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High Levels of Cyclic Di-GMP in Klebsiella pneumoniae Attenuate Virulence in the Lung.

ABSTRACT: The bacterial second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) has been shown to influence the expression of virulence factors in certain pathogenic bacteria, but little is known about its activity in the increasingly antibiotic-resistant pathogen Klebsiella pneumoniae Here, the expression in K. pneumoniae of a heterologous diguanylate cyclase increased the bacterial c-di-GMP concentration and attenuated pathogenesis in murine pneumonia. This attenuation remained evident in mice lacking the c-di-GMP sensor STING, indicating that the high c-di-GMP concentration exerted its influence not on host responses but on bacterial physiology. While serum resistance and capsule expression were unaffected by the increased c-di-GMP concentration, both type 3 and type 1 pili were strongly upregulated. Importantly, attenuation of K. pneumoniae virulence by high c-di-GMP levels was abrogated when type 1 pilus expression was silenced. We conclude that increased type 1 piliation may hamper K. pneumoniae virulence in the respiratory tract and that c-di-GMP signaling represents a potential therapeutic target for antibiotic-resistant K. pneumoniae in this niche.

SUBMITTER: Rosen DA

PROVIDER: S-EPMC5778367 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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High Levels of Cyclic Di-GMP in Klebsiella pneumoniae Attenuate Virulence in the Lung.

Rosen David A DA Twentyman Joy J Hunstad David A DA

Infection and immunity 20180122 2

The bacterial second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) has been shown to influence the expression of virulence factors in certain pathogenic bacteria, but little is known about its activity in the increasingly antibiotic-resistant pathogen <i>Klebsiella pneumoniae</i> Here, the expression in <i>K. pneumoniae</i> of a heterologous diguanylate cyclase increased the bacterial c-di-GMP concentration and attenuated pathogenesis in murine pneumonia. This attenuation remained evident ...[more]

PMID: 29158434

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Dataset Information

High Levels of Cyclic Di-GMP in Klebsiella pneumoniae Attenuate Virulence in the Lung.

Publications

High Levels of Cyclic Di-GMP in Klebsiella pneumoniae Attenuate Virulence in the Lung.

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