Review, Reviews
A global view of substrate phosphorylation and dephosphorylation during budding yeast mitotic exit
Sandra A. Touati1 and Frank Uhlmann1
In this article, the authors comment on the study "Phosphoproteome dynamics during mitotic exit in budding yeast" by Touati (EMBO J, 2018) that described a time-resolved global phosphoproteome analysis during a cell cycle phase known as mitotic exit in budding yeast revealed the principles of phosphoregulation governing the ordered sequence of events such as spindle elongation, chromosome decondensation, and completion of cell division.
Gammaretroviruses tether to mitotic chromatin by directly binding nucleosomal histone proteins
Madushi Wanaguru1 and Kate N. Bishop1
In this article, the authors comment on the study "Murine leukemia virus p12 tethers the capsid-containing pre-integration complex to chromatin by binding directly to host nucleosomes in mitosis" by Wanaguruet al. (PLoS Pathog, 2018) that highlights the essential role of the gammaretroviral gag cleavage product, p12, at both early and late stages of the virus life cycle, particularly in the integration of the viral DNA into the host cell chromatin to form a provirus. It also emphasizes the recent findings regarding the N- and C-terminal domains of p12, revealing their direct binding to the viral capsid lattice and nucleosomal histone proteins, respectively, thus elucidating the mechanism by which p12 links the viral pre-integration complex to mitotic chromatin.
Methodologies for in vitro and in vivo evaluation of efficacy of antifungal and antibiofilm agents and surface coatings against fungal biofilms
Patrick Van Dijck1,2,‡, Jelmer Sjollema3,‡, Bruno P.A. Cammue4,5, Katrien Lagrou6,7, Judith Berman8, Christophe d’Enfert9, David R. Andes10,11, Maiken C. Arendrup12-14, Axel A. Brakhage15, Richard Calderone16, Emilia Cantón17, Tom Coenye18,19, Paul Cos20, Leah E. Cowen21, Mira Edgerton22, Ana Espinel-Ingroff23, Scott G. Filler24, Mahmoud Ghannoum25, Neil A.R. Gow26, Hubertus Haas27, Mary Ann Jabra-Rizk28, Elizabeth M. Johnson29, Shawn R. Lockhart30, Jose L. Lopez-Ribot31, Johan Maertens32, Carol A. Munro26, Jeniel E. Nett33, Clarissa J. Nobile34, Michael A. Pfaller35,36, Gordon Ramage19,37, Dominique Sanglard38, Maurizio Sanguinetti39, Isabel Spriet40, Paul E. Verweij41, Adilia Warris42, Joost Wauters43, Michael R. Yeaman44, Sebastian A.J. Zaat45, Karin Thevissen4,*
This article highlights the critical importance of accurate susceptibility testing methods and the discovery of novel antifungal and antibiofilm agents in combating invasive fungal infections associated with biofilm formation on medical devices, thereby emphasizing the need for advancements in medical mycology research to address these complex diseases.
Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks
Gabriele A. Fontana1, Julia K. Reinert1,2, Nicolas H. Thomä1, Ulrich Rass1
This review discusses the conserved mechanisms cells have evolved to protect DNA ends at chromosomal termini and DNA double-strand breaks (DSBs), focusing on the protein Rif1’s roles in telomere homeostasis and DSB repair in eukaryotes. It highlights the intriguing connection between Rif1's involvement in both telomere maintenance and DSB repair, and suggests that excluding end-processing factors may underlie Rif1's diverse biological functions at telomeres and chromosome breaks.
The CRISPR conundrum: evolve and maybe die, or survive and risk stagnation
Jesús García-Martínez1, Rafael D. Maldonado1, Noemí M. Guzmán1 and Francisco J. M. Mojica1,2
In this article García-Martínez et al. cover how the model bacterium Escherichia coli deals with CRISPR-Cas to tackle the major dilemma of evolution versus survival.
Metabolic disharmony and sibling conflict mediated by T6SS
Vera Troselj1 and Daniel Wall1
In this article, the authors comment on the study "Physiological Heterogeneity Triggers Sibling Conflict Mediated by the Type VI Secretion System in an Aggregative Multicellular Bacterium" by Troselj et al. (MBio, 2018) discussing that M. xanthus uses T6SS to eliminate less fit cells from their population and identified toxic effector and cognate immunity protein (TsxEI) that mediates this sibling antagonism.
Helicobacter hepaticus polysaccharide induces an anti-inflammatory response in intestinal macrophages
Camille Danne1 and Fiona Powrie1
In this article, the authors comment on the study "A Large Polysaccharide Produced by Helicobacter hepaticus Induces an Anti-inflammatory Gene Signature in Macrophages. " by Danne et al, (Cell Host Microbe 2017), discussing the interactions between H. hepaticus and intestinal macrophages that promote mutualism.
Effects of the intestinal microbiota on prostate cancer treatment by androgen deprivation therapy
November 15, 2022
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
September 23, 2022
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
June 27, 2022
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
June 22, 2022
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
May 19, 2022
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
February 18, 2022
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. (...)
An ionophore breaks the multi-drug-resistance of Acinetobacter baumannii
February 15, 2022
Within intensive care units, multi-drug resistant Acinetobacter baumannii outbreaks are a frequent cause of ventilator-associated pneumonia. During the on-going COVID-19 pandemic, patients who receive ventilator support experience a 2-fold increased risk of mortality when they contract a secondary A. baumannii pulmonary infection. In our recent paper (De Oliveira et al. (2022), Mbio, doi: 10.1128/mbio.03517-21), we demonstrate that the 8-hydroxquinoline ionophore, PBT2 breaks the resistance of A. baumannii to tetracycline class antibiotics. In vitro, the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecycline was shown to be bactericidal against multi-drug-resistant A. baumannii, (...)
Endomembrane remodeling and dynamics in Salmonella infection
December 27, 2021
Salmonellae are bacteria that cause moderate to severe infections in humans, depending on the strain and the immune status of the infected host. These pathogens have the particularity of residing in the cells of the infected host. They are usually found in a vacuolar compartment that the bacteria shape with the help of effector proteins. Following invasion of a eukaryotic cell, the bacterial vacuole undergoes maturation characterized by changes in localization, composition and morphology. In particular, membrane tubules stretching over the microtubule cytoskeleton are formed from the bacterial vacuole. Although these tubules do not occur in all infected cells, they are functionally important and promote intracellular replication. This review focuses on the role and significance of membrane compartment remodeling observed in infected cells and the bacterial and host cell pathways involved.