The Type VI Secretion System Engages a Redox-Regulated Dual-Functional Heme Transporter for Zinc Acquisition

Si, Meiru; Wang, Yao; Zhang, Bing; Zhao, Chao; Kang, Yiwen; Bai, Haonan; Wei, Dawei; Zhu, Lingfang; Zhang, Lei; Dong, Tao; Shen, Xihui

doi:10.1016/j.celrep.2017.06.081

Cited by 102 publications

(97 citation statements)

References 32 publications

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“…Evidence accumulated in recent years has demonstrated that G. mellonella larvae can be used as an attractive alternative model to identify the virulence of various pathogens (42,(47)(48)(49)(50). In this study, we investigated the extent to which the virulence factors required for pathogenesis in both ducklings and G. mellonella larvae overlap.…”

Section: Discussionmentioning

confidence: 99%

New Perspectives on Galleria mellonella Larvae as a Host Model Using Riemerella anatipestifer as a Proof of Concept

Liu

Huang

et al. 2019

Infect Immun

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Galleria mellonella larvae have been used as a host model to study interactions between pathogens and hosts for several years. However, whether the model is useful to interrogate Riemerella anatipestifer infection biology remained unknown. This study aimed to exploit the potential of G. mellonella larvae and reveal their limitations as a host model for R. anatipestifer infection. G. mellonella larvae were shown to be effective for virulence evaluations of different R. anatipestifer strains. Furthermore, the virulent strain R. anatipestifer CH-1 had a stronger ability to proliferate than the attenuated strain R. anatipestifer ATCC 11845 in both G. mellonella larvae and ducklings. Unconventionally it was shown that G. mellonella larvae cannot be used to evaluate the efficacy of antimicrobials and their combinations. Additionally, it was shown that certain virulence factors, such as OmpA (B739_0861), B739_1208, B739_1343, and Wza (B739_1124), were specific only for ducklings, suggesting that G. mellonella larvae must be cautiously used to identify virulence factors of R. anatipestifer. Evaluation of heme uptake-related virulence genes, such as tonB1 and tonB2, required preincubating the strains with hemoglobin before infection of G. mellonella larvae since R. anatipestifer cannot obtain a heme source from G. mellonella larvae. In conclusion, this study revealed the applicability and limitations of G. mellonella as a model with which to study the pathogen-host interaction, particularly in the context of R. anatipestifer infection.A fter Robert Koch's work, Stanley Falkow established the molecular version of Koch's postulates, which have guided the study of the microbial virulence determinants in infectious diseases since the late 1980s (1). One of the key purposes of the molecular version of Koch's postulates is to test whether a microorganism is attenuated when a candidate virulence gene is inactivated. Thus, the use of animal models to identify the virulence factors of pathogens is indispensable. However, animal models are accompanied by ethical problems and cannot be used in large numbers for statistical analysis. Recently, nonmammalian models, including Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, and larvae of the greater wax moth, Galleria mellonella, have been used for biological research (2-4). These organisms share many advantages over mammalian models, including being easy to obtain, cost-effective, and more ethically acceptable. However, the optimal temperature for C. elegans, D. melanogaster, and Danio rerio is below 28°C (5, 6). These models are defective since the optimum temperature for most mammal pathogens is 37°C. In contrast, the G. mellonella larva model is able to survive at 37°C. Moreover, the immune system of G. mellonella larvae

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Section: Discussionmentioning

confidence: 99%

New Perspectives on Galleria mellonella Larvae as a Host Model Using Riemerella anatipestifer as a Proof of Concept

Liu

Huang

et al. 2019

Infect Immun

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“…Interestingly, recently has been shown that in response to oxidative stress, T6SS from Yersinia pseudotuberculosis and Burkholderia thailandensis secrete effectors involved in ion uptake. The ion import is further mediated by ABC and/or TonB-family proteins [35][36][37].…”

Section: Genomic Context Of T6ss Genesmentioning

confidence: 99%

Insights into Klebsiella pneumoniae type VI secretion system transcriptional regulation

Barbosa

Lery

2019

BMC Genomics

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Background Klebsiella pneumoniae (KP) is an opportunistic pathogen that mainly causes respiratory and urinary tract infections. The frequent occurrence of simultaneously virulent and multiple drug-resistant isolates led WHO to include this species in the list of top priorities for research and development of therapeutic alternatives. The comprehensive knowledge of the molecular mechanisms underlying KP virulence may lead to the proposal of more efficient and specific drugs. One of its virulence factors is the Type VI Secretion System (T6SS), which contributes to bacterial competition, cell invasion and in vivo colonisation. Despite the few studies showing the involvement of T6SS in KP pathogenesis, little is known concerning the regulation of its expression. The understanding of regulatory mechanisms may give more clues about the function of the system and the possibilities of future interference in this process. This work aimed to standardise the annotation of T6SS genes in KP strains and identify mechanisms of their transcriptional regulation through computational predictions. Results We analyzed the genomes of Kp52.145, HS11286 and NTUH-K2044 strains to perform a broad prediction and re-annotation of T6SS genes through similarity searches, comparative and linear discriminant analysis. 38 genes were found in Kp52.145, while 29 in HS11286 and 30 in NTUH-K2044. Genes coding for iron uptake systems are encoded in adjacencies of T6SS, suggesting that KP T6SS might also play a role in ion import. Some of the T6SS genes are comprised in syntenic regions. 17 sigma 70-dependent promoter regions were identified in Kp52.145, 12 in HS11286 and 12 in NTUH-K2044. Using VirtualFootprint algorithm, binding sites for 13 transcriptional regulators were found in Kp52.145 and 9 in HS11286 and 17 in NTUH-K2044. Six of them are common to the 3 strains: OxyR, H-NS, RcsAB, GcvA, Fis, and OmpR. Conclusions The data presented herein are derived from computational analysis. Although future experimental studies are required to confirm those predictions, they suggest that KP T6SS might be regulated in response to environmental signals that are indeed sensed by the bacteria inside the human host: temperature (H-NS), nutrition-limitation (GcvA and Fis), oxidative stress (OxyR) and osmolarity (RscAB and OmpR). Electronic supplementary material The online version of this article (10.1186/s12864-019-5885-9) contains supplementary material, which is available to authorized users.

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“…in Burkholderia thailandenss was found to secrete a proteinaceous zincophore, which interacts with the outer membrane heme transporter to import zinc under oxidative stress [30]. Given that the transcriptional changes of other zinc importers, such as znu and zip, were not observed in the current study, we postulated that T6SS also plays an important role in zinc transport in P. fluorescens, the downregulation of which reduced the transport of zinc across the outer membrane.…”

Section: Strainmentioning

confidence: 64%

Determining the different mechanisms used by Pseudomonas strains to cope with minimal inhibitory concentrations of zinc via comparative transcriptomic and metabolic analyses

P¹,

Chen²,

Liao³

et al. 2020

Preprint

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Background Pseudomonas is one of the most diverse bacterial genera identified in soil, water, plants and clinical samples. Genome sequence analysis has indicated that this genus can be clustered into three lineages and ten groups. Each group can adopt different mechanisms to thrive under zinc-depleted or high-zinc conditions, two environments that are frequently encountered during their environmental propagation. Results The response mechanisms of three prominent Pseudomonas strains (Pseudomonas aeruginosa PAO1, Pseudomonas putida KT2440, and Pseudomonas fluorescence ATCC13525T) under high-zinc condition were compared using RNA-seq and ultra-performance liquid chromatography–tandem mass spectrometry analysis. Results demonstrated that the three strains shared only minimal similarity at the transcriptional level. Only four genes responsible for zinc efflux were commonly upregulated. P. aeruginosa PAO1 specifically downregulated the operons involved in siderophore synthesis and the genes that encode ribosomal protein, while upregulated the genes associated with antibiotic efflux and cell envelope biosynthesis. The membrane transporters in P. putida KT2440 were globally downregulated, indicating changes in cell permeability. Compared with P. aeruginosa PAO1 and P. putida KT2440, the most remarkable transcriptional variation in P. fluorescence ATCC13525 is the significant downregulation of the type VI secretion system. Metabolite quantitative analysis showed that low concentrations of the metabolites involved in central carbon metabolism and amino acid synthesis were detected in the three strains. Dipeptides containing branched-chain amino acids seems played an important role in alleviating stress caused by zinc ions. Conclusion The exclusion of cytoplasmic ions and reducing the intrusion of excess zinc are equally important for P. aeruginosa, P. putida, and P. fluorescence to withstand external zinc stress. Although similar metal efflux systems were commonly upregulated, these three strains apparently used different pathways to reduce zinc entry. In addition, zinc treatment can increase the difficulties of scavenging P. aeruginosa from its colonisation area, and reduce the effectiveness of P. fluorescence as a biocontrol agent.

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The Type VI Secretion System Engages a Redox-Regulated Dual-Functional Heme Transporter for Zinc Acquisition

Cited by 102 publications

References 32 publications

New Perspectives on Galleria mellonella Larvae as a Host Model Using Riemerella anatipestifer as a Proof of Concept

New Perspectives on Galleria mellonella Larvae as a Host Model Using Riemerella anatipestifer as a Proof of Concept

Insights into Klebsiella pneumoniae type VI secretion system transcriptional regulation

Determining the different mechanisms used by Pseudomonas strains to cope with minimal inhibitory concentrations of zinc via comparative transcriptomic and metabolic analyses

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