Review, Reviews
Forty-five-year evolution of probiotic therapy
Scarlett Puebla-Barragan1,2 and Gregor Reid1,2
The field of probiotics has greatly expanded over the past 45 years, driven by the need for safer alternatives to drugs, interest in natural microbial products, and clinical proof of effectiveness, with scientific formulations increasingly defining the market and promising applications for various health areas expected in the future.
Role of pheromone recognition systems in creating new species of fission yeast
Taisuke Seike1 and Chikashi Shimoda2
This article comments on work published by Seike at al. (PloS Biol., 2019), which demonstrated an “asymmetric” pheromone recognition system in the fission yeast Schizosaccharomyces pombe.
Adaptive bacterial response to low level chlorhexidine exposure and its implications for hand hygiene
Günter Kampf1
This article shows that bacteria can adapt to low levels of Chlorhexidine digluconate (CHG), resulting in increased tolerance and cross-resistance to other antimicrobials, suggesting caution in the widespread use of CHG to minimize avoidable selection pressure for resistance.
Microevolution of the pathogenic yeasts Candida albicans and Candida glabrata during antifungal therapy and host infection
Pedro Pais1,2,#, Mónica Galocha1,2,#, Romeu Viana1,2, Mafalda Cavalheiro1,2, Diana Pereira1,2, Miguel Cacho Teixeira1,2
This review explores how Candida albicans and Candida glabrata, common fungal pathogens resistant to antifungal therapy, adapt and evolve within different environments, aiming to identify stable adaptive mechanisms as potential drug targets.
The extracellular matrix of mycobacterial biofilms: could we shorten the treatment of mycobacterial infections?
Poushali Chakraborty1 and Ashwani Kumar1, 2
The article discusses the challenges presented by biofilms formed by non-tuberculous mycobacteria (NTM) species, which can lead to persistent infections that are difficult to treat due to phenotypic drug tolerance. The role of various cell wall components in mycobacterial biofilm formation is outlined, with a particular focus on Mycobacterium tuberculosis.
Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways
Hannah L. Klein1, Giedrė Bačinskaja2, Jun Che3, Anais Cheblal4, Rajula Elango5, Anastasiya Epshtein1, Devon M. Fitzgerald6-9, Belén Gómez-González10, Sharik R. Khan11, Sandeep Kumar7, Bryan A. Leland12, Léa Marie13, Qian Mei14, Judith Miné-Hattab16,17, Alicja Piotrowska18, Erica J. Polleys19, Christopher D. Putnam20,21, Elina A. Radchenko19, Anissia Ait Saada22,23, Cynthia J. Sakofsky24, Eun Yong Shim3, Mathew Stracy25, Jun Xia6-9, Zhenxin Yan7, Yi Yin26, Andrés Aguilera10, Juan Lucas Argueso27, Catherine H. Freudenreich19,28, Susan M. Gasser4, Dmitry A. Gordenin24, James E. Haber29, Grzegorz Ira7, Sue Jinks-Robertson30, Megan C. King12, Richard D. Kolodner20, 31-33, Andrei Kuzminov11, Sarah AE Lambert22,23, Sang Eun Lee3, Kyle M. Miller6,15, Sergei M. Mirkin19, Thomas D. Petes26, Susan M. Rosenberg6-9,14, Rodney Rothstein34, Lorraine S. Symington13, Pawel Zawadzki18, Nayun Kim35, Michael Lisby2 and Anna Malkova5
DNA recombination, repair and mutagenesis assays are powerful tools but each comes with its particular advantages and limitations. Here the most commonly used assays are reviewed, discussed, and presented as the guidelines for future studies.
Guidelines for DNA recombination and repair studies: Mechanistic assays of DNA repair processes
Hannah L Klein1, Kenny K.H. Ang2, Michelle R. Arkin2, Emily C. Beckwitt3,4, Yi-Hsuan Chang5, Jun Fan6, Youngho Kwon7,8, Michael J. Morten1, Sucheta Mukherjee9, Oliver J. Pambos6, Hafez el Sayyed6, Elizabeth S. Thrall10, João P. Vieira-da-Rocha9, Quan Wang11, Shuang Wang12,13, Hsin-Yi Yeh5, Julie S. Biteen14, Peter Chi5,15, Wolf-Dietrich Heyer9,16, Achillefs N. Kapanidis6, Joseph J. Loparo10, Terence R. Strick12,13,17, Patrick Sung7,8, Bennett Van Houten3,18,19, Hengyao Niu11 and Eli Rothenberg1
Mechanistic assays of DNA repair processes are a powerful tools but each comes with its particular advantages and limitations. Here the most commonly used assays are reviewed, discussed, and presented as the guidelines for future studies.
Imbalance in gut microbes from babies born to obese mothers increases gut permeability and myeloid cell adaptations that provoke obesity and NAFLD
Taylor K. Soderborg1 and Jacob E. Friedman1,2,3
This article comments on work published by Soderborg et al. (Nat Commun, 2018), which demonstrates a causative role of early life microbiome dysbiosis in infants born to mothers with obesity in novel pathways that promote developmental programming of NAFLD.
Retroviral integration site selection: a running Gag?
Paul Lesbats1,2,3 and Vincent Parissi1,2,3
In this article, the authors comment on the study "Structural basis for spumavirus GAG tethering to chromatin" by Lesbats et al. (Proc Natl Acad Sci, 2018) that revealed that the Gag protein of the spumaretrovirus prototype foamy virus (PFV) directly interacts with the nucleosome acidic patch, acting as a chromatin tether, and its disruption leads to delocalization of viral particles and integration sites, shedding light on the importance of retroviral structural proteins in the selection of integration sites.
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.