Reviews
Mechanisms underlying lactic acid tolerance and its influence on lactic acid production in Saccharomyces cerevisiae
Arne Peetermans1,2, María R. Foulquié-Moreno1,2 and Johan M. Thevelein1,2,3
This article reviews the manner in which Saccharomyces cerevisiae deals with the accumulation of lactic acid as a singular stress factor as well as in combination with other stresses. In addition, different methods to improve lactic acid tolerance in S. cerevisiae using targeted and non-targeted engineering methods are discussed.
Biofilms by bacterial human pathogens: Clinical relevance – development, composition and regulation – therapeutical strategies
Adina Schulze1,#, Fabian Mitterer1,#, Joao P. Pombo1 and Stefan Schild1,2,3
This review focuses on bacterial biofilms formed by human pathogens, highlights their relevance for diverse diseases and discusses therapeutical intervention strategies targeting biofilms.
Milestones in Bacillus subtilis sporulation research
Eammon P. Riley1, Corinna Schwarz2, Alan I. Derman2 and Javier Lopez-Garrido2
In this review, the foundational discoveries that shaped the sporulation field are discussed, from its origins to the present day, tracing a chronology that spans more than one hundred eighty years.
Extracellular vesicles: An emerging platform in gram-positive bacteria
Swagata Bose1,#, Shifu Aggarwal1,#, Durg Vijai Singh1,2 and Narottam Acharya1
Extracellular vesicles (EVs) are secreted by both pathogenic and non-pathogenic bacteria to transfer biomolecules and facilitate intercellular communication. While EV secretion in gram-negative bacteria is well understood, less is known about gram-positive bacteria. This review explores the role of EVs involved in bacterial competition, survival, immune evasion, and infection of gram-positive bacteria and compares them to gram-negative counterparts.
Structural insights into the architecture and assembly of eukaryotic flagella
Narcis-Adrian Petriman1 and Esben Lorentzen1
Cilia and flagella are key structures in motility and signaling. This review highlights recent findings of cryo-EM studies that have mapped the structure of axonemal microtubules in Chlamydomonas reinhardtii, revealing over 30 associated proteins as well as recent researcht which focused on the trafficking complexes that transport components between the cell body and cilium.
Plant and fungal products that extend lifespan in Caenorhabditis elegans
Jan Martel1,2, Cheng-Yeu Wu1-3, Hsin-Hsin Peng1,2,4, Yun-Fei Ko2,5,6, Hung-Chi Yang7, John D. Young5 and David M. Ojcius1,2,8
Caenorhabditis elegans' lifespan is extended by plant and fungal extracts activating pathways like autophagy and mitochondrial biogenesis. Low to moderate concentrations promote longevity, while high doses are harmful. This review explores the health benefits of these substances in humans.
From the Uncharacterized Protein Family 0016 to the GDT1 family: Molecular insights into a newly-characterized family of cation secondary transporters
Louise Thines1, Jiri Stribny1 and Pierre Morsomme1
This review outlines how the formerly uncharacterized UPF0016 family, now known as the Gdt1 family, plays key roles in cation transport - especially Mn²⁺ - across species from bacteria to humans. These proteins are crucial for processes like glycosylation, photosynthesis, and calcium signaling, with functions linked to their localization in membranes such as the Golgi, chloroplast, and plasma membrane and by that highlighting their evolutionary conservation and physiological relevance, offering insights into their shared and distinct features across organisms.
Regulation of Cdc42 for polarized growth in budding yeast
Kristi E. Miller1,2, Pil Jung Kang1 and Hay-Oak Park1
This review highlights how studies in budding yeast have revealed a biphasic mechanism of Cdc42 activation that governs cell polarity establishment, with implications for understanding similar processes in mammalian cells and the role of Cdc42 in aging.
Yeast-based assays for the functional characterization of cancer-associated variants of human DNA repair genes
Tiziana Cervelli1, Samuele Lodovichi1, Francesca Bellè1 and Alvaro Galli1
This article highlights how the genetic tractability and conserved DNA repair pathways of yeast make it a powerful system for functionally characterizing human cancer-associated variants in DNA repair genes, aiding in risk assessment and therapeutic decision-making.
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.
The small bowel microbiome changes significantly with age and aspects of the ageing process
December 27, 2021
Gut microbiome changes have been associated with human ageing and implicated in age-related diseases including Alzheimer’s disease and Parkinson’s disease. However, studies to date have used stool samples, which do not represent the entire gut. Although more challenging to access, the small intestine plays critical roles in host metabolism and immune function. In this paper (Leite et al. (2021), Cell Reports, doi: 10.1016/j.celrep.2021.109765), we demonstrate significant differences in the small intestinal microbiome in older subjects, (...)