Review, Reviews

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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pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity

January 12, 2018

In this article, Deprez et al. discuss accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

Guidelines and recommendations on yeast cell death nomenclature

January 1, 2018

In this review, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of yeast.

Burkholderia gladioli strain NGJ1 deploys a prophage tail-like protein for mycophagy

December 31, 2017

In this article, the authors comment on the study "A prophage tail-like protein is deployed by Burkholderia bacteria to feed on fungi" by Swain et al. (Nature Communications, 2017), discussing that a prophage tail-like protein (Bg_9562) is essential for mycophagy. The protein may help the bacteria to survive in certain ecological niches and, considering its broad-spectrum antifungal activity, may be potentially useful in biotechnological applications to control fungal diseases.

Ras signalling in pathogenic yeasts

December 18, 2017

In this article Pentland et al. review the roles of Ras protein function and signalling in the major human yeast pathogens Candida albicans and Cryptococcus neoformans and discuss the potential for targeting Ras as a novel approach to anti-fungal therapy.

The logics of metabolic regulation in bacteria challenges biosensor-based metabolic engineering

December 11, 2017

In this article, the authors comment on the study "Molecular and Physiological Logics of the Pyruvate-Induced Response of a Novel Transporter in Bacillus subtilis" by Charbonnier et al. (mBio, 2017), which identified and characterized a pyruvate transport system in the Gram-positive (G+ve) bacterium Bacillus subtilis, a well-established biotechnological workhorse for the production of enzymes, fine chemicals and antibiotics.

A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori

December 9, 2017

In this article, the authors comment on the study "Helicobacter pylori Employs a Unique Basolateral Type IV Secretion Mechanism for CagA Delivery" by Tegtmeyer et al. (Cell Host Microbe, 2017), discussing that the finding of a T4SS receptor suggests the presence of a sophisticated control mechanism for the injection of CagA and the possible impact of this novel signaling cascade on pathogenesis during infection with Helicobacter pylori.

A new role for the nuclear basket network

November 28, 2017

This article comments on work published by Salas-Pino et al. (J Cell Biol, 2017), which describes a novel function of the fission yeast nuclear basket component - the translocated promoter region (TPR) nucleoporin Alm1 - in proper localization of the proteasome to the nuclear envelope.

VAMP8 mucin exocytosis attenuates intestinal pathogenesis by Entamoeba histolytica

November 24, 2017

This article comments on work published by Cornick et al. (mBio, 2017), which nominates SNARE-mediated exocytosis as the putative mechanism responsible for pathogen-induced mucus secretion from goblet cells.

Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase

November 3, 2017

This article comments on work published by Davis et al. (mBio, 2017), which describes molecular requirements that govern NSP1 recognition of β-TrCP, including an essential degron phosphorylation event, and the step-wise incorporation of NSP1 into hijacked cullin-RING E3 ligases (CRLs) that ubiquitinate and tag β-TrCP for degradation.

Breaking the bad: Bacillus blocks fungal virulence factors

October 30, 2017

This article comments on work published by Mayer & Kronstad (mBio, 2017), which identified the soil bacterium, Bacillus safensis as a potent inhibitor of virulence factor production by two major fungal pathogens of humans, Cryptococcus neoformans, and Candida albicans.

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