Review, Reviews
Infinity war: Trichomonas vaginalis and interactions with host immune response
Giulia Bongiorni Galego1 and Tiana Tasca1
Trichomonas vaginalis is the pathological agent of human trichomoniasis with an incidence of 156 million cases worldwide. This review highlights parasite strategies to activate and stimulate or evade variated and complex immunological mechanisms related to the symptoms and clinical complications observed here.
The metabolites of lactic acid bacteria: classification, biosynthesis and modulation of gut microbiota
Huang Tang1,2, Wanqiu Huang1,2 and Yu-Feng Yao1,2,3,4,5
Lactic acid bacteria (LAB) are ubiquitous microorganisms that can colonize the intestine and participate in the physiological metabolism of the host. In this review, we summarize the metabolites of LAB and their influence on the intestine as well as the underlying regulatory mechanisms and their impact on human health.
Effects of the intestinal microbiota on prostate cancer treatment by androgen deprivation therapy
Safae Terrisse1, Laurence Zitvogel2-5 and Guido Kroemer6-8
Prostate cancer (PC) can be kept in check by androgen deprivation therapy (ADT, usually with the androgen synthesis inhibitor abiraterone acetate or the androgen receptor antagonist such as enzalutamide) until the tumor evolves to castration-resistant prostate cancer (CRPC). The transition of hormone-sensitive PC (HSPC) to CPRC has been explained by cancer cell-intrinsic resistance mechanisms. Recent data indicate that this transition is also marked by cancer cell-extrinsic mechanisms such as the failure of ADT-induced PC immunosurveillance, which depends on the presence of immunostimulatory bacteria in the gut. Moreover, intestinal bacteria that degrade drugs used for ADT, as well as bacteria that produce androgens, can interfere with the efficacy of ADT. Thus, specific bacteria in the gut serve as a source of testosterone, which accelerates prostate cancer progression, and men with CRPC exhibit an increased abundance of such bacteria with androgenic functions. In conclusion, the response of PC to ADT is profoundly influenced by the composition of the microbiota with its immunostimulatory, immunosuppressive and directly ADT-subversive elements.
Occurrence and potential mechanism of holin-mediated non-lytic protein translocation in bacteria
Thomas Brüser1 and Denise Mehner-Breitfeld1
Holins are generally believed to generate large membrane lesions that permit the passage of endolysins across the cytoplasmic membrane of prokaryotes, ultimately resulting in cell wall degradation and cell lysis. However, there are more and more examples known for non-lytic holin-dependent secretion of proteins by bacteria, indicating that holins somehow can transport proteins without causing large membrane lesions. Phage-derived holins can be used for a non-lytic endolysin translocation to permeabilize the cell wall for the passage of secreted proteins. In addition, clostridia, which do not possess the Tat pathway for transport of folded proteins, most likely employ non-lytic holin-mediated transport also for secretion of toxins and bacteriocins that are incompatible with the general Sec pathway. The mechanism for non-lytic holin-mediated transport is (...)
Swimming faster despite obstacles: a universal mechanism behind bacterial speed enhancement in complex fluids
Bacteria constitute about 15% of global biomass and their natural environments often contain polymers and colloids, which show complex flow properties. It is crucial to study their motion in such environments to understand their growth and spreading as well as to design synthetic microswimmers for biomedical applications. Bacterial motion in complex viscous environments, although extensively studied over the past six decades, still remains poorly understood. In our recent study combining experimental data and theoretical analysis, we found a surprising similarity between bacterial motion in dilute colloidal suspensions and polymer solutions, which challenged the established view on the role of polymer dynamics on bacterial speed enhancement. We subsequently developed a physical model that provides a universal mechanism explaining bacterial speed enhancement (...)
A roadmap for designing narrow-spectrum antibiotics targeting bacterial pathogens
Xinyun Cao1,*, Robert Landick1,2, Elizabeth A. Campbell3
This comment discusses the article "Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile" by Cao et al. (2022, Nature).
Breaking the clip for cargo unloading from motor proteins: mechanism and significance
Keisuke Obara1, and Takumi Kamura1
The mitochondrion is an essential organelle involved in ATP generation, lipid metabolism, regulation of calcium ions, etc. Therefore, it should be inherited properly by newly generated cells. In the budding yeast Saccharomyces cerevisiae, mitochondria are passed on to daughter cells by the motor protein, Myo2, on the actin cable. The mitochondria and Myo2 are connected via the adaptor protein Mmr1. After reaching daughter cells, mitochondria are released from the actin-myosin machinery and move dynamically. In our recent paper (Obara K et al. (2022), Nat Commun, doi:10.1038/s41467-022-29704-8), we demonstrated that the regulated proteolysis of Mmr1 is required for the unloading of mitochondria from Myo2 in daughter cells. Sequential post-translational modifications of Mmr1, i.e., phosphorylation followed by ubiquitination, are essential for Mmr1 degradation and mitochondrial release from Myo2. Defects in Mmr1 degradation cause stacking and deformation of mitochondria at the bud-tip and bud-neck, where Myo2 accumulates. Compared to wild-type cells, mutant cells with defects in Mmr1 degradation possess an elevated mitochondrial membrane potential and produce higher levels of reactive oxygen species (ROS), along with hypersensitivity to oxidative stress.
Pirates of the haemoglobin
Daniel Akinbosede1, Robert Chizea1 and Stephen A. Hare1,†
Not all treasure is silver and gold; for pathogenic bacteria, iron is the most precious and the most pillaged of metallic elements. Iron is essential for the survival and growth of all life; however free iron is scarce for bacteria inside human hosts. As a mechanism of defence, humans have evolved ways to store iron so as to render it inaccessible for invading pathogens, such as keeping the metal bound to iron-carrying proteins. For bacteria to survive within humans, they must therefore evolve counters to this defence to compete with these proteins for iron binding, or directly steal iron from them. (...)
The integrated stress response in budding yeast lifespan extension
October 24, 2017
This article summarizes how the budding yeast Saccharomyces cerevisiae has been instrumental in unraveling the molecular and cellular determinants of aging, and how the induction of cellular stress responses has been associated with experimental lifespan extension, thus underscoring the value of yeast as a model for developing potential aging therapies for humans.
Macrophages as drivers of an opportunistic infection
September 13, 2017
This article comments on work published by Mesureur et al. (PloS Pathog, 2017), which shows that macrophages are essential for proliferation of B. cenocepacia in the host. This suggests a new paradigm for Bcc infections and urges the development of novel anti-infectious therapies to efficiently disarm these intrinsically antibiotic resistant facultative intracellular pathogens.
Exacerbating and reversing lysosomal storage diseases: from yeast to humans
August 25, 2017
This article summarizes the use of yeast models in advancing our understanding of lysosomal storage diseases (LSDs), where they have been instrumental in researching LSD mechanisms, screening for therapeutic compounds, and exploring genetic and gene-environment interactions relevant to diseases like Batten disease, cystinosis, and Niemann-Pick type C disease, as well as their connection to broader health issues such as viral infections and obesity.
Live fast, die fast principle in a single cell of fission yeast
August 13, 2017
This article comments on a recent study (Nakaoka and Wakamoto, PLoS Biol, 2017), which developed a microfluidics-based platform to track multiple single cell lineages until death.
Out with the old: Hsp90 finds amino acid residue more useful than co-chaperone protein
August 1, 2017
This article comments on work published by Zuehlke et al (Nat Commun, 2017), which demonstrates that the function of one co-chaperone in yeast is replaced by posttranslational modification (PTM) of a single amino acid within Hsp90 in higher eukaryotes.
Having your cake and eating it – Staphylococcus aureus small colony variants can evolve faster growth rate without losing their antibiotic resistance
August 1, 2017
This article comments on work published by Cao et al. (mBio, 2027), which shows that Staphylococcus aureus can produce small colony variants (SCVs) that are challenging to detect and lead to persistent infections due to mutations affecting respiration and ATP production, with recent findings indicating various evolutionary paths for SCVs to increase growth rate while maintaining antibiotic resistance, suggesting greater adaptability and clinical challenge.
The interplay between transcription and mRNA degradation in Saccharomyces cerevisiae
July 3, 2017
This review summarizes how the integration of mRNA synthesis and degradation, mediated by specialized promoters and "coordinators," shapes the cellular transcriptome and plays a significant role in regulating gene expression profiles in various biological processes and potentially enhances evolutionary rates.