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
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.
Forty-five-year evolution of probiotic therapy
April 2, 2019
The field of probiotics has greatly expanded over the past 45 years, driven by the need for safer alternatives to drugs, interest in natural microbial products, and clinical proof of effectiveness, with scientific formulations increasingly defining the market and promising applications for various health areas expected in the future.
Role of pheromone recognition systems in creating new species of fission yeast
March 11, 2019
This article comments on work published by Seike at al. (PloS Biol., 2019), which demonstrated an “asymmetric” pheromone recognition system in the fission yeast Schizosaccharomyces pombe.
Adaptive bacterial response to low level chlorhexidine exposure and its implications for hand hygiene
March 7, 2019
This article shows that bacteria can adapt to low levels of Chlorhexidine digluconate (CHG), resulting in increased tolerance and cross-resistance to other antimicrobials, suggesting caution in the widespread use of CHG to minimize avoidable selection pressure for resistance.
Microevolution of the pathogenic yeasts Candida albicans and Candida glabrata during antifungal therapy and host infection
February 8, 2019
This review explores how Candida albicans and Candida glabrata, common fungal pathogens resistant to antifungal therapy, adapt and evolve within different environments, aiming to identify stable adaptive mechanisms as potential drug targets.
The extracellular matrix of mycobacterial biofilms: could we shorten the treatment of mycobacterial infections?
January 18, 2019
The article discusses the challenges presented by biofilms formed by non-tuberculous mycobacteria (NTM) species, which can lead to persistent infections that are difficult to treat due to phenotypic drug tolerance. The role of various cell wall components in mycobacterial biofilm formation is outlined, with a particular focus on Mycobacterium tuberculosis.
Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways
January 7, 2019
DNA recombination, repair and mutagenesis assays are powerful tools but each comes with its particular advantages and limitations. Here the most commonly used assays are reviewed, discussed, and presented as the guidelines for future studies.
Guidelines for DNA recombination and repair studies: Mechanistic assays of DNA repair processes
January 7, 2019
Mechanistic assays of DNA repair processes are a powerful tools but each comes with its particular advantages and limitations. Here the most commonly used assays are reviewed, discussed, and presented as the guidelines for future studies.
Imbalance in gut microbes from babies born to obese mothers increases gut permeability and myeloid cell adaptations that provoke obesity and NAFLD
December 19, 2018
This article comments on work published by Soderborg et al. (Nat Commun, 2018), which demonstrates a causative role of early life microbiome dysbiosis in infants born to mothers with obesity in novel pathways that promote developmental programming of NAFLD.
Retroviral integration site selection: a running Gag?
November 19, 2018
In this article, the authors comment on the study "Structural basis for spumavirus GAG tethering to chromatin" by Lesbats et al. (Proc Natl Acad Sci, 2018) that revealed that the Gag protein of the spumaretrovirus prototype foamy virus (PFV) directly interacts with the nucleosome acidic patch, acting as a chromatin tether, and its disruption leads to delocalization of viral particles and integration sites, shedding light on the importance of retroviral structural proteins in the selection of integration sites.
Insights into the host-pathogen interaction: C. albicans manipulation of macrophage pyroptosis
November 12, 2018
In this article, the authors comment on the study "High-Throughput Screening Identifies Genes Required for Candida albicans Induction of Macrophage Pyroptosis" by O’Meara et al. (MBio, 2018) that provides a comprehensive analysis of the genetic circuitry in both Candida albicans and host macrophages that leads to pyroptosis, revealing the impact of altered pyroptosis on infection, the role of pyroptosis in facilitating neutrophil accumulation at the site of C. albicans infection, and the decoupling of inflammasome priming and activation in the response to C. albicans infection, thus shedding new light on the factors governing the outcomes of this interaction.