Apoptosis induced by the plasmid bearing isolates involved initiator caspase-8 and caspase-9 and executed by effector caspase-3. ELISA revealed the wild-type isolate as weak inducer of pro-inflammatory cytokine IL-1β. Oral infection with wild-type isolates caused systemic infection in BALB/c mice. With plasmid curing the isolate looses several virulence attributes including cytotoxic potential. The cured isolate induced significant amounts of IL-1β from infected macrophages, disseminated into Peyer's patches, spleen and liver but never attained the bacterial loads recorded with wild-type isolates and were rapidly cleared. Transformation of 21
kb plasmid helped the cured bacteria regain wild-type virulence attributes, apoptotic potential and ability to cause systemic infection in mice. Thus the 21
kb plasmid is a virulence factor in mice. It helps in suppressing the production of pro-inflammatory cytokine IL-1β and induced apoptosis of host macrophages enabling
A. hydrophila to evade host immune responses and establish systemic infection in mice.