Microreviews, Review
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, (...)
Endomembrane remodeling and dynamics in Salmonella infection
Ziyan Fang1 and Stéphane Méresse1
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
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, (...)
Lipid and fatty acid metabolism in trypanosomatids
Giovana Parreira de Aquino1,#, Marco Antonio Mendes Gomes1,#, Roberto Köpke Salinas2 and Maria Fernanda Laranjeira-Silva1
This work reviews specific aspects of lipid and fatty acid metabolism in the protozoan parasites T. brucei, T. cruzi, and Leishmania spp., as well as the pathways that have been explored for the development of new chemotherapies.
Using microbial metalo-aminopeptidases as targets in human infectious diseases
Jorge González-Bacerio1,2, Maikel Izquierdo1, Mirtha Elisa Aguado1, Ana C. Varela1, Maikel González-Matos1 and Maday Alonso del Rivero1
This Review highlights the relevant roles of microbial metalo-aminopeptidases in bacteria and protozoa that could be targeted for therapeutic purposes.
Understanding the pathogenesis of infectious diseases by single-cell RNA sequencing
Wanqiu Huang1, Danni Wang1 and Yu-Feng Yao1,2
This work highlights recent remarkable advances in single-cell RNA sequencing technologies and their applications in the investigation of host-pathogen interactions. Current challenges and potential prospects for disease treatment are discussed as well.
Exploring absent protein function in yeast: assaying post translational modification and human genetic variation
Christina S. Moesslacher1,#, Johanna M. Kohlmayr1,# and Ulrich Stelzl1,#
This review discusses the applicability of yeast systems to investigate absent human protein function with a specific focus on the impact of protein variation on protein-protein interaction modulation.
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.
A plant Bcl-2-associated athanogene is proteolytically activated to confer fungal resistance
April 16, 2016
This article comments on work published by Li et al. (Plant Cell, 2016), which focuses on the role of Bcl-2-associated athanogene 6 (BAG6) in plant innate immunity, showing that BAG6 plays a key role in basal plant defense against fungal pathogens.
The molecular and cellular action properties of artemisinins: what has yeast told us?
April 14, 2016
Artemisinin (ART) or Qinghaosu is a natural compound possessing superior anti-malarial activity. Although intensive studies have been done in the medicinal chemistry field to understand the structure-effect relationship, the biological actions of artemisinin are poorly understood and controversial. This review summarizes what we have learned from yeast about the basic biological properties of ARTs, as well as some key unanswered questions.
Chemical proteomics approach reveals the direct targets and the heme-dependent activation mechanism of artemisinin in Plasmodium falciparum using an activity-based artemisinin probe
April 5, 2016
This article comments on work published by Wang et al. (Nat Commun, 2014), which provides insights into the mode-of-action of artemisinin and its specificity against malaria parasites.
Translational repression in malaria sporozoites
April 5, 2016
This article comments on work published by Zhang et al. (PLoS Pathog, 2016), which summarizea recent advances in the translational repression of gene expression in the malaria sporozoite.
Chromatin binding and silencing: Two roles of the same protein Lem2
April 4, 2016
This article comments on work published by Barrales et al. (Genes Dev, 2016), which identifies the nuclear envelope protein Lem2, a homolog of metazoan lamin-associated proteins (LAPs), as a relevant factor for heterochromatin silencing and perinuclear localization in the fission yeast Schizosaccharomyces pombe.
When and where? Pathogenic Escherichia coli differentially sense host D-serine using a universal transporter system to monitor their environment
March 31, 2016
This article comments on work published by Connolly et al. (PLoS Pathog, 2016), which describes the discovery of a functional and previously uncharacterized D-serine uptake system in E. coli.
Signaling pathways and posttranslational modifications of tau in Alzheimer’s disease: the humanization of yeast cells
March 27, 2016
In the past decade, yeast have been frequently employed to study the molecular mechanisms of human neurodegenerative diseases, generally by means of heterologous expression of genes encoding the relevant hallmark proteins. Substantial posttranslational modifications of many of these proteins are required for the development and progression of potentially disease relevant changes. We give an overview on common modifications as they occur in tau during AD and discuss potential approaches to humanize yeast in order to create modification patterns resembling the situation in mammalian cells.
The bacterial cell cycle checkpoint protein Obg and its role in programmed cell death
March 16, 2016
This article comments on work published by Dewachter et al. (mBio, 2015), which identified a programmed cell death mechanism in Escherichia coli that is triggered by a mutant isoform of the essential GTPase ObgE.