Roles of the Hcp family proteins in the pathogenicity of <i>Salmonella typhimurium</i> 14028s

Wang, Ping; Dong, Jun-Fang; Li, Ren-Qing; Li, Lei; Zhou, Qinghua

doi:10.1080/21505594.2020.1854538

Cited by 9 publications

(6 citation statements)

References 51 publications

(65 reference statements)

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“…In addition to its antibacterial and anti-eukaryotic effects, T6SS also plays a role in the function of multiple virulence factors. 45–47 The effect of Tle1 Vc on bacterial motility and biofilm formation was tested, and the results showed no significant difference in biofilm formation between the wild-type and Δ tle1 Vc strains. However, the motility of the Δ tle1 Vc mutant was noticeably decreased compared to that of the wild-type, and this phenotype could be restored after the Δ tle1 Vc mutant was complemented with tle1 Vc (Δ tle1 Vc +pTle1 Vc ) ( Figure 7a ).…”

Section: Resultsmentioning

confidence: 99%

The phospholipase effector Tle1 ^Vc promotes Vibrio cholerae virulence by killing competitors and impacting gene expression

et al. 2023

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Vibrio cholerae utilizes the Type VI secretion system (T6SS) to gain an advantage in interbacterial competition by delivering anti-prokaryotic effectors in a contact-dependent manner. However, the impact of T6SS and its secreted effectors on physiological behavior remains poorly understood. In this study, we present Tle1 Vc , a phospholipase effector in atypical pathogenic V. cholerae E1 that is secreted by T6SS via its interaction with VgrG1 E1 . Tle1 Vc contains a DUF2235 domain and belongs to the Tle1 (type VI lipase effector) family. Bacterial toxicity assays, lipase activity assays and site-directed mutagenesis revealed that Tle1 Vc possessed phospholipase A 1 activity and phospholipase A 2 activity, and that Tle1 Vc -induced toxicity required a serine residue (S356) and two aspartic acid residues (D417 and D496). Cells intoxication with Tle1 Vc lead to membrane depolarization and alter membrane permeability. Tli1 tox- , a cognate immunity protein, directly interacts with Tle1 Vc to neutralize its toxicity. Moreover, Tle1 Vc can kill multiple microorganisms by T6SS and promote in vivo fitness of V. cholerae through mediating antibacterial activity. Tle1 Vc induces bacterial motility by increasing the expression of flagellar-related genes independently of functional T6SS and the tit-for-tat (TFT) response, where Pseudomonas aeruginosa uses its T6SS-H1 cluster to counterattack other offensive attackers. Our study also demonstrated that the physical puncture of E1 T6SS can induce a moderate TFT response, which is essential to the Tle1 Vc -mediated strong TFT response, maximizing effector functions. Overall, our study characterized the antibacterial mechanism of phospholipase effector Tle1 Vc and its multiple physiological significance.

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Section: Resultsmentioning

confidence: 99%

The phospholipase effector Tle1 ^Vc promotes Vibrio cholerae virulence by killing competitors and impacting gene expression

et al. 2023

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“…The current study revealed that Hcp also functions as an exported effector and chaperone of Type VI secretion substrates in Gram-negative bacteria [2,10,36]. Hcp has been proven to be involved in bacterial motility, adherence, and cytotoxicity to host cells by regulating the flagellar system in various pathogens [12,13,15,16]. However, for Vibrio alginolyticus, the roles of Hcp on bacterial motility remains unknow.…”

Section: Loss Of Hcp2 Reduced the Swarming Motility Of Vibrio Alginol...mentioning

confidence: 88%

“…[11][12][13]. More importantly, there are reports showing that the deletion of the T6SS genomic island (GI) or its other core components, such as Hcp, will result in less-motile, lower-virulence bacteria than wild-type strains by regulating the flagellar system at the levels of transcription and translation in several species [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Roles of Hcp2, a Hallmark of T6SS2 in Motility, Adhesive Capacity, and Pathogenicity of Vibrio alginolyticus

Wu,

Tang,

Wang

et al. 2023

Microorganisms

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The type VI secretion system (T6SS) is a large secretory device, widely found in Gram-negative bacteria, which plays important roles in virulence, bacterial competition, and environmental adaptation. Vibrio alginolyticus (V. alginolyticus) is an opportunistic pathogen that causes vibriosis in aquaculture animals. V. alginolyticus possesses two type VI secretion systems (named the T6SS1 and T6SS2), but their functions remain largely unclear. In this paper, the roles of the core component of the T6SS2 cluster of V. alginolyticus HY9901, hemolysin-coregulated protein2 coding gene hcp2, are reported. Deletion of hcp2 clearly impaired the swarming motility, adhesive capacity, and pathogenicity of V. alginolyticus against zebrafish. Furthermore, transmission electron microscopy (TEM) found that the abnormal morphology of flagellum filament in the hcp2 mutant strain could be partially restored by hcp2 complementarity. By proteomic and RT-qPCR analysis, we confirmed that the expression levels of flagellar flagellin and assembly-associated proteins were remarkably decreased in an hcp2 mutant strain, compared with the wild-type strain, and could be partially restored with a supply of hcp2. Accordingly, hcp2 had a positive influence on the transcription of flagellar regulons rpoN, rpoS, and fliA; this was verified by RT-qPCR. Taken together, these results suggested that hcp2 was involved in mediating the motility, adhesion, and pathogenicity of Vibrio alginolyticus through positively impacting its flagellar system.

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“…In this study, we identified and isolated WT W24 ( Figure S2 ) from the feces of diarrheal piglets from a pig farm in Yunnan, China, and performed a sequencing analysis, which has not been published yet. Hcp1, a bacterial-derived toxin protein of the T6SS, can also be secreted into host cells to cause damage [ 28 , 29 ]. When mice were infected with WT W24, we found high levels of TNF-α, IFN-γ, IL-1β, and IL-18 in their blood, livers, and kidneys.…”

Section: Discussionmentioning

confidence: 99%

Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis

Wang

Chen

et al. 2023

Toxins

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Hemolysin-coregulated protein 1 (Hcp1) is an effector released by the type VI secretion system (T6SS) in certain pathogenic strains of Escherichia coli (E. coli) that causes apoptosis and contributes to the development of meningitis. The exact toxic consequences of Hcp1 and whether it intensifies the inflammatory response by triggering pyroptosis are yet unknown. Here, utilizing the CRISPR/Cas9 genome editing method, we removed the gene expressing Hcp1 from wild-type E. coli W24 and examined the impact of Hcp1 on E. coli virulence in Kunming (KM) mice. It was found that Hcp1-sufficient E. coli was more lethal, exacerbating acute liver injury (ALI) and acute kidney injury (AKI) or even systemic infections, structural organ damage, and inflammatory factor infiltration. These symptoms were alleviated in mice infected with W24Δhcp1. Additionally, we investigated the molecular mechanism by which Hcp1 worsens AKI and found that pyroptosis is involved, manifested as DNA breaks in many renal tubular epithelial cells. Genes or proteins closely related to pyroptosis are abundantly expressed in the kidney. Most importantly, Hcp1 promotes the activation of the NLRP3 inflammasome and the expression of active caspase-1, thereby cleaving GSDMD-N and accelerating the release of active IL-1β and ultimately leading to pyroptosis. In conclusion, Hcp1 enhances the virulence of E. coli, aggravates ALI and AKI, and promotes the inflammatory response; moreover, Hcp1-induced pyroptosis is one of the molecular mechanisms of AKI.

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Roles of the Hcp family proteins in the pathogenicity of Salmonella typhimurium 14028s

Cited by 9 publications

References 51 publications

The phospholipase effector Tle1 ^Vc promotes Vibrio cholerae virulence by killing competitors and impacting gene expression

The phospholipase effector Tle1 ^Vc promotes Vibrio cholerae virulence by killing competitors and impacting gene expression

Roles of Hcp2, a Hallmark of T6SS2 in Motility, Adhesive Capacity, and Pathogenicity of Vibrio alginolyticus

Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis

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Roles of the Hcp family proteins in the pathogenicity of Salmonella typhimurium 14028s

Cited by 9 publications

References 51 publications

The phospholipase effector Tle1 Vc promotes Vibrio cholerae virulence by killing competitors and impacting gene expression

The phospholipase effector Tle1 Vc promotes Vibrio cholerae virulence by killing competitors and impacting gene expression

Roles of Hcp2, a Hallmark of T6SS2 in Motility, Adhesive Capacity, and Pathogenicity of Vibrio alginolyticus

Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis

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The phospholipase effector Tle1 ^Vc promotes Vibrio cholerae virulence by killing competitors and impacting gene expression

The phospholipase effector Tle1 ^Vc promotes Vibrio cholerae virulence by killing competitors and impacting gene expression