ERVMER34-1

Last update 08 May 2025

Basic Info

Synonyms

Endogenous retroviral envelope protein HEMO, Endogenous retroviral envelope protein HEMO, 48 kDa form, Endogenous retroviral envelope protein HEMO, secreted form

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Introduction

Endogenous envelope proteins originate from retroviral envelope proteins, which mediate receptor recognition and membrane fusion during early infection. Endogenous envelope proteins may have kept, lost or modified their original function during evolution.

100 Clinical Results associated with ERVMER34-1

100 Translational Medicine associated with ERVMER34-1

0 Patents (Medical) associated with ERVMER34-1

Literatures (Medical) associated with ERVMER34-1

01 May 2025·Journal of Biological Chemistry

The Pseudomonas aeruginosa PhuS proximal ligand His-209 triggers a conformational switch in function from DNA binding to heme transfer

Article

Author: Wilks, Angela ; Deredge, Daniel ; Kane, Maureen A ; Montes, Nicholas ; Wilson, Tyree ; Mouriño, Susana ; Krug, Samuel A

Pseudomonas aeruginosa can acquire iron from heme via the heme assimilation system and Pseudomonas heme uptake (Phu) systems. Heme uptake is regulated at the metabolic level by the cytoplasmic protein PhuS that controls heme flux through a heme oxygenase HemO, releasing iron and biliverdin IXβ and IXδ. We have shown PhuS regulates extracellular heme flux, and in its apo-form transcriptionally regulates the iron and heme-dependent small RNAs (sRNAs) PrrF/PrrH. This mutual exclusivity of function is driven by conformational rearrangement of PhuS on heme binding. Herein, we show through a combination of EMSA and fluorescence anisotropy that mutation of the His-209 proximal ligand allows both apo- and holo-PhuS H209A to bind to the prrF1 promoter with significantly lower affinity when compared to PAO1 WT. Hydrogen deuterium exchange coupled to mass spectrometry revealed the apo- and holo-PhuS H209A structures are closer to each other than their WT counterparts and sample a conformational landscape between the apo- and holo-PhuS WT conformations, that is neither optimal for heme transfer nor DNA-binding. Furthermore, quantitative PCR and Western blot analysis of the phuSH209A allelic strain compared to PAO1 WT revealed an uncoupling of the PhuS-HemO dependent regulation of heme flux into the cell that abrogates the heme dependent regulation of the PrrF/PrrH sRNAs. The data supports a model where heme coordination through His-209 drives the conformational switch that determines mutual exclusivity in function of apo- and holo-PhuS. This dual function of PhuS is central to integrating extracellular heme utilization into the PrrF/PrrH sRNA regulatory network critical for P. aeruginosa adaptation within the host.

07 Feb 2025·Journal of Proteome Research

Quantitative LC–MS/MS Analysis of Endogenous Pseudomonas aeruginosa Isomeric Metabolites Biliverdin IX Alpha, Beta, and Delta in Cell Culture Supernatant, Cell Pellet, and Lung Tissue

Article

Author: Krug, Samuel A ; Witt, William T. ; Wilks, Angela ; Barbier, Mariette ; Kane, Maureen A ; Shahzad, Saba

Pseudomonas aeruginosa (Pa) utilizes heme as an iron source from the host during infection. Biliverdin beta and delta (BVIXβ and BVIXδ) are generated by HemO, specific to Pa, while biliverdin alpha is generated from the bacterial BphO system and by mammalian heme oxygenases. Here, we have developed and characterized a quantitative LC-MS/MS assay for the separation of three endogenous isomers, BVIXα, BVIXβ, and BVIXδ. The assay was validated for accuracy, precision, linearity, extraction recovery, solution stability, freeze-thaw stability, benchtop stability, postextraction stability, and nonspecific oxidation of BVIX. The addition of an antioxidant, butylated hydroxytoluene, during sample preparation is needed in order to prevent coupled oxidation from inflating quantitative values of BVIX. The assay development included optimization of a liquid-liquid extraction for bacterial culture supernatants and sample preparation procedures for cell pellets and tissue homogenate to reduce sample demand and automate the extraction procedure in a 96-well format, to enhance extraction throughput. This method was applied to analyze isomer distribution in Pa supernatant, bacterial pellet, and infected lung tissue from Pa-challenged mice. This method can be used in the future for low-volume culture samples, as well as tissue samples, to understand the mechanisms of virulence and inform future drug development.

01 Dec 2024·International Journal of Antimicrobial Agents

Emergence of extensively-drug-resistant hypervirulent Acinetobacter baumannii isolated from patients with bacteraemia: bacterial phenotype and virulence analysis

Article

Author: Kao, Cheng-Yen ; Liu, Chia-Ying ; Zhang, Yen-Zhen ; Chen, Pek Kee ; Lee, Yi-Tzu ; Liu, Yu-Han ; Kuo, Han-Yueh

OBJECTIVESIndividuals infected with extensively-drug-resistant (XDR) Acinetobacter baumannii are difficult to cure and have a high mortality rate. This study compared the genomic and phenotypic differences between XDR and non-multi-drug-resistant (MDR) A. baumannii, and further characterized hypervirulent XDR A. baumannii.METHODSIn total, 1403 acinetobacter isolates were collected from patients with bacteraemia between 1997 and 2015. Antimicrobial susceptibility tests were performed to categorize isolates into non-MDR, MDR and XDR groups. The presence of selected virulence-associated genes was determined by polymerase chain reaction. Bacterial phenotypes, including iron acquisition, biofilm formation, capsule production, and virulence to larvae and mice, were determined.RESULTSMulti-locus sequence typing revealed a high prevalence of sequence type (ST) 2 (81.6%) and ST129 (18.4%) among 49 XDR isolates, and the STs of 18 non-MDR isolates were more diverse. Virulence-associated phenotypic assays showed that XDR isolates had higher iron acquisition ability, greater capsule production, and virulence to Galleria mellonella larvae. However, their ability to form biofilm was lower compared with that of non-MDR isolates. XDR isolates were more likely to have virulence genes (tonB, hemO, abaI and ptk), while non-MDR isolates were more likely to have pld and ompA genes. Twenty-one XDR isolates that had a <20% larvae survival rate after 7 days post-infection were defined as hypervirulent XDR isolates. Among them, isolates 1677 (ST129) and 929-1 (ST2) caused the death of all infected mice within 2 days.CONCLUSIONSome subpopulations of highly-drug-resistant ST2 isolates exhibit high virulence. As such, it is of utmost importance to continue monitoring the spread of hypervirulent XDR A. baumannii isolates.

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ERVMER34-1

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