Comparative evaluation of structure and characteristic of peptidyl-prolyl cis-trans isomerase proteins and their function in Salmonella Typhimurium stress responses and virulence

Kumawat, Manoj; Singh, Piyush Kumar; Rananaware, Supriya Rajendra; Ahlawat, Sushma

doi:10.1007/s12223-019-00717-z

Cited by 7 publications

(5 citation statements)

References 48 publications

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“…Interestingly, in IPA analyses the endoplasmic reticulum stress pathway (z = 0.4, − log(p) = 5.23) and unfolded protein response (z = 0.3, − log(p) = 2.84) were slightly activated in the normoxic sCLU-transfected cells, suggesting the contribution of CLU to protein homeostasis in the hooded seal brain. In addition, the chaperone peptidylprolyl isomerase C (PPIC, log2FC = 1.15) was upregulated in sCLU cells, which may also be important for coping with oxidative stress [ 58 , 67 ]. Additionally, a utophagy (z = 0.2, − log(p) = 2.51), which promotes degradation of damaged proteins was slightly activated in the sCLU-transfected cell line.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to high expression of BNIP3 (log2FC = 1.36), HIF1-upregulated mitochondria-localized glutamic acid rich protein (MGARP, log2FC = 1.33) was highly expressed in sCLU cells and might further support mitophagy [ 43 ], which may reduce deleterious ROS by clearance of dysfunctional mitochondria. Additionally, upregulation of PPIC (log2FC = 2.06) may have further improved protein folding and reduced ER stress in the sCLU-transfected cell line [ 58 , 67 ]. According to described neurotrophic functions, intrinsic apoptotic signaling (FE = 3.6, p FDR < 0.05) as well as MYC mediated apoptosis (z = − 1.7, − log(p) = 1.6) were found to be downregulated in the sCLU cell line.…”

Section: Resultsmentioning

confidence: 99%

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Transcriptomes of Clusterin- and S100B-transfected neuronal cells elucidate protective mechanisms against hypoxia and oxidative stress in the hooded seal (Cystophora cristata) brain

et al. 2022

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Background The hooded seal (Cystophora cristata) exhibits impressive diving skills and can tolerate extended durations of asphyxia, hypoxia and oxidative stress, without suffering from irreversible neuronal damage. Thus, when exposed to hypoxia in vitro, neurons of fresh cortical and hippocampal tissue from hooded seals maintained their membrane potential 4–5 times longer than neurons of mice. We aimed to identify the molecular mechanisms underlying the intrinsic neuronal hypoxia tolerance. Previous comparative transcriptomics of the visual cortex have revealed that S100B and clusterin (apolipoprotein J), two stress proteins that are involved in neurological disorders characterized by hypoxic conditions, have a remarkably high expression in hooded seals compared to ferrets. When overexpressed in murine neuronal cells (HN33), S100B and clusterin had neuroprotective effects when cells were exposed to hypoxia. However, their specific roles in hypoxia have remained largely unknown. Methods In order to shed light on potential molecular pathways or interaction partners, we exposed HN33 cells transfected with either S100B, soluble clusterin (sCLU) or nuclear clusterin (nCLU) to normoxia, hypoxia and oxidative stress for 24 h. We then determined cell viability and compared the transcriptomes of transfected cells to control cells. Potential pathways and upstream regulators were identified via Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA). Results HN33 cells transfected with sCLU and S100B demonstrated improved glycolytic capacity and reduced aerobic respiration at normoxic conditions. Additionally, sCLU appeared to enhance pathways for cellular homeostasis to counteract stress-induced aggregation of proteins. S100B-transfected cells sustained lowered energy-intensive synaptic signaling. In response to hypoxia, hypoxia-inducible factor (HIF) pathways were considerably elevated in nCLU- and sCLU-transfected cells. In a previous study, S100B and sCLU decreased the amount of reactive oxygen species and lipid peroxidation in HN33 cells in response to oxidative stress, but in the present study, these functional effects were not mirrored in gene expression changes. Conclusions sCLU and S100B overexpression increased neuronal survival by decreasing aerobic metabolism and synaptic signaling in advance to hypoxia and oxidative stress conditions, possibly to reduce energy expenditure and the build-up of deleterious reactive oxygen species (ROS). Thus, a high expression of CLU isoforms and S100B is likely beneficial during hypoxic conditions.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Transcriptomes of Clusterin- and S100B-transfected neuronal cells elucidate protective mechanisms against hypoxia and oxidative stress in the hooded seal (Cystophora cristata) brain

et al. 2022

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“…In this study, we have characterized Cyclophilin A protein from Salmonella that showed high protein peptides sequence homology to CyPs from other organisms and demonstrated the PPIase activity of recombinant protein exhibited by arti cial enzyme substrate in vitro. Our previous work has reported cypA gene cloning and sequence from Salmonella Typhimurium showed that the cypA gene has high sequence similarity with other virulence bacteria (Manoj et al 2016;Kumawat et al 2020). Another study showed that ppiA, the gene that is highly conserved among all Salmonellagenomes, is a critical role in the growth of Salmonella Typhimurium in the examined stress conditions, and may play a role in its responses and virulence (Kumawat et al 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Our previous work has reported cypA gene cloning and sequence from Salmonella Typhimurium showed that the cypA gene has high sequence similarity with other virulence bacteria (Manoj et al 2016;Kumawat et al 2020). Another study showed that ppiA, the gene that is highly conserved among all Salmonellagenomes, is a critical role in the growth of Salmonella Typhimurium in the examined stress conditions, and may play a role in its responses and virulence (Kumawat et al 2020). Thus, this study will help to understand the importance of cyclophilin protein in Salmonella Typhimurium which may play various biological activities.…”

Section: Discussionmentioning

confidence: 99%

Purification and characterization of Cyclophilin: a protein associated with protein folding in Salmonella Typhimurium

Kumawat

Chaudhary²,

Nabi

et al. 2021

Arch Microbiol

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Salmonella Typhimurium (ST) is the zoonotic pathogenic Gram-negative bacteria to causes infectious disease in humans as well as in animals. It causes gastrointestinal illness and fever called salmonellosis, which is foodborne diarrheal and leading cause of millions of deaths worldwide. Salmonella enterica serovar Typhimurium (S. Typhimurium) during its pathogenesis takeaway the actin cytoskeleton of their host cells and this is the crucial step of its infection cycle. Cyclophilin A, a type of peptidyl-prolyl isomerase that's encoded by the ppiA gene in ST, plays pleiotropic roles in maintaining bacterial physiology. In this research, the proteomic characterization of the peptidyl-prolyl cis-trans isomerase-A (Cyclophilin A) from Salmonella Typhimurium is reported. Cyclophilin A (CypA) protein from Salmonella Typhimurium proved to be a highly conserved protein sequence and highly homologous compared to other organisms. This protein was expressed in Escherichia coli and then puri ed in a recombinant form protein exhibited a characteristic PPIases activity (V max = 0.8752 ± 0.13892 µmoles/ min, K m = 0.9315 ± 0.5670 µM) in comparison to control. Also, in this study the mass spectrometry analysis of Cyp A proteinpeptide showed the highest sequence similarity with the cyclophilin protein of Salmonella. PPIases proteins enzyme data suggest that Ppi-A has roles in the protein folding that may be contributing to the virulence of Salmonella by isomerization of protein outline. These results suggest an active and vital role of this protein in protein folding along with regulation in Salmonella Typhimurium.

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“…In agreement with this, microbial Cyps have been described to improve microbial survival under stress conditions and to be upregulated upon host-cell internalization, suggesting a possible function of these proteins in microbial-host interaction ( Dimou et al, 2017 ). Interestingly, the critical role of PPIases in stress tolerance and pathogenesis of bacteria has been demonstrated in Yersinia pseudotuberculosis ( Obi et al, 2011 ), Streptococcus pneumoniae ( Hermans et al, 2006 ), Enterococcus faecalis ( Reffuveille et al, 2012 ), Streptococcus gordoni ( Cho et al, 2013 ), Mycobacterium tuberculosis ( Pandey et al, 2017 ), Staphylococcus aureus ( Wiemels et al, 2017 ; Keogh et al, 2018 ), Legionella pneumophila ( Rasch et al, 2019 ), Burkholderia pseudomallei ( Bzdyl et al, 2019 ), and Salmonella Typhimurium ( Kumawat et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Biochemical and functional characterization of Brucella abortus cyclophilins: So similar, yet so different

Muruaga

Briones²,

Roset³

2022

Front. Microbiol.

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Brucella spp. are the etiological agent of animal and human brucellosis. We have reported previously that cyclophilins of Brucella (CypA and CypB) are upregulated within the intraphagosomal replicative niche and required for stress adaptation and host intracellular survival and virulence. Here, we characterize B. abortus cyclophilins, CypA, and CypB from a biochemical standpoint by studying their PPIase activity, chaperone activity, and oligomer formation. Even though CypA and CypB are very similar in sequence and share identical chaperone and PPIase activities, we were able to identify outstanding differential features between them. A series of differential peptide loops were predicted when comparing CypA and CypB, differences that might explain why specific antibodies (anti-CypA or anti-CypB) were able to discriminate between both cyclophilins without cross-reactivity. In addition, we identified the presence of critical amino acids in CypB, such as the Trp134 which is responsible for the cyclosporin A inhibition, and the Cys128 that leads to CypB homodimer formation by establishing a disulfide bond. Here, we demonstrated that CypB dimer formation was fully required for stress adaptation, survival within HeLa cells, and mouse infection in B. abortus. The presence of Trp134 and the Cys128 in CypB, which are not present in CypA, suggested that two different kinds of cyclophilins have evolved in Brucella, one with eukaryotic features (CypB), another (CypA) with similar features to Gram-negative cyclophilins.

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Comparative evaluation of structure and characteristic of peptidyl-prolyl cis-trans isomerase proteins and their function in Salmonella Typhimurium stress responses and virulence

Cited by 7 publications

References 48 publications

Transcriptomes of Clusterin- and S100B-transfected neuronal cells elucidate protective mechanisms against hypoxia and oxidative stress in the hooded seal (Cystophora cristata) brain

Transcriptomes of Clusterin- and S100B-transfected neuronal cells elucidate protective mechanisms against hypoxia and oxidative stress in the hooded seal (Cystophora cristata) brain

Purification and characterization of Cyclophilin: a protein associated with protein folding in Salmonella Typhimurium

Biochemical and functional characterization of Brucella abortus cyclophilins: So similar, yet so different

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