Vibrio cholerae VC1741 (PsrA) enhances the colonization of the pathogen in infant mice intestines in the presence of the long-chain fatty acid, oleic acid

Yang, Shuang; Xi, Daoyi; Wang, Xiaochen; Li, Yuehua; Li, Yujia; Yan, Junxiang; Cao, Bihua

doi:10.1016/j.micpath.2020.104443

Cited by 12 publications

(10 citation statements)

References 26 publications

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“…Utilization of exogenous fatty acids remodels the phospholipid bilayer in Vibrio spp . (61, 62, 113) and has an impact on pathogenicity, motility, and antibiotic resistance via unknown mechanisms (62). Our work demonstrates that: i) toxT expression is enhanced in the presence of α-linolenic acid; ii) TcpP levels are significantly elevated in the presence of α-linolenic acid; iii) the tcpP transcript level is not increased with exogenous α-linolenic acid; iiiv) TcpP and TcpH avidly associate within detergent resistant membranes (DRM; hypothesized to be lipid-ordered domains) in the presence of α-linolenic acid; v) TcpP-TcpH interaction is important for inhibition of RIP; And vi) enhanced toxT expression in the presence of α-linolenic acid is dependent on co-association of TcpP and TcpH in the DRM membrane fraction.…”

Section: Discussionmentioning

confidence: 99%

An essential host dietary fatty acid stimulates TcpH inhibition of TcpP proteolysis enabling virulence gene expression in Vibrio cholerae

Demey

Sinha

DiRita

2022

Preprint

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Vibrio cholerae is a Gram-negative gastrointestinal pathogen responsible for the diarrheal disease cholera. Expression of key virulence factors, cholera toxin and toxin-coregulated pilus, is regulated indirectly by two single-pass membrane-localized transcription regulators (MLTR), ToxR and TcpP, that promote expression of the transcription activator toxT. TcpP abundance and activity are controlled by TcpH, a single-pass transmembrane protein, which protects TcpP from a two-step proteolytic process known as regulated intramembrane proteolysis (RIP). The mechanism of TcpH mediated protection of TcpP represents a major gap in our understanding of V. cholerae pathogenesis. Absence of tcpH leads to unimpeded degradation of TcpP in vitro and a colonization defect in a neonate mouse model of V. cholerae colonization. Here, we show that TcpH protects TcpP from RIP via direct interaction. We also demonstrate that a dietary fatty acid, α-linolenic acid, promotes TcpH-dependent inhibition of RIP via co-association of TcpP and TcpH molecules within detergent-resistant membranes (DRMs; also known as lipid rafts) in a mechanism requiring the TcpH transmembrane domain. Taken together our data support a model where V. cholerae cells use exogenous α-linolenic acid to remodel the phospholipid bilayer in vivo, leading to co-association of TcpP and TcpH within DRMs where RIP of TcpP is inhibited by TcpH, thereby promoting V. cholerae pathogenicity.Significance StatementV. cholerae continues to pose a significant global burden on health infection millions of people every year resulting in ∼100,000 deaths annually. The importance of toxT gene expression in V. cholerae pathogenesis has been well established. Our results show that TcpP, one of the major regulators of toxT gene expression, is protected from proteolysis by TcpH, via direct interaction, in the presence of α-linolenic acid, an essential dietary fatty acid. Here we identify a physiological relevant host factor that stimulates V. cholerae pathogenicity via TcpH-dependent antagonism of TcpP proteolysis.

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Section: Discussionmentioning

confidence: 99%

An essential host dietary fatty acid stimulates TcpH inhibition of TcpP proteolysis enabling virulence gene expression in Vibrio cholerae

Demey

Sinha

DiRita

2022

Preprint

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“…qRT-PCR was conducted in the Applied Biosystems 7500 sequence detection system with SYBR green fluorescence dye. For normalization, 16S rRNA was utilized [ 42 ]. The 2 –ΔΔCT method calculated fold change in the assessed gene expression [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

A novel quorum sensing regulator LuxT contributes to the virulence of Vibrio cholerae

Li,

Yan,

et al. 2023

Virulence

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Vibrio cholerae is a waterborne bacterium that primarily infects the human intestine and causes cholera fatality. Quorum sensing (QS) negatively regulates the expression of V. cholerae virulence gene. However, the primary associated mechanisms remain undetermined. This investigation identified a new QS regulator from the TetR family, LuxT, which increases V. cholerae virulence by directly inhibiting hapR expression. HapR is a master QS regulator that suppresses virulence cascade expression. The expression of luxT increased 4.8-fold in the small intestine of infant mice than in Luria-Bertani broth. Δ luxT mutant strain revealed a substantial defect in the colonizing ability of the small intestines. At low cell densities, the expression level of hapR was upregulated by luxT deletion, suggesting that LuxT can suppress hapR transcription. The electrophoretic mobility shift analysis revealed that LuxT directly binds to the hapR promoter region. Furthermore, luxT expression was upregulated by the two-component system ArcB/ArcA, which responses to changes in oxygen levels in response to the host’s small intestine’s anaerobic signals. In conclusion, this research reveals a novel cell density-mediated virulence regulation pathway and contributes to understanding the complex association between V. cholerae virulence and QS signals. This evidence furnishes new insights for future studies on cholerae’s pathogenic mechanisms.

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“…qRT-PCR was performed on an Applied Biosystems 7500 sequence detection system with SYBR green fluorescence dye. The 16 s rRNA gene was used as the reference control for sample normalization [ 37 ]. Table 2 lists the primers used in this study.…”

Section: Methodsmentioning

confidence: 99%

“…A sequence encoding a ArcA/CytR/CRP-His 6 fusion protein was cloned into vector pET-28a, expressed in E. coli BL21 (DE3), and purified using an Ni–NTA-Sefinose Column in accordance with the protocol provided by the manufacturer [ 37 , 39 ]. EMSA was performed by adding increasing amounts of purified phosphorylated ArcA protein (0, 1.5, 3.0, 4.5, and 6.0 µM or 0, 0.6, 1.2, 1.8 and 2.4 µM) to cytR or flrA DNA fragments (50 ng) in a binding buffer [10 mM Tris–HCl (pH 8.0), 1 mM EDTA, 1 mM DTT, 50 mM KCl, 50 μg/mL BSA, 10% glycerol] supplemented with 20 nM acetyl phosphate [ 39 ], followed by incubation for 40 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

The global regulators ArcA and CytR collaboratively modulate Vibrio cholerae motility

Yan

Guo

et al. 2022

BMC Microbiol

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Background Vibrio cholerae, a Gram-negative bacterium, is highly motile owing to the presence of a single polar flagellum. The global anaerobiosis response regulator, ArcA regulates the expression of virulence factors and enhance biofilm formation in V. cholerae. However, the function of ArcA for the motility of V. cholerae is yet to be elucidated. CytR, which represses nucleoside uptake and catabolism, is known to play a chief role in V. cholerae pathogenesis and flagellar synthesis but the mechanism that CytR influences motility is unclear. Results In this study, we found that the ΔarcA mutant strain exhibited higher motility than the WT strain due to ArcA directly repressed flrA expression. We further discovered that CytR directly enhanced fliK expression, which explained why the ΔcytR mutant strain was retarded in motility. On the other hand, cytR was a direct ArcA target and cytR expression was directly repressed by ArcA. As expected, cytR expression was down-regulated. Conclusions Overall, ArcA plays a critical role in V. cholerae motility by regulating flrA expression directly and fliK indirectly in the manner of cytR.

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Vibrio cholerae VC1741 (PsrA) enhances the colonization of the pathogen in infant mice intestines in the presence of the long-chain fatty acid, oleic acid

Cited by 12 publications

References 26 publications

An essential host dietary fatty acid stimulates TcpH inhibition of TcpP proteolysis enabling virulence gene expression in Vibrio cholerae

An essential host dietary fatty acid stimulates TcpH inhibition of TcpP proteolysis enabling virulence gene expression in Vibrio cholerae

A novel quorum sensing regulator LuxT contributes to the virulence of Vibrio cholerae

The global regulators ArcA and CytR collaboratively modulate Vibrio cholerae motility

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