Research Articles
Predictable regulation of survival by intratumoral microbe-immune crosstalk in patients with lung adenocarcinoma
Shuo Shi1, Yuwen Chu2,3, Haiyan Liu4,5, Lan Yu6,7,8, Dejun Sun8,9, Jialiang Yang2,3,5, Geng Tian2,3, Lei Ji2,3, Cong Zhang10 and Xinxin Lu11
Intratumoral microbiota can regulate the tumor immune microenvironment (TIME) and mediate tumor prognosis by promoting inflammatory response or inhibiting anti-tumor effects. Our study demonstrated that intratumoral microbiota-immune crosstalk was strongly associated with prognosis in LUAD patients, which would provide new targets for the development of precise therapeutic strategies.
The last two transmembrane helices in the APC-type FurE transporter act as an intramolecular chaperone essential for concentrative ER-exit
Yiannis Pyrris1, Georgia F. Papadaki1, Emmanuel Mikros2 and George Diallinas1,3
FurE is a H+ symporter specific for the cellular uptake of uric acid, allantoin, uracil, and toxic nucleobase analogues in the fungus Aspergillus nidulans. Being member of the NCS1 protein family, FurE is structurally related to the APC-superfamily of transporters.
Basal level of ppGpp coordinates Escherichia coli cell heterogeneity and ampicillin resistance and persistence
Paulina Katarzyna Grucela1 and Yong Everett Zhang1
The universal stringent response alarmone ppGpp (guanosine penta and tetra phosphates) plays a crucial role in various aspects of fundamental cell physiology (e.g., cell growth rate, cell size) and thus bacterial tolerance to and survival of external stresses, including antibiotics. In tihs study, we discuss the fundamental role of basal level of ppGpp in regulating cell homogeneity and ampicillin persistence.
Investigation of the acetic acid stress response in Saccharomyces cerevisiae with mutated H3 residues
Nitu Saha1, Swati Swagatika1 and Raghuvir Singh Tomar1
Yeast cells respond to acetic acid in diverse ways. Here, we have elucidated the deleterious effects of acetic acid on different histone mutants
The coenzyme B12 precursor 5,6-dimethylbenzimidazole is a flavin antagonist in Salmonella
Lahiru Malalasekara1 and Jorge C. Escalante-Semerena1,*
Here we investigated why 5,6-dimethylbenzimidazole (DMB) inhibits in S. Typhimurium. Briefly, we determined that the structural similarities of the substituted benzene ring of DMB with the isoalloxazine moiety of flavins is responsible for the deleterious effects of this CoB12 precursor.
GFP fusions of Sec-routed extracellular proteins in Staphylococcus aureus reveal surface-associated coagulase in biofilms
Dominique C. S. Evans1,2,#, Amanda B. Khamas1,#, Lisbeth Marcussen1, Kristian S. Rasmussen3, Janne K. Klitgaard3, Birgitte H. Kallipolitis3, Janni Nielsen1, Daniel E. Otzen1, Mark C. Leake2,4 and Rikke L. Meyer1,5
We show that msfGFP can be used to generate extracellular fluorescent fusion proteins in S. aureus, applicable for proteins that are secreted through the Sec pathway. When fused to coagulase, msfGFP did not hinder the biological function, and the fusion protein localised to the fibrin pseudocapsule surrounding clusters of S. aureus cells.
DadY (PA5303) is required for fitness of Pseudomonas aeruginosa when growth is dependent on alanine catabolism
November 22, 2022
Pseudomonas aeruginosa inhabits diverse environmental niches that can have varying nutrient composition. The ubiquity of this organism is facilitated by a metabolic strategy that preferentially utilizes low-energy, non-fermentable organic acids, such as amino acids, rather than the high-energy sugars preferred by many other microbes. The amino acid alanine is among the preferred substrates of P. aeruginosa. The dad locus encodes the constituents of the alanine catabolic pathway of P. aeruginosa. Physiological roles for DadR (AsnC-type transcriptional activator), DadX (alanine racemase), and DadA (D-amino acid dehydrogenase) have been defined in this pathway. An additional protein, PA5303, is encoded in the dad locus in P. aeruginosa. PA5303 is a member of the ubiquitous Rid protein superfamily and is designated DadY based on the data presented herein. (...)
Multiple genome analysis of Candida glabrata clinical isolates renders new insights into genetic diversity and drug resistance determinants
October 13, 2022
The emergence of drug resistance significantly hampers the treatment of human infections, including those caused by fungal pathogens such as Candida species. Candida glabrata ranks as the second most common cause of candidiasis worldwide, supported by rapid acquisition of resistance to azole and echinocandin antifungals frequently prompted by single nucleotide polymorphisms (SNPs) in resistance associated genes, such as PDR1 (azole resistance) or FKS1/2 (echinocandin resistance). To determine the frequency of polymorphisms and genome rearrangements as the possible genetic basis of C. glabrata drug resistance, we assessed genomic variation across 94 globally distributed isolates with distinct resistance phenotypes, whose sequence is deposited in GenBank. The(...)
Up-regulation of Osh6 boosts an anti-aging membrane trafficking pathway toward vacuoles
July 15, 2022
Members of the family of oxysterol-binding proteins mediate non-vesicular lipid transport between membranes and contribute to longevity in different manners. We previously found that a 2-fold up-regulation of Osh6, one of seven yeast oxysterol-binding proteins, remedies vacuolar morphology defects in mid-aged cells, partly down-regulates the target of rapamycin complex 1 (TORC1), and increases the replicative lifespan. At the molecular level, Osh6 transports phosphatidylserine (PS) and phosphatidylinositol-4-phosphate (PI4P) between the endoplasmic reticulum (ER) and the plasma membrane (PM). To decipher how an ER-PM working protein controls vacuolar morphology, we tested genetic interactions between OSH6 and DRS2, whose protein flips PS from the lumen to the cytosolic side of the Golgi, the organelle between ER and vacuoles in many pathways. Up-regulated (...)
Investigating the role of G-quadruplexes at Saccharomyces cerevisiae telomeres
May 19, 2022
In this study, the authors examine the in vivo relevance of telomeric G-quadruplexes in the budding yeast Saccharomyces cerevisiae by expressing a mutant telomerase RNA subunit (tlc1-tm) that introduces mutant telomeric repeats instead to the distal ends of telomeres. (...)
Air- and dustborne fungi in repositories of the National Archive of the Republic of Cuba
April 1, 2022
This study has as objectives to determine the concentration and diversity of the air- and dustborne mycobiota in seven National Archive of the Republic of Cuba repositories, and to assess the potential risk of biodeterioration that iso-lated taxa may have. In the indoor and outdoor environmental microbiological samplings a SAS biocollector was used and the indoor/outdoor (I/O) ratio was determined for each repository. The settled dust was collected during six months. Sørensen's coefficient of similarity (QS) was calculated to compare the isolated taxa among the three studied niches (indoor air, dust, outdoor air). The biodegradation potential of the isolated taxa was determined by semi-quantitative tests. The concentrations in the air of repositories with natural cross-ventilation ranged from 225.2-750.3 CFU m-3, while in the Map library with air-conditioning (...)
Cleavage-defective Topoisomerase I mutants sharply increase G-quadruplex-associated genomic instability
January 31, 2022
Topoisomerase 1 (Top1) removes transcription-associated helical stress to suppress G4-formation and its induced recombination at genomic loci containing guanine-run containing sequences. Interestingly, Top1 binds tightly to G4 structures, and its inhibition or depletion can cause elevated instability at these genomic loci. Top1 is targeted by the widely used anti-cancer chemotherapeutic camptothecin (CPT) and its derivatives, which stabilize Top1 covalently attached on a DNA nick and prevent the re-ligation step. Here we investigated how CPT-resistance conferring Top1 mutants, which emerge in cancer patients and cells treated with CPT, affect G4-induced genomic instability in S. cerevisiae. We found that Top1 mutants form stable complexes with G4 DNA and that expression of Top1 cleavage-defective mutants but not a DNA-binding-defective (...)
Chromosome-condensed G1 phase yeast cells are tolerant to desiccation stress
November 26, 2021
The budding yeast Saccharomyces cerevisiae is capable of surviving extreme water loss for a long time. However, less is known about the mechanism of its desiccation tolerance. In this study, we revealed that in an exponential culture, all desiccation tolerant yeast cells were in G1 phase and had condensed chromosomes. (...)
Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its first variants in fourplex real-time quantitative reverse transcription-PCR assays
November 25, 2021
The early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is required to identify and isolate contagious patients to prevent further transmission of SARS-CoV-2. In this study, we present a multitarget real-time TaqMan reverse transcription PCR (rRT-PCR) assay for the quantitative detection of SARS-CoV-2 and some of its circulating variants harboring mutations that give the virus a selective advantage. Seven different primer-probe sets that included probes containing locked nucleic acid (LNA) nucleotides were designed to amplify specific wild-type and mutant sequences in Orf1ab, Envelope (E), Spike (S), and Nucleocapsid (N) genes (...)
Forced association of SARS-CoV-2 proteins with the yeast proteome perturb vesicle trafficking
October 27, 2021
This work demonstrates that the yeast Synthetic Physical Interactions method is a rapid way to identify potential functions of ectopic viral proteins.
Airborne bacteria in show caves from Southern Spain
July 26, 2021
This study analyzes the factors conditioning the diversity of airborne bacteria recorded in three Andalusian show caves, subjected to different managements.