Reviews

Regulation of anti-microbial autophagy by factors of the complement system

Christophe Viret1, Aurore Rozières1, Rémi Duclaux-Loras1, Gilles Boschetti1, Stéphane Nancey1 and
Mathias Faure1,2

This review explores emerging evidence that components of the complement system, beyond their traditional immune roles, modulate autophagy - particularly xenophagy - thereby influencing cell-autonomous antimicrobial responses during host-pathogen interactions.

Microfluidic techniques for separation of bacterial cells via taxis

Jyoti P. Gurung1, Murat Gel2,3 and Matthew A. B. Baker1,3

Microfluidic tools, ideal for studying microbial motility due to their control over laminar flows at microscopic scales, enable precise analysis of various taxis behaviors and have advanced applications in synthetic biology, directed evolution, and medical microbiology.

Influence of delivery and feeding mode in oral fungi colonization – a systematic review

Maria Joao Azevedo1,2,3,4, Maria de Lurdes Pereira1,5, Ricardo Araujo2,3,6, Carla Ramalho3,7,8, Egija Zaura4 and Benedita Sampaio-Maia1,2,3

A systematic review of oral fungal colonization in infants found that while breastfeeding did not significantly affect the oral mycobiome, vaginal delivery was associated with higher oral yeast colonization, particularly of Candida albicans.

The role of Lactobacillus species in the control of Candida via biotrophic interactions

Isabella Zangl1, Ildiko-Julia Pap2, Christoph Aspöck2 and Christoph Schüller1,3

Microbial communities, including Candida and Lactobacillus species, play a crucial role in human health, particularly in the context of mucosal infections, but our understanding of their interactions and effects is still incomplete due to the variability of species and isolates as well as the complexity of the human host.

Gut microbial metabolites in depression: understanding the biochemical mechanisms

Giorgia Caspani1, Sidney Kennedy2-5, Jane A. Foster6 and Jonathan Swann1

This article shows how the gut microbiota contributes to the pathophysiology of depression and examines the mechanisms by which microbially-derived molecules may influence depressive behavior, highlighting the potential of dietary interventions as novel therapeutic strategies.

The multiple functions of the numerous Chlamydia trachomatis secreted proteins: the tip of the iceberg

Joana N. Bugalhão1 and Luís Jaime Mota1

CThis article shows an in-depth review on the current knowledge and outstanding questions about secreted proteins from Chlamydia trachomatis, detailing their roles in host cell interaction and immune response evasion.

Diverse conditions support near-zero growth in yeast: Implications for the study of cell lifespan

Jordan Gulli1, Emily Cook1, Eugene Kroll1, Adam Rosebrock2,3, Amy Caudy2 and Frank Rosenzweig1

This review discusses alternative cultivation methods for baker's yeast to study its chronological lifespan, with the aim of better understanding the ageing of non-dividing cells and their potential implications for the lifespan of multicellular eukaryotes such as humans.

Integrins in disguise – mechanosensors in Saccharomyces cerevisiae as functional integrin analogues

Tarek Elhasi1 and Anders Blomberg1

This article shows that although yeast lack integrin-like proteins, they possess WSC- and MID-type mechanosensors that functionally resemble integrins in animal cells, playing a role in sensing external mechanical stimuli and activating the conserved PKC1-SLT1 cell wall integrity pathway, with potential implications for understanding mechanosensing in yeast biology.

Beyond cells – The virome in the human holobiont

Rodrigo García-López1,2,3, Vicente Pérez-Brocal1,2,3 and Andrés Moya1,2,3

This article provides an overview of viromics—viral metagenomics—and its evolution, highlighting the complexity and dynamic nature of viruses beyond their traditional view as pathogens. It acknowledges the technological advancements in molecular biology and sequencing that have allowed the field to grow, while also noting that viromic research still faces significant challenges and is not as developed as bacterial metagenomics. The review underscores the importance of viruses in various ecosystems, their role in shaping the genetic landscape, and their potential impact, and looks forward to future directions in viromic research.

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Effects of the intestinal microbiota on prostate cancer treatment by androgen deprivation therapy

November 15, 2022

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

September 23, 2022

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

June 27, 2022

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

June 22, 2022

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

May 19, 2022

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

February 28, 2022

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

February 18, 2022

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. (...)

An ionophore breaks the multi-drug-resistance of Acinetobacter baumannii

February 15, 2022

Within intensive care units, multi-drug resistant Acinetobacter baumannii outbreaks are a frequent cause of ventilator-associated pneumonia. During the on-going COVID-19 pandemic, patients who receive ventilator support experience a 2-fold increased risk of mortality when they contract a secondary A. baumannii pulmonary infection. In our recent paper (De Oliveira et al. (2022), Mbio, doi: 10.1128/mbio.03517-21), we demonstrate that the 8-hydroxquinoline ionophore, PBT2 breaks the resistance of A. baumannii to tetracycline class antibiotics. In vitro, the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecycline was shown to be bactericidal against multi-drug-resistant A. baumannii, (...)

Endomembrane remodeling and dynamics in Salmonella infection

December 27, 2021

Salmonellae are bacteria that cause moderate to severe infections in humans, depending on the strain and the immune status of the infected host. These pathogens have the particularity of residing in the cells of the infected host. They are usually found in a vacuolar compartment that the bacteria shape with the help of effector proteins. Following invasion of a eukaryotic cell, the bacterial vacuole undergoes maturation characterized by changes in localization, composition and morphology. In particular, membrane tubules stretching over the microtubule cytoskeleton are formed from the bacterial vacuole. Although these tubules do not occur in all infected cells, they are functionally important and promote intracellular replication. This review focuses on the role and significance of membrane compartment remodeling observed in infected cells and the bacterial and host cell pathways involved.

The small bowel microbiome changes significantly with age and aspects of the ageing process

December 27, 2021

Gut microbiome changes have been associated with human ageing and implicated in age-related diseases including Alzheimer’s disease and Parkinson’s disease. However, studies to date have used stool samples, which do not represent the entire gut. Although more challenging to access, the small intestine plays critical roles in host metabolism and immune function. In this paper (Leite et al. (2021), Cell Reports, doi: 10.1016/j.celrep.2021.109765), we demonstrate significant differences in the small intestinal microbiome in older subjects, (...)

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