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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Inhibitors of glycosomal protein import provide new leads against trypanosomiasis

July 3, 2017

This article comments on work published by Dawidowski et al. (Science, 2017), which provides the grounds for further development of the glycosome inhibitors into clinical candidates and validates the parasite protein-protein interactions as drug targets.

Impact of the host on Toxoplasma stage differentiation

June 22, 2017

This review summarizes how Toxoplasma gondii transitions from an acute to a chronic infection in warm-blooded animals and humans through a developmental switch influenced by host cell physiology, which determines parasite persistence mainly in neural and muscular tissues.

Chlamydia and mitochondria – an unfragmented relationship

June 14, 2017

This article comments on work published by Chowdhury et al (J Cell Biol, 2017), which demonstrated that Chlamydia infection induces and requires an upregulation of the host miRNA, miR-30c-5p (miR-30c) to ameliorate infection induced stress on the host mitochondrial architecture and hinders induction of apoptosis.

Protein aggregation triggers a declining libido in elder yeasts that still have a lust for life

May 29, 2017

This article comments on work published by Schlissel et al (Science 2017), showing that aging in yeast does not lead to the expected loss of heterochromatin silencing due to Sir2 inactivity, but rather to reduced mating pheromone sensitivity caused by the aggregation of the RNA-binding protein Whi3, which can be reversed by eliminating Whi3's polyglutamine domain.

Post-transcriptional regulation of ribosome biogenesis in yeast

May 1, 2017

Microorganisms adapt to environmental changes by regulating their metabolism, and one key survival strategy is to decrease energy use during adverse conditions by halting ribosome production, with recent findings showing yeast can switch between pre-rRNA processing pathways in response to environmental shifts, adding complexity to ribosome biogenesis regulation.

Placeholder factors in ribosome biogenesis: please, pave my way

April 27, 2017

In ribosome synthesis, "placeholder" factors are crucial trans-acting elements that regulate the timing and assembly of ribosomal proteins, ensuring speed and accuracy in this intricate process by preventing premature interactions and guiding the proper formation of functional ribosomal subunits.

Insights from the redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains

April 25, 2017

This article comments on work published by Li et al. (PloS Pathog, 2017), focusing on Helicobacter pylori infections. They are mostly asymptomatic but can lead to serious conditions, and H. pylori lipopolysaccharide (LPS) is crucial for colonization and persistence, making the study of its structure and biosynthesis pathway vital for understanding pathogenesis and developing treatments.

Evading plant immunity: feedback control of the T3SS in Pseudomonas syringae

March 17, 2017

This article comments on work published by Waite et al. (mBio, 2017), which indicates that a negative autogenous control mechanism, where the sigma factor HrpL represses its own expression, permits the plant pathogen Pseudomonas syringae to fine-tune its type III secretion system, potentially reducing the elicitation of plant immunity and enhancing its ability to cause disease.

Microbial flora, probiotics, Bacillus subtilis and the search for a long and healthy human longevity

March 16, 2017

This article comments on work published by Donato et al. (Nat Commun, 2017), which reveals that the probiotic Bacillus subtilis extends the lifespan of Caenorhabditis elegans via mechanisms including the formation of biofilms and the production of signaling molecules like NO and CSF, suggesting a potential pathway through insulin-like signaling that could impact human longevity and age-related diseases.

Chlamydia trachomatis’ struggle to keep its host alive

March 2, 2017

This article comments on work published by Sixt et al. (Cell Host Microbe, 2016), which analyzed a CpoS-deficient mutant yielding unique insights into the nature of cell-autonomous defense responses against Chlamydia.

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