Review, Reviews

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

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

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

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 <i>absent</i> protein function in yeast: assaying post translational modification and human genetic variation

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

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.

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When less is more: hormesis against stress and disease

May 5, 2014

This article condenses the conceptual and potentially therapeutic importance of hormesis by providing a short overview of current evidence in favor of the cytoprotective impact of hormesis, as well as of its underlying molecular mechanisms.

Morphed and moving: TNFα-driven motility promotes cell dissemination through MAP4K4-induced cytoskeleton remodeling

April 24, 2014

This article comments on work published by Ma and Baumgartner (PLoS Patho, 2014), which investigated Theileria parasite control of host cell motile properties in the context of inflammatory signaling.

Hormesis: a fundamental concept in biology

April 23, 2014

This article addresses the concept of hormetic dose response, which describes the limits to which integrative endpoints can be modulated (i.e., enhanced or diminished) by pharmaceutical, chemical and physical means.

Live longer on MARS: a yeast paradigm of mitochondrial adaptive ROS signaling in aging

April 23, 2014

In this article, the potential relevance of Mitochondrial Adaptive ROS Signaling (MARS) to the human disease Ataxia-Telangiectasia and as a potential anti-aging target is discussed.

Prokaryotic Argonautes – variations on the RNA interference theme

April 15, 2014

This article comments on work published by Swarts et al. (Nature, 2014), which demonstrates that Argonaute family protein of the bacterium Thermus thermophilus acts as a barrier for the uptake and propagation of foreign DNA.

Longevity pathways and maintenance of the proteome: the role of autophagy and mitophagy during yeast ageing

April 7, 2014

This review describes recent findings that shed light on how longevity pathways and metabolic status impact maintenance of the proteome in both yeast ageing paradigms. These findings demonstrate that yeast remain a powerful model system for elucidating these relationships and their influence on ageing regulation.

Secondary structures involving the poly(A) tail and other 3’ sequences are major determinants of mRNA isoform stability in yeast

April 5, 2014

This article comments on work published by Geisberg et al. (Cell (2014), which points to an important role for mRNA structure at 3’ termini in governing transcript stability, likely by reducing the interaction of the mRNA with the degradation apparatus.

De novo peroxisome biogenesis revisited

April 1, 2014

This article comments on work published by Knoops et al. (JCB, 2014), which describes an alternative peroxisome formation pathway in yeast pex3 and pex19 cells, which relies on the existence of small peroxisomal remnants that are present in these cells.

Transcriptional and genomic mayhem due to aging-induced nucleosome loss in budding yeast

April 1, 2014

This article comments on work published by Zheng et al. (Genes and Development, 2014), which investigated a loss of histones during replicative aging in budding yeast, which was also accompanied by a significantly-increased frequency of genomic instability including DNA breaks, chromosomal translocations, retrotransposition, and transfer of mitochondrial DNA into the nuclear genome.

The Parkinson’s disease-associated protein α-synuclein disrupts stress signaling – a possible implication for methamphetamine use?

March 31, 2014

This article comments on work published by Wang et al. (PNAS, 2012), which reported that human α-syn, at high expression levels, disrupts stress-activated signal transduction pathways in both yeast and human neuroblastoma cells. Disruption of these signaling pathways ultimately leads to vulnerability to stress and to cell death.

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