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The study of microorganisms, the most abundant living entities on Earth, aims to understand their unique biology and the influence they have on human health, disease, and life in general. Here, we highlight work that furthers our understanding of the microbial world.
In this work, authors utilise a pan-resistant Pseudomonas aeruginosa in vivo infection model to demonstrate antibiotic re-sensitisation with bacteriophage therapy.
Stupar et al. describe a new role for the Mycobacterium tuberculosis two-component system, TcrXY, in the modulation of up to 70 genes, including two effectors, TarA and TarB which mitigate intracellular redox stress.
Authors present a comparative immunological characterisation of Chlamydia vaccine, CTH522/CAF®01, in mice and humans. Findings suggest the mouse to be a good predictor of human immunity to the Chlamydia vaccine CTH522/CAF®01, and long-lasting protection in the mouse further supports the development of this promising vaccine candidate.
Key cellular processes, such as cell-shape determination, are poorly understood in archaea. Here, Schiller et al. study the model archaeon Haloferax volcanii, which forms rods and disks, and identify a diverse set of proteins important for these processes, including a new actin homolog that plays a role in the formation of disk-shaped cells.
The cell-wall peptidoglycan in model bacteria typically includes 4,3- and 3,3-crosslinks, catalysed by DD- and LD-transpeptidases, respectively. Here, the authors identify and characterise the activity and structure of an LD-transpeptidase that generates a new type of crosslink (1,3).
Genomic surveillance of Plasmodium falciparum could improve monitoring of drug resistance, but implementation has been hampered due to the large and complex genome. Here, de Cesare et al. develop a flexible and cost-effective nanopore sequencing approach to detect drug resistance and diagnostic escape for P. falciparum malaria.
Flavivirus infection or vaccination can induce cross-reactive immune responses. Here, the authors show how previous immunization with the tick-borne encephalitis virus vaccine affects the immune response to the yellow fever vaccine, suggesting that the yellow fever vaccine virus conceals epitopes shared with other flaviviruses in flavivirus-naive but not flavivirus-pre-exposed individuals.
The Wolbachia cifA and cifB genes generate cytoplasmic incompatibility (CI) in insect hosts but the role of cifA is still debated. Here, the authors report the transgenic recapitulation of CI in the major arbovirus vector Aedes aegypti and provide evidence for cifA inhibiting cifB toxicity in the male germline.
Here, the authors provide evidence that, unlike other arboviruses, the initial site of orthobunyavirus replication is the panniculus carnosus muscle layer within the skin. However, virus infection does not damage or kill these cells, allowing them to produce virus over a longer period of time.
Bacteria use various defense systems to protect themselves from phage infection, and phages have evolved diverse counter-defense measures to overcome host defenses. Here, the authors use protein structural similarity and gene co-occurrence analyses for identification of new anti-phage and counter-defense systems.
Previous reports of microbial endemism have been restricted to sub-genus level taxa. Here, Power et al. present evidence supporting that a bacterial genus, Venenivibrio, is endemic to Aotearoa-New Zealand.
Treatment with the clinical stage TGF-β inhibitor galunisertib promotes latency reversal of HIV/SIV. Here, using a treatment regimen similar to the one tested in clinical trials, the authors show how galunisertib affects immune cell function, increases SIV reactivation, and reduces the viral reservoir in macaques.
Measles virus infection causes immunosuppression and it’s unclear whether this can be prevented by antivirals. Here, using a canine distemper virus ferret model, the authors show that measles-like immune amnesia and lethal exacerbated respiratory disease after consecutive respiratory virus infections can be mitigated by oral antiviral therapy initiated at the onset of primary clinical signs.
Bacterial viruses (phages) are generally recognised as rapidly evolving biological entities. Here, Rozwalak et al. analyse DNA sequence datasets generated from ancient palaeofaeces and identify 298 phage genomes from the last 5300 years, including a 1300-year-old phage genome nearly identical to a present-day virus that infects human gut bacteria.
In vitro propagation of the pathogenic bacterium Coxiella burnetii, the causative agent of Q fever, leads to attenuated virulence and lipopolysaccharide (LPS) truncation. Here, Long et al. show that a strain considered to be avirulent (NMII) can be recovered from infected animals, and these isolates display increased virulence and an elongated LPS due to reversion of a 3-bp mutation in a gene.
Cheese fermentation and flavour formation are the result of complex biochemical reactions driven by the activity of multiple microorganisms. Here, the authors identify microbial interactions as a mechanism underlying flavour formation in Cheddar cheese.
Authors apply theory and microbial ecology modelling to a wastewater sample, and show that antimicrobial resistance carrying plasmids interact with a higher number and more diverse range of bacteria than plasmids that do not carry resistance genes.
In this work, the authors identified a hypervirulent carbapenem-resistant Escherichia coli ST410 clone which carries a high pathogenicity island and an O-antigen gene cluster. The findings highlight the ongoing evolution of ST410 towards increased resistance and virulence.
Here the authors screen different lipid nanoparticle (LNP) formulations for intramuscular delivery of plasmid DNA and uptake by antigen-presenting cells. The lead LNP exhibits immunogenicity and protection in small animal models that is comparable to approved SARS-CoV-2 mRNA vaccine formulations.
Wang et al. discovered that AP2XI-2 and AP2XII-1 negatively regulate merozoite-primed pre-sexual commitment in Toxoplasma gondii, and parasites depleted of either AP2XI-2 or AP2XII-1 can serve as a valuable in vitro model for studying merogony.
Here, the authors uncover that, among 92 identified host factors associated with SARS-CoV-2 virions, G3BP1 and G3BP2 are present at the assembly site, incorporated within virions, and unexpectedly promote the production of SARS-CoV-2 virions.
Using unique single mosquito data the authors revisit the core quantitative relationships between sequential stages of Plasmodium parasites in their vector host. Their findings demonstrate the importance of mosquito parasite burden in onward transmission success.
The ecology of Ebola virus (EBOV) is still largely unclear. Here, the authors show that Angolan freetailed bats are selectively permissive to EBOV infection, but not to other filoviruses, and demonstrate EBOV placental tissue tropism indicating potential horizontal and vertical transmission between conspecifics.
What a microbial strain is and how many strains make up a natural bacterial population remain elusive concepts. Here, Viver et al. analyse Salinibacter ruber isolates and metagenomes from two solar salterns, revealing gaps within the species sequence space that they use to define and quantify sub-species categories, such as genomovars and strains, that co-exist in a saltern pond.
The type VI secretion system (T6SS) of Gram-negative bacteria is typically anchored to the cell envelope through a membrane complex (MC), but Bacteroidota appear to lack genes encoding canonical MC components. Here, Bongiovanni et al. identify the Bacteroidota MC and study its biogenesis and connections with the conserved T6SS components.
A defining feature of retroviruses compared to other +ssRNA viruses is reverse transcription. Here, Köppke et al. show that retroviruses (e.g. HIV-1) can produce viral proteins even in the absence of reverse transcription.
Cryo-EM structures of the polymerase of Tilapia Lake virus (Amnoonviridae), a fish pathogen, show that it has the same domains and functions similarly to the distantly related influenza virus (Orthomyxoviridae) polymerase, despite being only 60% the size.
The archaeal ancestor of eukaryotes belonged to the phylum Asgardarchaeota, or Asgard archaea. Here, the authors use ancestral sequence reconstruction and experimentally determine the optimal GDP-binding temperature of a translation elongation factor from ancient and extant Asgard archaea, to infer optimal growth temperatures for eukaryotes’ ancestors.
Molecular diagnostics for tuberculosis have focused on predicting drug susceptibilities in a binary manner (i.e., strains are either susceptible or resistant). Here, CRyPTIC Consortium researchers use whole genome sequencing and a quantitative assay to identify associations between genomic mutations and minimum inhibitory concentrations in over 15,000 Mycobacterium tuberculosis clinical isolates.
The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.
Lower respiratory tract disease is a common complication after allogeneic hematopoietic cell transplant (HCT), but underlying reasons remain unclear. Here the authors show that HHV-6B detection in the lungs of allogeneic HCT recipients is associated with increased risk for death and distinct host gene expression profiles, implicating HHV-6B as a pulmonary pathogen in these patients.
The authors examine temporal polymicrobial community composition in patients with long-term urinary catheters to identify species co-occurrences and demonstrate uropathogenic Escherichia coli augments growth of a prevalent opportunistic uropathogen in urine.
Here the authors report an exploratory analysis of a clinical trial that tested different influenza virus vaccination platforms. The results show that multiple seasons of recombinant or cell-based influenza vaccinations may be needed to redirect antibody responses away from immune memory to egg-adapted epitopes and refocus on epitopes on the circulating viruses.
Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.
The enzymes FtsW and FtsI are thought to be essential for the synthesis of septal peptidoglycan (PG) during bacterial cell division. Here, Shrestha et al. show that the pathogen Clostridioides difficile lacks a canonical FtsW/FtsI pair, with its homologs fulfilling sporulation-specific roles including the synthesis of septal PG during sporulation-specific cell division.
Bacteriophages have primarily been studied using fast-growing laboratory cultures of their bacterial hosts. Here, Maffei et al. show that diverse phages can infect deep-dormant bacteria and suspend their replication until the host resuscitates; however, a particular phage can directly replicate and induce the lysis of deep-dormant hosts.
Aedes aegypti transmit several arboviruses and control of the mosquito populations could be beneficial. Here the authors show that deletion of leucine aminopeptidase1 (LAP1) results in mitochondrial defects and abnormal autophagy in sperm, reducing fertility and fecundity of females. LAP1−/− males show no obvious defects in longevity and mating fitness.
The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences.
Here the authors show that elevated serum levels of deaminated amino acid catabolites involved in de novo nucleotide synthesis pathway correlate with later COVID-19 severity. These elevated levels are likely associated with abnormal proliferation of airway and vascular cells in the lung.
The ability of marine bacteria to direct their movement in response to chemical gradients influences inter-species interactions, nutrient turnover, and ecosystem productivity. Here, Clerc et al. show that marine bacteria are strongly attracted to algal polysaccharides, and this chemotactic behaviour is enhanced by dimethylsulfoniopropionate (DMSP), a ubiquitous algal metabolite.
Coronavirus RNA replication is governed by membrane vesicles containing pores. The authors used in situ cryo-electron tomography to reveal the minimal constituents of a SARS-CoV-2 “replicopore” and its role in the formation of replication vesicles.
This study reveals the recruitment of several cellular enzymes involved in redox and methylation processes, to endoplasmic reticulum membranes remodeled by Zika virus. These proteins regulate stability, folding and modifications of viral proteins or RNA.
E. coli maintains membrane lipid asymmetry by transferring glycerophospholipids from the outer membrane to the inner membrane; this requires outer membrane protein MlaA, periplasmic chaperone MlaC, and inner-membrane complex MlaBDEF. Here, the authors show that in some bacteria that lack MlaA and MlaC, MlaD forms a transenvelope bridge comprising a typical inner-membrane domain and, in addition, an outer-membrane domain.
Research on the biology and pathogenicity of ‘Candidatus Liberibacter asiaticus’ (CLas), the bacterium that causes citrus Huanglongbing disease, is hampered by our inability to cultivate it in artificial media. Here, Carter et al. use a high-throughput yeast-two-hybrid screen to identify thousands of interactions between CLas proteins, thus providing insights into their potential functions.
Bacterial functional diversity does not necessarily correlate with taxonomic diversity because average genome size may vary by community. Here, Wang et al. investigate bacterial communities along a natural pH gradient in forest soils, and find that average genome size and functional diversity decrease, whereas taxonomic diversity increases, as soil pH rises from acid to neutral.
Convergent strains, those containing characteristics of both multidrug-resistant & hypervirulent Klebsiella pneumoniae, are a global threat to public health. In this work, authors analyse convergent isolates from the United States and reveal unexpectantly low virulence.
A global analysis of antimicrobial resistance (AMR) across 27,155 genomes and 69 drugs reveals patterns in AMR gene transfer between species and identifies 142 AMR gene candidates, two of which were tested and confirmed as contributing to AMR.
Simanek et al. discovered variants that arise in the protein responsible for synthesizing a molecule required for bacterial communication, which mediates the progression of virulence in the pathogen Pseudomonas aeruginosa.
As a leading cause of diarrhoeal mortality and morbidity, authors examine the epidemiology and genome dynamics of shigellosis in South Africa, utilising whole genome sequence analysis.
The authors use lipid nanoparticles (LNPs) that predominantly accumulate in the lung to deliver mRNA encoding for the broadly neutralizing antibody 8-9D, and achieve superior inhibition of SARS-CoV-2 infection in mice compared to control LNPs.
Small molecule drugs can affect clearance of monoclonal antibodies, but this hasn’t been assessed for oral HIV-1 pre-exposure prophylaxis. Here, the authors find that faster serum clearance of an experimental IgG1 monoclonal antibody, VRC01, is associated with use of tenofovir-emtricitabine, possibly explained by increased epithelial intestinal permeability.
Parveen et al., using immunological, and metabolomics-based assays, demonstrate the importance of host glutamine metabolism in tuberculosis pathogenesis and show host-directed activity against tuberculosis.
The mechanisms regulating fungal-algal interactions during the formation of lichen symbioses are not clear. Here, Wang et al. establish conditions conducive to symbiotic interactions and lichen differentiation using a fungus amenable to genetic manipulation, showing the importance of a MAP kinase in lichen development.
Bacteria usually have at least one rRNA operon on the chromosome, suggesting that the exclusive presence of rRNA operons on a plasmid is rare and unlikely to be stably maintained. Here, Anda et al. find that at least four bacterial clades in different phyla lost their chromosomal rRNA operons independently, and one of the clades has maintained this peculiar genome organization for hundreds of millions of years.
The Mycobacterium tuberculosis complex (MTBC) includes several pathogens thought to have originated in East Africa from an ancestor closely related to Mycobacterium canettii. Here, the authors describe a clinical tuberculosis strain isolated in Ethiopia that has typical M. canettii features but is phylogenetically much closer to the MTBC clade, supporting that the emergence of MTBC pathogens is a recent evolutionary event.
Proteins are composed of distinct functional domains, each serving a specific role. Here, Smug et al. show that phages are able to shuffle fragments of their proteins and this predominantly occurs in proteins involved in bacterial host interactions.