Microreviews, Review

Infinity war: <i>Trichomonas vaginalis</i> and interactions with host immune response

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

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

Shashank Kamdar1 and Xiang Cheng1

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.

Fatty acid metabolism of Mycobacterium tuberculosis: A double-edged sword

Camila G. Quinonez1,2, Jae Jin Lee1, Juhyeon Lim1, Mark Odell3, Christopher P. Lawson4, Amarachukwu Anyogu5, Saki Raheem2 and Hyungjin Eoh1

Unlike other heterotrophic bacteria, Mycobacterium tuberculosis (Mtb) can co-catabolize a range of carbon sources simultaneously. Evolution of Mtb within host nutrient environment allows Mtb to consume the host’s fatty acids as a main carbon source during infection. The fatty acid-induced metabolic advantage greatly contributes to Mtb’s pathogenicity and virulence. Thus, the identification of key enzymes involved in Mtb’s fatty acid metabolism is urgently needed to aid new drug development. Two fatty acid metabolism enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and isocitrate lyase (ICL) have been intensively studied as promising drug targets, but recently, Quinonez et al. (mBio, doi: 10.1128/mbio.03559-21) highlighted a link between the fatty acid-induced dormancy-like state and drug tolerance. (...)

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. (...)

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Gammaretroviruses tether to mitotic chromatin by directly binding nucleosomal histone proteins

July 24, 2018

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

June 14, 2018

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

May 17, 2018

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

May 16, 2018

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.

A novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases

April 11, 2018

In this article, the authors comment on the study "Herpesvirus deconjugases inhibit the IFN response by promoting TRIM25 autoubiquitination and functional inactivation of the RIG-I signalosome" by Gupta et al. (PLoS Pathog, 2018), discussing the finding of a novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases.

Metabolic disharmony and sibling conflict mediated by T6SS

April 4, 2018

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

March 22, 2018

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.

Endolysosomal pathway activity protects cells from neurotoxic TDP-43

March 21, 2018

In this article, the authors comment on the study "TDP-43 controls lysosomal pathways thereby determining its own clearance and cytotoxicity" by Leibiger et al. (Hum Mol Genet, 2018), proposing that ameliorating endolysosomal pathway activity enhances cell survival in TDP‑43-associated diseases.

Two distinct penicillin binding proteins promote cell division in different Salmonella lifestyles

February 18, 2018

In this article, the authors comment on the study "A Specialized Peptidoglycan Synthase Promotes Salmonella Cell Division inside Host Cells" by Castanheira et al. (mBio, 2017), discussing insights in two distinct penicillin binding proteins that promote cell division in different Salmonella lifestyles.

New perspectives from South-Y-East, not all about death

A report of the 12th lnternational Meeting on Yeast Apoptosis in Bari, Italy, May 14th-18th, 2017

January 16, 2018

In this article Guaragnella et al. report on the 12th International Meeting on Yeast Apoptosis (IMYA12), which was held in Bari, Italy from May 14th to 18th, 2017, where more than 100 participants, among which senior and young scientists from Europe, USA, North Africa and Japan, had an intense and open exchange of achievements and ideas in the field of yeast regulated cell death (RCD).

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