scholarly journals Protein aggregation in bacteria

2019 ◽  
Vol 44 (1) ◽  
pp. 54-72 ◽  
Author(s):  
Frederic D Schramm ◽  
Kristen Schroeder ◽  
Kristina Jonas
Keyword(s):  
Protein Aggregation ◽  
Stress Resistance ◽  
Protein Quality ◽  
Protein Aggregates ◽  
Protein Homeostasis ◽  
Bacterial Protein ◽  
Bacterial Populations ◽  
Regulate Gene Expression ◽  
Specific Proteins ◽  
Cellular Stresses

ABSTRACT Protein aggregation occurs as a consequence of perturbations in protein homeostasis that can be triggered by environmental and cellular stresses. The accumulation of protein aggregates has been associated with aging and other pathologies in eukaryotes, and in bacteria with changes in growth rate, stress resistance and virulence. Numerous past studies, mostly performed in Escherichia coli, have led to a detailed understanding of the functions of the bacterial protein quality control machinery in preventing and reversing protein aggregation. However, more recent research points toward unexpected diversity in how phylogenetically different bacteria utilize components of this machinery to cope with protein aggregation. Furthermore, how persistent protein aggregates localize and are passed on to progeny during cell division and how their presence impacts reproduction and the fitness of bacterial populations remains a controversial field of research. Finally, although protein aggregation is generally seen as a symptom of stress, recent work suggests that aggregation of specific proteins under certain conditions can regulate gene expression and cellular resource allocation. This review discusses recent advances in understanding the consequences of protein aggregation and how this process is dealt with in bacteria, with focus on highlighting the differences and similarities observed between phylogenetically different groups of bacteria.

scholarly journals FLNC-Associated Myofibrillar Myopathy

2021 ◽  
Vol 7 (3) ◽  
pp. e590
Author(s):  
Rudolf Andre Kley ◽  
Yvonne Leber ◽  
Bertold Schrank ◽  
Heidi Zhuge ◽  
Zacharias Orfanos ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Protein Quality ◽  
Mutational Analysis ◽  
Protein Aggregates ◽  
Ubiquitin Proteasome System ◽  
Protein Accumulation ◽  
Control Mechanisms ◽  
Myofibrillar Myopathy ◽  
Dimerization Domain ◽  
Indel Mutation

ObjectiveTo determine whether a new indel mutation in the dimerization domain of filamin C (FLNc) causes a hereditary myopathy with protein aggregation in muscle fibers, we clinically and molecularly studied a German family with autosomal dominant myofibrillar myopathy (MFM).MethodsWe performed mutational analysis in 3 generations, muscle histopathology, and proteomic studies of IM protein aggregates. Functional consequences of the FLNC mutation were investigated with interaction and transfection studies and biophysics molecular analysis.ResultsEight patients revealed clinical features of slowly progressive proximal weakness associated with a heterozygous c.8025_8030delCAAGACinsA (p.K2676Pfs*3) mutation in FLNC. Two patients exhibited a mild cardiomyopathy. MRI of skeletal muscle revealed lipomatous changes typical for MFM with FLNC mutations. Muscle biopsies showed characteristic MFM findings with protein aggregation and lesion formation. The proteomic profile of aggregates was specific for MFM-filaminopathy and indicated activation of the ubiquitin-proteasome system (UPS) and autophagic pathways. Functional studies revealed that mutant FLNc is misfolded, unstable, and incapable of forming homodimers and heterodimers with wild-type FLNc.ConclusionsThis new MFM-filaminopathy family confirms that expression of mutant FLNC leads to an adult-onset muscle phenotype with intracellular protein accumulation. Mutant FLNc protein is biochemically compromised and leads to dysregulation of protein quality control mechanisms. Proteomic analysis of MFM protein aggregates is a potent method to identify disease-relevant proteins, differentiate MFM subtypes, evaluate the relevance of gene variants, and identify novel MFM candidate genes.

scholarly journals THE ENDOPLASMIC RETICULUM PROTEIN QUALITY CONTROL ADAPTATION IN A LONG-LIVED C. ELEGANS PROTEASOMAL MUTANT

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S99-S99
Author(s):  
Meghna N Chinchankar ◽  
Karl Rodriguez ◽  
Alfred Fisher
Keyword(s):  
Stress Resistance ◽  
Protein Quality ◽  
Underlying Mechanism ◽  
26S Proteasome ◽  
Protein Homeostasis ◽  
Catalytic Core ◽  
C Elegans ◽  
Endoplasmic Reticulum Protein ◽  
Extended Lifespan ◽  
Er Homeostasis

Abstract Protein degradation mechanisms are integral to protein homeostasis. Their reduced efficiency during aging leads to accumulation of misfolded and aggregated proteins which potentiate proteotoxic disorders. Paradoxically, our lab reported that the Caenorhabditis elegans rpn-10(ok1865) proteasome mutant possesses enhanced proteostasis and extended lifespan. RPN-10/PSMD4 is a ubiquitin receptor of the 26S proteasome that targets polyubiquitinated substrates to its catalytic core for degradation. Proteasome dysfunction of the rpn-10 mutant is characterized by reduced, not inhibited, ubiquitin fusion degradation. We ascertained that upregulated autophagy and SKN-1/Nrf-mediated responses partially contribute to the robust rpn-10 mutant phenotype. Further investigation of its underlying mechanism revealed that several ERQC genes are transcriptionally upregulated in the rpn-10 mutant. Thus, we hypothesized that the rpn-10 mutant exhibits improved ER proteostasis which mediates its elevated cellular stress resistance. Accordingly, the rpn-10 mutant shows increased ER stress resistance and altered ER homeostasis. Complementarily, attenuated expression of the aggregation-prone α-1 antitrypsin (ATZ) reporter proves that ER proteostasis is ameliorated in the rpn-10 mutant. Via a genetic screen for suppressors of decreased ATZ aggregation in the rpn-10 mutant, we identified novel player H04D03.3, which is a homolog of the proteasome adaptor ECM29. This suggests that assembly of the rpn-10 mutant proteasome itself critically regulates its ER proteostasis. Moreover, we observed that cytosolic proteostasis and longevity depend on ER master chaperone hsp-3/-4(BiP) and ER ATPase cdc-48.2(p97/VCP), further highlighting ERQC significance in the rpn-10 mutant. Altogether, it appears that mild proteasomal dysfunction induces ERQC adaptation that underlies proteostasis and longevity benefits of the rpn-10 mutant.

scholarly journals Drosophila p38 MAPK Interacts with BAG-3/starvin to Regulate Age-dependent Protein Homeostasis

2019 ◽  
Author(s):  
Sarah M. Ryan ◽  
Michael Almassey ◽  
Amelia M. Burch ◽  
Gia Ngo ◽  
Julia M. Martin ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
P38 Mapk ◽  
Protein Aggregates ◽  
Protein Homeostasis ◽  
Selective Autophagy ◽  
Age Related ◽  
Age Dependent ◽  
Dependent Protein ◽  
Locomotor Behaviors ◽  
The Relationship

SummaryAs organisms age, they often accumulate protein aggregates that are thought to be toxic, potentially leading to age-related diseases. This accumulation of protein aggregates is partially attributed to a failure to maintain protein homeostasis. A variety of genetic factors have been linked to longevity, but how these factors also contribute to protein homeostasis is not completely understood. In order to understand the relationship between aging and protein aggregation, we tested how a gene that regulates lifespan and age-dependent locomotor behaviors, p38 MAPK (p38Kb), influences protein homeostasis as an organism ages. We find that p38Kb regulates age-dependent protein aggregation through an interaction with the Chaperone-Assisted Selective Autophagy complex. Furthermore, we have identified Lamin as an age-dependent target of p38Kb and the Chaperone-Assisted Selective Autophagy complex.

scholarly journals Loss of Elongator- and KEOPS-Dependent tRNA Modifications Leads to Severe Growth Phenotypes and Protein Aggregation in Yeast

2020 ◽  
Author(s):  
Leticia Pollo-Oliveira ◽  
Roland Klassen ◽  
Nick Davis ◽  
Akif Ciftci ◽  
Jo Marie Bacusmo ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Energy Homeostasis ◽  
Protein Quality ◽  
Protein Homeostasis ◽  
Yeast Saccharomyces Cerevisiae ◽  
Subsequent Increase ◽  
Global Function ◽  
Translational Speed ◽  
Speed And Accuracy ◽  
Severe Growth

regulating translational speed and accuracy. Threonylcarbamoyl adenosine (t6A37) and 5-methoxycarbonylmethyl-thiouridine (mcm5s2U34) are critical ASL modifications that have been linked to several human diseases. The model yeast Saccharomyces cerevisiae is viable despite the absence of both modifications, growth is however greatly impaired. The major observed consequence is a subsequent increase in protein aggregates and aberrant morphology. Proteomic analysis of the t6A-deficient strain revealed a global mistranslation leading to protein aggregation without regard to physicochemical properties or t6A-dependent or biased codon usage in parent genes. However, loss of sua5 led to increased expression of soluble proteins for mitochondrial function, protein quality processing/trafficking, oxidative stress response, and energy homeostasis. These results point to a global function for t6A in protein homeostasis very similar to mcm5/s2U modifications.

Abstract 393: The Intercalated Disc Protein Myozap: A Novel Player in Cardiac Proteinopathy

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Ashraf Y Rangrez ◽  
Derk Frank ◽  
Liam Cassidy ◽  
Lynn Christen ◽  
Inka Geurink ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Protein Aggregation ◽  
Protein Quality ◽  
Transcriptome Profiling ◽  
Protein Aggregates ◽  
Intercalated Disc ◽  
Protein Aggregate ◽  
General Role ◽  
Id Protein

Background: A growing number of cardiac muscle diseases are characterized by depositions of misfolded proteins, including cardiac amyloidosis and desmin-releated cardiomyopathy (DRM). The continued presence and chronic accumulation of misfolded or unfolded proteins can lead to aggregation and/or the formation of soluble peptides that are proteotoxic. This in turn leads to compromised protein quality control and precipitates a downward spiral of the cell’s ability to maintain homeostasis and may eventually result in cell death. We recently identified massive protein aggregates in the hearts of transgenic mice overexpressing the intercalated disc (ID) protein myozap (Myozap-tg). We now sought to investigate the precise composition of these aggregates and the role of Myozap in other proteinopathies such as DRM. Methods and Results: We employed multi-dimensional proteomics, transcriptomics, confocal microscopy, and molecular biology approaches to decipher the underlying causes and consequences of protein aggregate formation in Myozap-tg mice. Transcriptome profiling of these mice revealed striking upregulation of autophagy, protein synthesis, and pro-inflammatory pathways, whereas protein degradation pathways were down-regulated. Surprisingly, proteomics analyses revealed Desmin and α-crystallin B (CryAB) as the major constituents of the aggregates, which was further validated by confocal microscopy. Moreover, we identified the presence of toxic preamyloid oligomers in Myozap-tg mouse hearts, a hallmark in many protein aggregation-based diseases including DRM. Most interestingly, we also observed co-localization of Myozap with protein aggregates observed in both transgenic mouse hearts overexpressing mutant Desmin (D7) and mutant CryAB (R120G), as well as in human DRM patients. Conclusion: The present study implies a new role for Myozap, which was previously reported to affect cardiac SRF signaling: (1) Myozap accumulates in various forms of experimental and human protein aggregation cardiomyopathy, suggesting involvement in protein homoestasis. (2) The fact that Myozap is now the third ID protein (after desmin and CryAB) to cause cardiac proteinopathy points to a general role of the ID in its molecular pathogenesis.

Slow rehydration improves the recovery of dried bacterial populations

1992 ◽  
Vol 38 (6) ◽  
pp. 520-525 ◽  
Author(s):  
J. W. Kosanke ◽  
R. M. Osburn ◽  
G. I. Shuppe ◽  
R. S. Smith
Keyword(s):  
Relative Humidity ◽  
Rhizobium Leguminosarum ◽  
Moisture Absorption ◽  
Rhizobium Meliloti ◽  
Bacterial Populations ◽  
Bulk Powder ◽  
Alfalfa Seed ◽  
Powder Samples ◽  
Cellular Stresses ◽  
Rhizobium Leguminosarum Biovar Trifolii

Slow rehydration of bacteria from dried inoculant formulations provided higher viable counts than did rapid rehydration. Estimates were higher when clay and peat powder formulations of Rhizobium meliloti, Rhizobium leguminosarum biovar trifolii, and Pseudomonas putida, with water activities between 0.280 and 0.650, were slowly rehydrated to water activities of approximately 0.992 before continuing the dilution plating sequence. Rhizobium meliloti populations averaged 6.8 × 108 cfu/g and 1328 cfu/alfalfa seed greater when slowly rehydrated from bulk powder and preinoculated seeds, respectively. Bulk powder samples were slowly rehydrated to 0.992 water activity by the gradual addition of diluent, followed by a 10-min period for moisture equilibration. Preinoculated seed samples were placed in an environmental chamber at 24 °C with relative humidity greater than 80% for 1 h to allow moisture absorption. "Upshock," osmotic cellular stresses that occur during rehydration, was reduced when dried microbial formulations were slowly rehydrated and equilibrated before becoming fully hydrated in the dilution plating sequence. These procedures may also be applicable when estimating total viable bacterial populations from dried soil or other dry formulations. Key words: rehydration procedure, microbial rehydration, desiccation, Rhizobium, Pseudomonas.

Allosteric Activation of HtrA Protease DegP by Stress Signals during Bacterial Protein Quality Control

2008 ◽  
Vol 47 (7) ◽  
pp. 1332-1334 ◽  
Author(s):  
Michael Meltzer ◽  
Sonja Hasenbein ◽  
Patrick Hauske ◽  
Nicolette Kucz ◽  
Melisa Merdanovic ◽  
...  
Keyword(s):  
Quality Control ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Bacterial Protein ◽  
Allosteric Activation ◽  
Stress Signals

scholarly journals Heat-shock proteases promote survival of Pseudomonas aeruginosa during growth arrest

2020 ◽  
Vol 117 (8) ◽  
pp. 4358-4367 ◽  
Author(s):  
David W. Basta ◽  
David Angeles-Albores ◽  
Melanie A. Spero ◽  
John A. Ciemniecki ◽  
Dianne K. Newman
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cell Death ◽  
Heat Shock ◽  
Protein Aggregation ◽  
Protein Quality ◽  
Growth Arrest ◽  
Cellular Level ◽  
Secondary Response ◽  
Bacterial Cells ◽  
Encoding Genes

When nutrients in their environment are exhausted, bacterial cells become arrested for growth. During these periods, a primary challenge is maintaining cellular integrity with a reduced capacity for renewal or repair. Here, we show that the heat-shock protease FtsH is generally required for growth arrest survival of Pseudomonas aeruginosa, and that this requirement is independent of a role in regulating lipopolysaccharide synthesis, as has been suggested for Escherichia coli. We find that ftsH interacts with diverse genes during growth and overlaps functionally with the other heat-shock protease-encoding genes hslVU, lon, and clpXP to promote survival during growth arrest. Systematic deletion of the heat-shock protease-encoding genes reveals that the proteases function hierarchically during growth arrest, with FtsH and ClpXP having primary, nonredundant roles, and HslVU and Lon deploying a secondary response to aging stress. This hierarchy is partially conserved during growth at high temperature and alkaline pH, suggesting that heat, pH, and growth arrest effectively impose a similar type of proteostatic stress at the cellular level. In support of this inference, heat and growth arrest act synergistically to kill cells, and protein aggregation appears to occur more rapidly in protease mutants during growth arrest and correlates with the onset of cell death. Our findings suggest that protein aggregation is a major driver of aging and cell death during growth arrest, and that coordinated activity of the heat-shock response is required to ensure ongoing protein quality control in the absence of growth.

scholarly journals Why? – Successful Pseudomonas aeruginosa clones with a focus on clone C

2020 ◽  
Vol 44 (6) ◽  
pp. 740-762
Author(s):  
Changhan Lee ◽  
Jens Klockgether ◽  
Sebastian Fischer ◽  
Janja Trcek ◽  
Burkhard Tümmler ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Core Genome ◽  
Genomic Island ◽  
Protein Quality ◽  
Temperature Tolerance ◽  
Protein Homeostasis ◽  
Gene Products ◽  
Accessory Genome ◽  
The Core ◽  
Conserved Core

ABSTRACT The environmental species Pseudomonas aeruginosa thrives in a variety of habitats. Within the epidemic population structure of P. aeruginosa, occassionally highly successful clones that are equally capable to succeed in the environment and the human host arise. Framed by a highly conserved core genome, individual members of successful clones are characterized by a high variability in their accessory genome. The abundance of successful clones might be funded in specific features of the core genome or, although not mutually exclusive, in the variability of the accessory genome. In clone C, one of the most predominant clones, the plasmid pKLC102 and the PACGI-1 genomic island are two ubiquitous accessory genetic elements. The conserved transmissible locus of protein quality control (TLPQC) at the border of PACGI-1 is a unique horizontally transferred compository element, which codes predominantly for stress-related cargo gene products such as involved in protein homeostasis. As a hallmark, most TLPQC xenologues possess a core genome equivalent. With elevated temperature tolerance as a characteristic of clone C strains, the unique P. aeruginosa and clone C specific disaggregase ClpG is a major contributor to tolerance. As other successful clones, such as PA14, do not encode the TLPQC locus, ubiquitous denominators of success, if existing, need to be identified.

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