Temperature triggers immune evasion by Neisseria meningitides

Edmund Loh, Elisabeth Kugelberg, Alexander Tracy, Qian Zhang, Bridget Gollan,

 Helen Ewles, Ronald Chalmers, Vladimir Pelicic & Christoph M. Tang

Nature 502, 237–240, October 10, 2013

Speaker: Feng Ru Hung (洪鳳嬬)                                          Time: 13:10~14:00, Mar. 12, 2013

Commentator: Dr. Ching-Hao Teng (鄧景浩 博士)     Place: Room 601

Abstract:

    Neisseria meningitidis, a Gram-negative pathogen existing in the human nasopharynx, can cause bacterial meningitis and sepsis. Effective complement system is important for host resistance to this pathogen, but it develops diverse mechanisms to evade this attack, including expression of a polysaccharide capsule, sialylation of lipopolysaccharides, and binding with human complement regulator, factor H¹. To identify the factors involved in serum resistance, the authors passaged N. meningitides in 6% human serum, and they obtained several strains that became resistant to complement-mediated killing. Five of them have lost one copy of a duplicated 8-nucleotide sequence (TATACTTA, 8 bps) located at the 5’ untranslated region (5’ UTR) of the mRNA of cssA (encoding capsule biosynthesis). Deletion of one of the two 8 bps (D8) resulted in increased CssA and capsule expression, indicating that the 8 bps regulated CssA expression. However, the css mRNA level in the D8 mutant was not affected suggesting that the effect is post-transcriptional. The 5’ UTR of css mRNA, including the ribosome-binding site, was predicted to form a stem-loop structure that may act like an RNA thermosensor and regulate translation initiation in response to temperature change². Compared to the wild-type strain, the D8 mutant expressed higher amount of capsule at low temperatures, suggesting that the 8 bps might be involved in inhibiting translation at low temperatures. Further, factor H binding protein and Lst(necessary for lipopolysaccharide sialylation), factors involved in immune escape, were upregulated in the wild-type strain with increasing temperature from 30 ^oC to 42 ^oC. In addition, the bacteria that had been incubated at 37 ^oC were significantly more resistant to complement than those incubated at 30 ^oC. Therefore, increased host temperature is a danger signal for N. meningitides to trigger the mechanisms of immune evasion.

References:

1. Schneider M. C. et al. (2007). Interactions between Neisseria meningitidis and the complement system. Trends Microbiol. 15, 233–240.

2. Johansson J. et al. (2002). An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes. Cell 110, 551–561.