Microreviews
Swimming faster despite obstacles: a universal mechanism behind bacterial speed enhancement in complex fluids
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.
An ionophore breaks the multi-drug-resistance of Acinetobacter baumannii
David M.P. De Oliveira1 and Mark J. Walker1
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
Gabriela Leite1, Mark Pimentel1,2, Gillian M. Barlow1 and Ruchi Mathur1,3
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
Lisa C. Hennemann1,2 and Dao Nguyen1,2,3
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
Susan T. Lovett1
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
Julia C. V. Reuwsaat1, Tamara L. Doering2, and Livia Kmetzsch1,3
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.
Microbial hara-kiri: Exploiting lysosomal cell death in malaria parasites
January 12, 2015
The antimalarial drug chloroquine (CQ) has been sidelined in the fight against falciparum malaria due to wide-spread CQ resistance. This comment discusses the article "Validation of a chloroquine-induced cell death mechanism for clinical use against malaria" by Ch'ng et al. (2014), Cell Death Dis.
A pseudokinase couples signaling pathways to enable asymmetric cell division in a bacterium
December 30, 2014
In this article, the authors comment on the study "Cell fate regulation governed by a repurposed bacterial histidine kinase" by Childers et al., PLoS Biol. 2014 Oct 28;12(10):e1001979.
Targeting of chromatin readers: a novel strategy used by the Shigella flexneri virulence effector OspF to reprogram transcription
December 28, 2014
In this microreview, the authors discuss the article "Shigella flexneri targets the HP1γ subcode through the phosphothreoninelyase OspF" by Harouz et al. (2014), EMBO J, 22 : 2606-2622.
Plasmodium spp. membrane glutathione S-transferases: detoxification units and drug targets
October 23, 2014
This article comments on work published by Lisewski et al. (Cell, 2014), which reported the first examples of membrane-associated proteins in eicosanoid and glutathione metabolism members among Plasmodium spp.
Proline cis-trans isomerization is influenced by local lysine acetylation-deacetylation
October 23, 2014
This article comments on work published by Howe et al. (Mol Cell, 2014), which shows that local lysine acetylation and deacetylation modulate proline cis-trans isomerization in Saccharomyces cerevisiae.
On the link between cell cycle and infection of the Alphaproteobacterium Brucella abortus
September 29, 2014
This article comments on work published by Deghelt et al. (Nat Comm, 2014), which describe a cell cycle arrest and resume during the Brucella abortus trafficking in host cell, suggesting that like the model Alphaproteobacterium Caulobacter crescentus, these bacteria are able to block their cell cycle at the G1 phase when starvation is sensed.
Divide and conquer: processive transport enables multidrug transporters to tackle challenging drugs
September 23, 2014
This article comments on work published by Fluman et al. (Nat Comm, 2014), which describes the ability of bacterial multidrug transporters to move long molecules through the membrane in a processive manner.
The dual role of cyclin C connects stress regulated gene expression to mitochondrial dynamics
September 14, 2014
This work summarizes the role cyclin C plays in regulating stress-responsive transcription in the budding yeast Saccharomyces cerevisiae, including mitochondrial fission and regulated cell death.
Combinatorial stress responses: direct coupling of two major stress responses in Escherichia coli
September 1, 2014
This article comments on work published by Brown et al. (Nat Comm, 2014), which showed that the transcription of relA is activated by NtrC during nitrogen starvation, revealing that in E. coli and related bacteria, NtrC functions in combinatorial stress and serves to couple two major stress responses, the Ntr response and stringent response.
The replication timing program in the hands of two HDACs
July 25, 2014
This article comments on work published by Yoshida et al. (Mol Cell, 2014), which performed a systematic analysis of the role of histone deacetylases (HDACs) in the regulation of origin activity in budding yeast, finding that the epigenetic regulation of repetitive sequences is a key determinant of the DNA replication program.