Dataset Information

Mice Lacking Fatty Acid-Binding Protein 5 Are Resistant to Listeria monocytogenes.

ABSTRACT: To investigate the role of fatty acid-binding protein 5 (FABP5) in infectious diseases, FABP5-deficient mice were challenged with Listeria monocytogenes, a facultative intracellular bacterial pathogen. Interestingly, FABP5-deficient animals were able to clear the infection within 3 days whereas control wild-type (WT) animals showed comparatively higher bacterial burdens in the liver and spleen. Sections of infected tissues showed an increase in inflammatory foci in WT mice compared to FABP5-deficient mice. FABP5-deficient mice had lower circulating inflammatory cytokines and increased inducible nitric oxide synthase production. FABP5-deficient mouse bone marrow-derived macrophages produced higher levels of nitrite anion than their WT counterparts in response to various stimuli. Additionally, in contrast to FABP5-/- mice, transgenic mice overexpressing FABP5 in myeloid cells (LysM-Cre driven) showed decreased survival rates and increased bacterial burden and inflammatory cytokines. Overall, these findings suggest that increased FABP5 levels correlate with a higher L. monocytogenes bacterial burden and elevated subsequent inflammation.

SUBMITTER: Rao DM

PROVIDER: S-EPMC6758948 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Mice Lacking Fatty Acid-Binding Protein 5 Are Resistant to Listeria monocytogenes.

Rao Deviyani M DM Phan Della T DT Choo Michelle J MJ Owen Amie L AL Perraud Anne-Laure AL Gally Fabienne F

Journal of innate immunity 20190318 6

To investigate the role of fatty acid-binding protein 5 (FABP5) in infectious diseases, FABP5-deficient mice were challenged with Listeria monocytogenes, a facultative intracellular bacterial pathogen. Interestingly, FABP5-deficient animals were able to clear the infection within 3 days whereas control wild-type (WT) animals showed comparatively higher bacterial burdens in the liver and spleen. Sections of infected tissues showed an increase in inflammatory foci in WT mice compared to FABP5-defi ...[more]

PMID: 30884482

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Project description:Naturally occurring free fatty acids (FFAs) are recognized as potent antimicrobial agents that also affect the production of virulence factors in bacterial pathogens. In the foodborne pathogen Listeria monocytogenes, some medium- and long-chain FFAs act as antimicrobial agents as well as signaling compounds, causing a repression of transcription of virulence genes. We previously observed that the master virulence regulator PrfA is involved in both the antimicrobial and virulence-inhibitory response of L. monocytogenes to selected FFAs, but the underlying mechanisms are presently unknown. Here, we present a systematic analysis of the antimicrobial and PrfA-inhibitory activities of medium- and long-chain FFAs of various carbon chain lengths and degrees of saturation. We observed that exposure to specific antimicrobial and nonantimicrobial FFAs prevented PrfA-dependent activation of virulence gene transcription and reduced the levels of PrfA-regulated virulence factors. Thus, an antimicrobial activity was not compulsory for the PrfA-inhibitory ability of an FFA. In vitro binding experiments revealed that PrfA-inhibitory FFAs were also able to prevent the constitutively active variant PrfA* from binding to the PrfA box in the promoter region of the virulence gene hly, whereas noninhibitory FFAs did not affect its ability to bind DNA. Notably, the unsaturated FFAs inhibited the DNA binding activity of PrfA* most efficiently. Altogether, our findings support a model in which specific FFAs orchestrate a generalized reduction of the virulence potential of L. monocytogenes by directly targeting the key virulence regulator PrfA.IMPORTANCEListeria monocytogenes is a Gram-positive pathogen able to cause foodborne infections in humans and animals. Key virulence genes in L. monocytogenes are activated by the transcription regulator PrfA, a DNA binding protein belonging to the CRP/FNR family. Various signals from the environment are known to affect the activity of PrfA, either positively or negatively. Recently, we found that specific medium- and long-chain free fatty acids act as antimicrobial agents as well as signaling compounds in L. monocytogenes Here, we show that both antimicrobial and nonantimicrobial free fatty acids inhibit PrfA-dependent activation of virulence gene transcription by interfering with the DNA binding activity of PrfA. Our findings suggest that free fatty acids could be candidates for alternative therapies against L. monocytogenes.

Dataset Information

Mice Lacking Fatty Acid-Binding Protein 5 Are Resistant to Listeria monocytogenes.

Publications

Mice Lacking Fatty Acid-Binding Protein 5 Are Resistant to Listeria monocytogenes.

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