Research Articles
Clonal spread and environmental persistence of carbapenem-resistant high-risk Pseudomonas aeruginosa in critical-care units of a Chilean national referral center for burn and trauma patients (2022)
Camila Ibarra1, Gustavo Araya2, Alhejandra Alvarez2, Leonardo Enríquez2, Carolina Arellano2, Fabricio Alarcón1, Constanza Fernández1, Claudio Vargas1, Rodrigo Vera1 and Roberto M. Vidal2
This study highlight the circulation of high-risk P. aeruginosa clones in Chile and underscore the importance of molecular epidemiology in guiding infection control, optimizing antimicrobial therapy, and mitigating the clinical and economic burden of CRPA.
The transcriptome of dendritic cells redraws the boundaries between pathogenicity and commensalism in yeast
Lisa Rizzetto1, Irene Stefanini2, Stefano Nenciarini3, Monica Di Paola3, Samantha Riccadonna1, Ivo G. Gut4,5, Marta Gut4,5, Simon Heath4,5 and Duccio Cavalieri3
Our immune system meets many fungi, but reacts strongly to only a few. The comparison of key fungal species showed that responses differ mainly in timing and not just genes, highlighting the need to rethink what makes fungi harmful vs. harmless.
Yippee-like protein Moh1 links gene expression to metabolism and selective stress resistance in Saccharomyces cerevisiae
Çağla Ece Olgun1,a, Gizem Turan Duman1,a, Gizem Güpür1, Hamit İzgi1, Mariam Huda2, Demet Çetin3, Zekiye Suludere4, Fatma Küçük Baloğlu5, Ayşe Koca Çaydaşı2 and Mesut Muyan1
This study demonstrates that the conserved yeast protein Moh1 links metabolism, gene expression, and cell structure, thereby altering cell envelope permeability and leading to selective stress responses.
Fungistatic effect of sorbic acid on yeast cells via translational repression involving eIF2α phosphorylation and formation of Ded1- and eIF2B-granules
Haruka Yoshiyama1, Wataru Nomura2 and Shingo Izawa1
The findings of this study provide new insights into the physiological effects of sorbic acid on yeast cells, specifically regarding the regulation of translation-related factors.
Occlusal types shape oral microbiome stomatotypes and metabolic landscapes: A multi-omics perspective on host-microbe interaction
Yufeng Duan1,a, Zheng Liu2,3,a, Wenting Lu1,a, Ning Zhao1, Lingjun Yuan1, Zhenxia Li1, Ting Zhou1, Shengzhao Xiao1, Dian Jing1, Xiaowen Zheng1, Wentao Shi4, Chao Liu1,*, Haixia Lu5,*, Qiang Feng6,* and Bing Fang1,*
This study reveals how occlusal types shape oral microbiome “stomatotypes” and metabolic profiles in adolescents. It offers fresh insights that host anatomy drives microecology which may be associated with personalized oral health.
Genomic epidemiology of carbapenemase-producing Klebsiella pneumoniae circulating in a Chilean tertiary-care hospital (2021–2022): Molecular characterization, resistance-virulence convergence, and clinical associations
Gustavo Araya1,2, Alhejandra Álvarez1, Carolina Arellano1, Rodrigo Bravo3, Abraham Gajardo4,5, Boris Barrera6, Francisco Silva6 and Roberto M. Vidal1
This study characterized carbapenem-resistant Kp (CR-Kp) strains isolated at the Hospital Clínico Universidad de Chile (HCUCH) 2021-2022 and explored associations with clinical characteristics.
Sugar-induced cell death (SICD) in Saccharomyces cerevisiae: insights into nitrogen-mediated rescue and apoptotic cell death pathways
Raveena Parbhudayal and Hai-Ping Cheng
This study examined mechanisms through which yeast sugar-induced cell death can be prevented. High concentrations of glucose induced a catastrophic response that was only rescued by highly preferred nitrogen sources and by preventing nuclear localization of specific cell death proteins.
TOR-dependent regulation of the yeast homolog of the juvenile Batten Disease-associated gene CLN3
Vijaykumar Pillalamarri1, Samuel W.M. Gatesy1, Amanda E. Grassel1, Lucienna Wolf1, Justin P. Whalley2 and David M. Mueller1,*
This study identifies conditions and genes that induce BTN1 expression in yeast. We show that BTN1 expression is regulated by translational control and by the mTOR1 pathway. An understanding of when and why BTN1 expression will aid in understanding the expression of CLN3, which may be helpful in the treatment of this devastating disease.
Metagenomic and microbiological analyses of historical manuscripts for bacterial community profiling and bacteria-related biodeterioration assessment
Esra Keles1,* and Ozge Celik2
By documenting both culturable and non-culturable taxa, this work provides a foundational dataset for understanding bacterial contributions to manuscript stability and offers a methodological framework for future research on biodeterioration dynamics in Islamic and global documentary heritage.
The lysosomotropic drug LeuLeu-OMe induces lysosome disruption and autophagy-independent cell death in Trypanosoma brucei
July 30, 2015
Trypanosoma brucei is a blood-borne, protozoan parasite that causes African sleeping sickness in humans and nagana in animals. The current chemotherapy relies on only a handful of drugs that display undesirable toxicity, poor efficacy and drug-resistance. In this study, we explored the use of lysosomotropic drugs to induce bloodstream form T. brucei cell death via lysosome destabilization. We measured drug concentrations that inhibit cell proliferation by 50% (IC50) for several compounds, chosen based on their lysosomotropic effects previously reported in Plasmodium falciparum. The lysosomal effects and cell death induced by L-leucyl-L-leucyl methyl ester (LeuLeu-OMe) were further analyzed by flow cytometry and immunofluorescence analyses of different lysosomal markers...
In Entamoeba histolytica, a BspA family protein is required for chemotaxis toward tumour necrosis factor
July 6, 2015
Background: Entamoeba histolytica cell migration is essential for the development of human amoebiasis (an infectious disease characterized by tissue invasion and destruction). The tissue inflammation associated with tumour necrosis factor (TNF) secretion by host cells is a well-documented feature of amoebiasis. Tumour necrosis factor is a chemoattractant for E. histolytica, and the parasite may have a TNF receptor at its cell surface. Methods: confocal microscopy, RNA Sequencing, bioinformatics, RNA antisense techniques and histological analysis of human colon explants were used to characterize the interplay between TNF and E. histolytica. Results: an antibody against human TNF receptor 1 (TNFR1) stained the E. histolytica trophozoite...
Polyamines directly promote antizyme-mediated degradation of ornithine decarboxylase by the proteasome
May 20, 2015
Ornithine decarboxylase (ODC), a ubiquitin-independent substrate of the proteasome, is a homodimeric protein with a rate-limiting function in polyamine biosynthesis. Polyamines regulate ODC levels by a feedback mechanism mediated by ODC antizyme (OAZ). Higher cellular polyamine levels trigger the synthesis of OAZ and also inhibit its ubiquitin-dependent proteasomal degradation. OAZ binds ODC monomers and targets them to the proteasome. Here, we report that polyamines, aside from their role in the control of OAZ synthesis and stability, directly enhance OAZ-mediated ODC degradation by the proteasome. Using a stable mutant of OAZ, we show that polyamines promote ODC degradation in Saccharomyces cerevisiae cells even when OAZ levels are not changed. Furthermore, polyamines stimulated the in vitro degradation of ODC by the...
Toxoplasma gondii inhibits cytochrome c-induced caspase activation in its host cell by interference with holo-apoptosome assembly
May 4, 2015
Inhibition of programmed cell death pathways of mammalian cells often facilitates the sustained survival of intracellular microorganisms. The apicomplexan parasite Toxoplasma gondii is a master regulator of host cell apoptotic pathways. Here, we have characterized a novel anti-apoptotic activity of T. gondii. Using a cell-free cytosolic extract model, we show that T. gondii interferes with the activities of caspase 9 and caspase 3/7 which have been induced by exogenous cytochrome c and dATP. Proteolytic cleavage of caspases 9 and 3 is also diminished suggesting inhibition of holo-apoptosome function. Parasite infection of Jurkat T cells and subsequent triggering of apoptosome formation by exogenous cytochrome c in vitro and in vivo indicated that...
Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism
April 6, 2015
Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA), namely PKAN and CoPAN. Yeast expressing a pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.
Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites
January 4, 2015
Horizontal gene transfer has emerged as a crucial driving force for the evolution of eukaryotes. This also includes Plasmodium falciparum and related economically and clinically relevant apicomplexan parasites, whose rather small genomes have been shaped not only by natural selection in different host populations but also by horizontal gene transfer following endosymbiosis. However, there is rather little reliable data on horizontal gene transfer between animal hosts or bacteria and apicomplexan parasites. Here we show that apicomplexan homologues of peroxiredoxin 5 (Prx5) have a prokaryotic ancestry and therefore represent a special subclass of Prx5 isoforms in eukaryotes. Using two different immunobiochemical approaches, we found that...
Two distinct and competitive pathways confer the cellcidal actions of artemisinins
January 1, 2015
The biological actions of artemisinin (ART), an antimalarial drug derived from Artemisia annua, remain poorly understood and controversial. This article concludes that ARTs are endowed with two major and distinct types of properties: a potent and specific mitochondria-dependent reaction and a more general and less specific heme-mediated reaction. The competitive nature of these two actions could be explained by their shared source of the consumable ARTs, so that inhibition of the heme-mediated degradation pathway would enable more ARTs to be available for the mitochondrial action. These properties of ARTs can be used to interpret the divergent antimalarial and anticancer actions of ARTs.
Measurement of apoptosis by SCAN©, a system for counting and analysis of fluorescently labelled nuclei
November 26, 2014
This work reports on a system for analyses of apoptosis-like programmed cell death in fungal hyphae that is composed of several modules, which enable automatic quantification of nuclei with chromatin condensation and DNA strand break in large datasets according to nuclei-associated fluorescent markers.
Rewiring yeast acetate metabolism through MPC1 loss of function leads to mitochondrial damage and decreases chronological lifespan
November 18, 2014
This work shows that MPC1-deficient cells make up for their impairment in mitochondrial pyruvate with a metabolic rewiring which involves several intermediates of the mitochondrially localized TCA cycle and the cytosolic glyoxylate shunt but ultimately results in a pro-aging process.