Microreviews, Review
Pirates of the haemoglobin
Daniel Akinbosede1, Robert Chizea1 and Stephen A. Hare1,†
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
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.
When the pandemic opts for the lockdown: Secretion system evolution in the cholera bacterium
February 18, 2021
This article comments on work published by Santoriello et al. (Nat Comm, 2020), which demonstrates that the T6SS island Auxiliary Cluster 3 (Aux3) is unique to pandemic strains of V. cholerae.
Maintaining phagosome integrity during fungal infection: do or die?
December 3, 2020
This article refers to the paper "Lysosome Fusion Maintains Phagosome Integrity during Fungal Infection" by Westman et al. (Cell Host Microbe, 2020), which shows that macrophages respond to pathogen growth by expanding the phagosome membrane through a calcium-dependent mechanism involving lysosome insertion, maintaining membrane integrity and preventing rupture.
A novel antibacterial strategy: histone and antimicrobial peptide synergy
October 8, 2020
This article refers to the study "Mammalian histones facilitate antimicrobial synergy by disrupting the bacterial proton gradient and chromosome organization" by Doolin et al. (Nat Comm, 2020) that shows that histones enhance the antimicrobial activity of peptides, disrupt bacterial membranes, and inhibit transcription, offering new insights into natural antimicrobial mechanisms.
Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparum
September 16, 2020
This article refers to the study "Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention" by Adderley et al. (Nat Commun, 2020) that investigates how Plasmodium falciparum malaria parasites influence red blood cells. By tracking hanges in over 800 human proteins at different parasite stages they confirmed activation of the PAK-MEK pathway and discovered significant changes, particularly during the trophozoite stage. This suggests that kinases activated by the infection could be targeted for new antimalarial therapies.
A new role for proteins subunits of RNase P: stabilization of the telomerase holoenzyme
June 17, 2020
This article refers to the study "Stability and Nuclear Localization of Yeast Telomerase Depend on Protein Components of RNase P/MRP", by Garcia et al. (Nat Commun, 2020), showing that 3 essential proteins in Saccharomyces cerevisiae are vital for telomerase assembly and nuclear localization. In their mutants, telomerase is less mature, and telomeres are shorter. TLC1 is properly folded but remains in the cytoplasm, rather than moving to the nucleus, where it maintains telomeres.
Lipid droplet biogenesis from specialized ER subdomains
June 16, 2020
This article refers to the paper "Seipin and Nem1 establish discrete ER subdomains to initiate yeast lipid droplet biogenesis" by Choudhary et al. (J Cell Biol, 2020), which deals with the formation of lipid droplets (LDs) at specific ER sites marked by the proteins Fld1 and Nem1. These proteins recruit enzymes such as Lro1 and Dga1 to initiate fat storage. Together, Fld1 and Nem1 define where LDs form by organising key proteins and lipids needed for their biogenesis.
A broad-spectrum antibiotic adjuvant SLAP-S25: one stone many birds
June 15, 2020
This article refers to the study "A broad-spectrum antibiotic adjuvant reverses multidrug-resistant Gram-negative pathogens" by Song et al. (Nat Microbiol, 2020), which deals with the growing threat of antibiotic resistance, with few new drugs being developed for decades. The study found that the peptide SLAP-S25 enhances the efficacy of several antibiotics against resistant Gram-negative bacteria by disrupting their membranes, thereby increasing drug uptake. This suggests that bacterial membranes are promising targets for new antibiotic adjuvants.
Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins
June 2, 2020
This article relates to the study "Glucose availability dictates the export of the soluble and prion forms of Sup35p via periplasmic or extracellular vesicles" by Kabani et al. (Mol Microbiol, 2020) that provides compelling evidence that yeast prions, such as Sup35p in its infectious [PSI⁺] state, can be exported via both extracellular vesicles (EVs) and periplasmic vesicles (PVs), with this export being modulated by environmental glucose levels. The discovery that prion particles are released in high amounts through PVs during glucose starvation adds a new dimension to our understanding of prion transmission and opens up fascinating possibilities for exploring vesicle-mediated spread of protein aggregates in neurodegenerative diseases using yeast as a model system.
A novel c-di-GMP signal system regulates biofilm formation in Pseudomonas aeruginosa
April 23, 2020
This article relates to the study "The SiaA/B/C/D signaling network regulates biofilm formation in Pseudomonas aeruginosa" by Chen et al. (EMBO J, 2020) that reveals a novel signaling network encoded by the siaABCD operon in Pseudomonas aeruginosa that regulates biofilm and aggregate formation by controlling the diguanylate cyclase activity of SiaD through phosphorylation-dependent interactions with SiaC, highlighting a potential antimicrobial target.