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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Bacterial genotoxin functions as immune-modulator and promotes host survival

July 28, 2016

This article comments on work published by Del Bel Belluz et al. (PLoS Pathog, 2016), which demonstrated that the typhoid toxin of Salmonella enterica serovar Typhi esembles an immune-modulatory molecule rather than a toxic agent.

Functions and regulation of the MRX complex at DNA double-strand breaks

July 27, 2016

DNA double-strand breaks (DSBs) pose a serious threat to genome stability and cell survival. Cells possess mechanisms that recognize DSBs and promote their repair through either homologous recombination (HR) or non-homologous end joining (NHEJ). The present review focuses mainly on recent works in the budding yeast Saccharomyces cerevisiae to highlight structure and regulation of the evolutionary conserved Mre11-Rad50-Xrs2 (MRX) complex as well as its interplays with Tel1.

Inhibition of Zika virus by Wolbachia in Aedes aegypti

June 27, 2016

This article comments on work published by Dutra et al. (Cell Host Microbe, 2016), which investigated the potential of Wolbachia infections in Aedes aegypti to restrict infection and transmission of Zika virus.

Syphilis: Re-emergence of an old foe

June 27, 2016

Syphilis is caused by infection with Treponema pallidum subsp. pallidum, a not-yet-cultivable spiral-shaped bacterium that is usually transmitted by sexual contact with an infected partner or by an infected pregnant woman to her fetus. This review provides insights into the etiology, epidemiology, clinical manifestation, diagnosis, treatment and prevention of syphilis.

Genital Herpes: Insights into Sexually Transmitted Infectious Disease

June 27, 2016

Genital herpes is one of the most common, persistent and highly infectious sexually transmitted viral infections. This review provides an insight into the epidemiology, pathology, our current understanding of the molecular mechanisms of infection and the currently available and upcoming treatments for genital herpes.

Trichomoniasis – are we giving the deserved attention to the most common non-viral sexually transmitted disease worldwide?

June 27, 2016

Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease (STD) in the world. This article contributes to claim the attention of public health policies to control this STD.

House of cellulose – a new hideout for drug tolerant Mycobacterium tuberculosis

June 23, 2016

This article comments on work published by Trivedi et al. (Nat Commun, 2016), which shows that Mycobacterium tuberculosis cells organise themselves into biofilms in response to intracellular thiol reductive stress.

Antibiotic use in childhood alters the gut microbiota and predisposes to overweight

June 20, 2016

This article comments on work published by Korpela et al. (Nat Commun, 2016), which investigates the correlation between the use of antibiotics in early life and the excessive weight gain in later childhood.

Evidence for the hallmarks of human aging in replicatively aging yeast

June 20, 2016

Recently, efforts have been made to characterize the hallmarks that accompany and contribute to the phenomenon of aging, as most relevant for humans. Remarkably, studying the finite lifespan of the single cell eukaryote budding yeast has been paramount for our understanding of aging. Here, we compile observations from literature over the past decades of research on replicatively aging yeast to highlight how the hallmarks of aging in humans are present in yeast.

Bacterial outer membrane vesicle biogenesis: a new mechanism and its implications

May 10, 2016

This article comments on work published by Roier et al. (Nat Commun, 2016), which proposes a novel and highly conserved bacterial outer membane vesicle biogenesis mechanism based on phospholipid accumulation in the outer leaflet of the outer membrane.

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