Microreviews, Review
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.
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. (...)
Francisella IglG protein and the DUF4280 proteins: PAAR-like proteins in non-canonical Type VI secretion systems?
October 30, 2016
This article comments on work published by Rigard et al. (PLoS Pathog, 2013), which identified the function of IgIG, a protein of unknown function, encoded within the Francisella Pathogenicity Island.
B cell-helping functions of gut microbial metabolites
September 23, 2016
This article comments on work published by Kim et al. (Cell Host & Microbe, 2016), which showed that the microbial metabolites short-chain fatty acids (SCFAs) regulate the metabolism and gene expression in B cells to promote antibody production.
How do yeast sense mitochondrial dysfunction?
September 22, 2016
Apart from energy transformation, mitochondria play important signaling roles. In yeast, mitochondrial signaling relies on several molecular cascades. However, it is not clear how a cell detects a particular mitochondrial malfunction. In our review we argue that in yeast the major known routes of mitochondrial signaling are moderated by non-mitochondrial inputs.
Chlamydia trachomatis Genital Infections
September 4, 2016
Chlamydia trachomatis infections are the most commonly reported sexually transmitted bacterial infections in the US and globally. Ascending infection may result in infertility, ectopic pregnancy and chronic pelvic pain in some women. In this review we provide an overview of current knowledge regarding epidemiology, disease outcomes and effective treatment of chlamydial genital tract infection and explore potential mechanisms facilitating C. trachomatis infection of genital mucosa identified via bioinformatics and other molecular approaches.
Hepatitis B virus and its sexually transmitted infection – an update
September 4, 2016
About 5% of the world’s population has chronic hepatitis B virus (HBV) infection, and nearly 25% of carriers develop chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The purpose of this article is to provide up-to-date information on HBV and HBV infection as a major sexually transmitted infection.
Gonorrhea – an evolving disease of the new millennium
September 4, 2016
Neisseria gonorrhoeae (the gonococcus) is a Gram-negative diplococcus, an obligate human pathogen, and the etiologic agent of the sexually transmitted disease, gonorrhea. This review provides insight into the molecular epidemiology, virulence mechanisms, pathogenesis and therapeutic options.
Cryptococcus flips its lid – membrane phospholipid asymmetry modulates antifungal drug resistance and virulence
August 1, 2016
This article comments on work published by Huang et al. (MBio, 2016), which reported that in the pathogenic fungus Cryptococcus neoformans loss of lipid flippase activity sensitized cryptococcal cells to multiple classes of antifungal drugs and abolished fungal virulence in murine models.
A novel component of the mitochondrial genome segregation machinery in trypanosomes
July 28, 2016
This article comments on work published by Trikin et al. (PLoS Pathog, 2016), which described a new component of the mitochondrial genome segregation machinery in the protozoan parasite Trypanosoma brucei.