Review, Reviews
Proline cis-trans isomerization is influenced by local lysine acetylation-deacetylation
Françoise S. Howe and Jane Mellor
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
Michaël Deghelt, Jean-Jacques Letesson, Xavier De Bolle
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
Nir Fluman and Eitan Bibi
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
Randy Strich and Katrina F. Cooper
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
Daniel R. Brown, Geraint Barton, Zhensheng Pan, Martin Buck and Sivaramesh Wigneshweraraj
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
Kazumasa Yoshida1,2, Armelle Lengronne1 and Philippe Pasero1
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.
Increased Trypanosoma brucei cathepsin-L activity inhibits human serum-mediated trypanolysis
Sam Alsford
This article comments on work published by Alsford et al. (PLoS Pathogens, 2014), which identified a Trypanosoma brucei lysosomal cathepsin with an inhibitory effect on human serum’s trypanolytic action.
A novel role of centrin in flagellar motility: stabilizing an inner-arm dynein motor in the flagellar axoneme
Ziyin Li
This article comments on work published by Wei et al. (Nat Comm, 2014), which discovered that centrin maintains the stability of an inner-arm dynein in the flagellar axoneme in Trypanosoma brucei.
A non-proteolytic function of ubiquitin in transcription repression
Ada Ndoja and Tingting Yao
This article comments on work published by Ndoja et al. (Mol Cell, 2014), which demonstrates that monoubiquitination of some transcription activators can inhibit transcription by recruiting the AAA+ ATPase Cdc48 (also known in metazoans as p97 or VCP), which then extracts the ubiquitinated activator from DNA.
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.
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.