Microreviews
A novel c-di-GMP signal system regulates biofilm formation in Pseudomonas aeruginosa
Gukui Chen1 and Haihua Liang1
This article relates to the study "The SiaA/B/C/D signaling network regulates biofilm formation in Pseudomonas aeruginosa" by Chen et al. (EMBO J, 2020) that reveals a novel signaling network encoded by the siaABCD operon in Pseudomonas aeruginosa that regulates biofilm and aggregate formation by controlling the diguanylate cyclase activity of SiaD through phosphorylation-dependent interactions with SiaC, highlighting a potential antimicrobial target.
More than flipping the lid: Cdc50 contributes to echinocandin resistance by regulating calcium homeostasis in Cryptococcus neoformans
Chengjun Cao1 and Chaoyang Xue1,2
In this article, the authors comment on the study "A mechanosensitive channel governs lipid flippase-mediated echinocandin resistance in Cryptococcus neoformans" by Cao et al. (mBio, 2019), which uncovers a dual role for the lipid flippase subunit Cdc50 in Cryptococcus neoformans, linking lipid translocation and calcium signaling via its interaction with the mechanosensitive channel Crm1, thereby contributing to innate resistance against the antifungal drug caspofungin.
New insights in the mode of action of anti-leishmanial drugs by using chemical mutagenesis screens coupled to next-generation sequencing
Arijit Bhattacharya1, Sophia Bigot2, Prasad Kottayil Padmanabhan2, Angana Mukherjee2, Adriano Coelho3, Philippe Leprohon2, Barbara Papadopoulou2 and Marc Ouellette2
In this article, the authors comment on the study "Coupling chemical mutagenesis to next generation sequencing for the identification of drug resistance mutations in Leishmania" by Bhattacharya et al. (Nat Commun, 2019), which introduces Mut-seq, a chemical mutagenesis and sequencing approach, to uncover drug resistance mechanisms in Leishmania, revealing links between lipid metabolism genes and miltefosine resistance, and a protein kinase involved in translation conferring paromomycin resistance.
A holobiont view on thrombosis: unravelling the microbiota’s influence on arterial thrombus growth
Giulia Pontarollo1, Klytaimnistra Kiouptsi1 and Christoph Reinhardt1,2
In this article, the authors comment on the study "The microbiota promotes arterial thrombosis in low-density lipoprotein receptor-deficient mice" by Kiouptsi et al. (mBio, 2019) that showed that commensal microbiota, intricately linked to host physiology, may influence cardiovascular disease, as shown by studies using germ-free atherosclerosis-prone mice to examine how microbial presence and diet affect arterial thrombosis and lesion development.
Tribal warfare: Commensal Neisseria kill pathogen Neisseria gonorrhoeae using its DNA
Magdalene So1 and Maria A. Rendón1
This article comments on work published by Kim et al (Cell Host Microbe, 2019), which adds a new dimension to the concept of commensal protection. It shows that commensal Neisseria kill the closely related pathogen N. gonorrhoeae through an unexpected mechanism, one that involves genetic competence, DNA methylation state and recombination.
Yet another job for the bacterial ribosome
Andrea Origi1,2, Ana Natriashivili1,2, Lara Knüpffer1, Clara Fehrenbach1, Kärt Denks1,2, Rosella Asti1 and Hans-Georg Koch1
This article comments on work published by Knüpffer et al (mBio, 2019), which revealed the intricate interaction of uL23 with yet another essential player in bacteria, the ATPase SecA, which is best known for its role during post-translational secretion of proteins across the bacterial SecYEG translocon
Inhibiting eukaryotic ribosome biogenesis: Mining new tools for basic research and medical applications
Lisa Kofler1, Michael Prattes1 and Helmut Bergler1
This article comments on work published by Awad et al (BMC Biology, 2019), which screened for novel inhibitors of the ribosome biogenesis pathway in yeast.
Evolution of the bacterial nucleosidase PpnN and its relation to the stringent response
René Lysdal Bærentsen1, Ditlev Egeskov Brodersen1 and Yong Everett Zhang2
This article comments on work published by Zhang et al (Mol Cell, 2019), which discovered an interesting mode of regulation of purine metabolism unique to Proteobacteria.
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.
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, (...)
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, (...)
LasR-regulated proteases in acute vs. chronic lung infection: a double-edged sword
May 31, 2021
This article comments on work published by Hennemann et al. (PLoS Pathog, 2021), which observed that in Pseudomonas aeruginosa, functional loss of the quorum sensing transcriptional activator LasR in lasR variants results in impaired secreted protease production, leads to increased expression of the membrane-bound surface adhesion molecule mICAM-1 in the airway epithelium, and increases neutrophilic inflammation.
DNA polymerase III protein, HolC, helps resolve replication/transcription conflicts
May 6, 2021
This article comments on work published by Cooper et al. (mBio, 2021), which isolated and identified spontaneous suppressor mutants in a strain devoid of the holC gene, which encodes an accessory protein to the core clamp loader complex and is the only protein of the DNA polymerase III holoenzyme that binds to single-strand DNA binding protein.
Too much of a good thing: Overproduction of virulence factors impairs cryptococcal pathogenicity
April 20, 2021
This article comments on work published by Reuwsaat et al. (mBio, 2021), which identified the transcription factor Pdr802 as essential for Cryptococcus neoformans adaptation to and survival under host conditions both in vitro and in vivo.