The capability of catabolic utilization of N-acetylneuraminic acid, a sialic acid, is essential for Vibrio vulnificus pathogenesis.
N-acetylneuraminic acid (Neu5Ac, sialic acid) could provide a good substrate for enteropathogenic bacteria in the intestine, when the bacteria invade and colonize in human gut. In order to analyze the role of Neu5Ac catabolism in Vibrio vulnificus pathogenesis, a mutant with disruption of the nanA gene encoding Neu5Ac lyase was constructed by allelic exchanges. The nanA mutant was not able to utilize Neu5Ac as a sole carbon source and revealed an altered colony morphotype with reduced opacity in the presence of Neu5Ac. Compared to the wild type, the nanA mutant exhibited a low level of cytotoxicity toward INT-407 epithelial cells in vitro and reduced virulence in a mouse model. The disruption of nanA also resulted in a substantial decrease in histopathological damage in jejunum and colon tissues from the mouse intestine. These results indicated that NanA plays an important role in V. vulnificus pathogenesis. In addition, the nanA mutant was significantly diminished in growth with and adherence to INT-407 epithelial cells in vitro, and was defective for intestinal colonization, reflecting the impaired ability of the mutant to grow and survive with, persist in, and adhere to the intestine in vivo. Consequently, the combined results suggest that NanA and the capability of catabolic utilization of Neu5Ac contribute to V. vulnificus virulence by ensuring growth, adhesion, and survival during infection.
Jeong
Hee Gon
HG
Department of Agricultural Biotechnology, Center for Agricultural Biomaterials, Research institute for Agriculture and Life Sciences, Seoul National University, South Korea.
Oh
Man Hwan
MH
Kim
Byoung Sik
BS
Lee
Min Young
MY
Han
Ho Jae
HJ
Choi
Sang Ho
SH
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D002460:Cell Line; D003106:Colon / Q000473:pathology; D015169:Colony Count, Microbial; D004847:Epithelial Cells / Q000382:microbiology; D055786:Gene Knockout Techniques; D006801:Humans; D007583:Jejunum / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D007652:Oxo-Acid-Lyases / Q000235:genetics; D014735:Vibrio Infections / Q000382:microbiology*; D041261:Vibrio vulnificus / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence
D001426:Bacterial Proteins; D007652:Oxo-Acid-Lyases; C018728:N-acetylneuraminate lyase; D019158:N-Acetylneuraminic Acid