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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.
An environmental bacterium, Burkholderia pseudomallei causes melioidosis, a fatal infection. A study from NE Thailand identifies that dominant lineages carry specific gene sets enhancing environmental persistence.
Stress exposure shapes survival mechanisms in bacteria. Here, the authors show that individual pneumococcal cells react to stress by competence self-induction, which may propagate to non-competent cells, promoting multilevel heterogeneity and favouring survival.
Through transcriptional and phenotypic profiling, authors show that ribose catabolism by the fungus Candida albicans shapes the metabolic landscape of the intra-abdominal cavity to derepress agr signaling in the bacterium Staphylococcus aureus, driving α-toxin release and synergistic lethality during co-infection.
Most rod-shaped bacteria elongate using a protein complex, the elongasome, that inserts new cell wall material into the cell sidewall. Here, Middlemiss et al. track the movement of individual elongasomes around the circumference of Bacillus subtilis cells, providing evidence for a molecular motor tug-of-war competition between oppositely oriented cell-wall synthesis complexes.
The function of many bacterial processes depends on the formation of functional membrane microdomains (FMMs), which resemble the lipid rafts of eukaryotic cells. Here, Ukleja et al. show that FMMs mediate ATP-independent stabilization of unfolded proteins, which is essential for bacterial viability under cellular stress and during infection.
The occurrence of aerobic methane-oxidizing bacteria in anoxic environments is puzzling, as oxygen is thought to be required for methane oxidation. Here, Schorn et al. show that the methane assimilation activity of these bacteria is similar under hypoxic and anoxic conditions in a stratified lake, and the bacteria use fermentation-based methanotrophy as well as denitrification under anoxic conditions.
Several groups of archaea, such as the order Methanocellales, are characterised by their ability to produce methane. Here, Suzuki et al. identify a Methanocellales archaeon that lacks essential methanogenesis genes and seems to be instead a CO2-reducing, electron-fueled acetogen.
Devices based on microbial biofilms can be used to generate hydrovoltaic energy from water evaporation. Here, Ren et al. show that, in addition, electroautotrophic bacteria can use evaporation-induced hydrovoltaic electrons for growth in biofilms.
Eukaryotic Argonaute proteins participate in RNA-guided RNA silencing pathways and are divided into AGO and PIWI clades, with functional and mechanistic differences. Here, the authors show that a deep-branching PIWI protein from Asgard archaea (the closest prokaryotic relatives of eukaryotes) displays hybrid features and may reflect an ancestral molecular architecture that preceded the divergence of eukaryotic AGOs and PIWIs.
This study on a multi-drug resistant infection case shows that real-time genomics can detect low-abundance plasmid-encoded resistance missed by established diagnostics.
Most studies on HIV-1 proviruses that persist during antiretroviral therapy have focused on males with HIV-1 subtype B, even though the majority of people living with HIV globally have non-B subtypes. Here, the authors describe the proviral genetic landscape of HIV-1 subtypes A1 and D in Ugandan females and males using near-full-length proviral sequencing. The authors also describe a molecular assay for intact proviral quantification of these HIV-1 subtypes.
Koenig et al. describe two Campylobacter small RNAs (FlmE and FlmR) that are co-regulated within the flagellar transcriptional cascade and together post-transcriptionally fine-tune expression of components during flagellar biogenesis.
Influenza A viruses pose a continuing pandemic threat to humans. Le Sage, et al. describe a pandemic triage pipeline to evaluate the pandemic risk of emerging viruses and utilize it to characterize two widespread swine influenza A viruses.
Developing broad antiviral drugs against dengue is challenging due to genetic diversity. Here, the authors generate PROTACs targeting the dengue virus envelope protein demonstrating improved potency and broadened activity against other mosquito-borne flaviviruses as compared to the parental inhibitors.
In this study, by analysing immune biomarkers in a cohort of people with advanced HIV, the authors show that elevated levels of some biomarkers at baseline were associated with either increased (CRP, IFN-ƴ, IL-6 and IP-10) or decreased (IL-23, IL-2 and RANTES) likelihood of all-cause mortality.
Here the authors measure viral load in samples from skin lesions, saliva, oropharynx, and rectum of 77 patients with acute monkeypox virus infection as well as from environmental fomite swabs and show a high seropositivity rate for antibodies against A29L and H3L.
Here, the authors analyze the blood transcriptome of Kenyan children with severe malarial anemia and observe impaired immune responses and molecular activation of hypoxia and reactive oxygen species networks, providing insight into disease pathogenesis.
Compound MMV006833 inhibits ring-stage development of Plasmodium falciparum. Here, the authors show that it targets lipid transfer enzyme PfSTART1 and prevents PfSTART1 from expanding the vacuole membrane encasing the parasite after red blood cell invasion, thereby blocking parasite growth.
This study reports the genomics- and metabolomics-guided discovery of aminovinyl-(methyl-)cysteine-containing peptides (ACyP). One of these peptides, massatide A, demonstrates excellent activity against drug-resistant gram-positive pathogens.
In this work, authors combine high resolution imaging and machine learning to infer drug susceptibility in the absence of antimicrobial exposure, with the goal of their method to be transposed to diagnostics and study of the impact of any perturbation on bacterial cells.
Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating widely in birds and have recently caused large outbreaks in mammals. Here, Furey et al. develop a clade 2.3.4.4b HA-expressing mRNA-LNP vaccine and show that it elicits strong protective immune responses in mice and ferrets.
The role of IFN signaling in SARS-CoV-2 infection and outcome is still debated. Here, the authors longitudinally profiled plasma samples from hospitalized patients and show that a persistent inflammatory response is linked to delayed generation of adaptive immunity and increased risk of death when coupled with severe infection.
Antifungal azoles inhibit ergosterol biosynthesis, but how that leads to fungistatic or fungicidal activities in many pathogenic fungi is poorly understood. Here, Schuster, Kilaru & Steinberg show that azole lethality in the plant pathogens Zymoseptoria tritici and Magnaporthe oryzae is due to a combination of reactive oxygen species-induced apoptosis and macroautophagy.
Aerobic methanotrophic bacteria are considered strict aerobes but are often highly abundant in hypoxic or anoxic environments. Here, the authors show that acidophilic methanotrophs can respire nitrous oxide and grow anaerobically on diverse non-methane substrates, including methanol, C-C substrates, and hydrogen.
Mycoviruses are obligate parasites of fungi. Here, Hai et al. show that mycoviruses can induce hypovirulence in the fungus Sclerotinia, and plants infected by Sclerotinia facilitate the transmission of these mycoviruses, thereby helping the plants defend against Sclerotinia.
Despite effective antiviral drugs, HIV-1 transcripts can be found in extracellular vesicles (EVs) in people living with HIV-1. Comparing EVs from serum and cerebrospinal fluid (CSF), the authors show compartmentalized defective viral transcripts that are enriched in the CSF and corelate with cognitive dysfunction.
In this randomized, controlled integrated phase 1/2/3a/3b clinical trial, the authors show that the self-amplifying mRNA COVID-19 vaccine ARCT-154 shows good immunogenicity and is safe and efficient against COVID-19 (57% against any COVID-19, and 95% against severe COVID-19).
Standard diagnostics are often not able to fully capture submicroscopic parasite dynamics after treatment with antimalarials. In this longitudinal analysis of molecular markers of malaria parasitemia in an Ugandan cohort, authors describe persistence of markers following antimalarial therapy with dynamic and complex multiclonal infections in the initial and post-treatment periods.
Little is known about how archaeal viruses counteract host immunity. Here, the authors leverage a viral gene regulatory feature to predict 354 potential anti-defense genes and experimentally validate a CRISPR-Cas I-A inhibitor and an inhibitor of a toxin-antitoxin system.
Exponential growth of toxigenic Streptococcus pyogenes M1UK lineage accounted for most of the 2022/2023 invasive infection upsurge in the UK. Authors provide evidence that M1UK first emerged in 2008, has genetic evidence of enhanced fitness, and has disseminated to 3 continents.
High levels of extended spectrum beta-lactamase (ESBL) and carbapenemase encoding genes were detected in bacterial isolates causing neonatal sepsis in LMICs. Authors assess the in vitro activity of three antibiotics (fosfomycin, flomoxef and amikacin) in combination against ESBL-producing Klebsiella pneumoniae and Escherichia coli isolates.
This is the first report on a virus infecting the amoeboflagellate Naegleria, including the lethal human pathogen N. fowleri. The new virus isolate, Catovirus naegleriensis (Naegleriavirus, NiV), shows hallmarks of giant viruses (Nucleocytoviricota) and unique adaptations to its protist host.
This study presents a machine learning model that accurately predicts seasonal antigenic changes of influenza A H3N2 using genetic data. The model’s predictions can aid influenza surveillance, vaccine strain selection, and public health management.
Antifungal triazoles inhibit biosynthesis of ergosterol, a crucial component of the fungal plasma membrane. Here, Xie et al. show that Erg6, the enzyme that catalyzes a previous step in ergosterol biosynthesis, is essential for the viability of Aspergillus fumigatus, and its repression reduces the virulence of this fungal pathogen in an animal model of infection.
Atmospheric methane-oxidizing bacteria constitute the sole biological sink for atmospheric methane. Here, Schmider et al. assess the ability and strategies of seven methanotrophic species to grow with air as sole energy, carbon, and nitrogen source, showing that these bacteria can grow on the trace concentrations of methane, carbon monoxide, and hydrogen present in air.
Bacterial viruses (phages) are promising alternatives to treat antibiotic-resistant bacterial infections, but finding matching phages against bacteria of interest is challenging. Here, Boeckaerts et al. present a machine learning approach that predicts phage-bacteria pairs at the strain level for Klebsiella pathogens.
The predatory bacterium Bdellovibrio exovorus attaches on the surface on other bacteria and feeds on them. Here, the authors study the lifecycle of B. exovorus, showing that it proliferates by non-binary division, firm junctions are established between prey and predator outer membranes, and a proteinaceous S-layer does not protect prey cells against predation.
SAR11 bacteria and their phages are abundant in the oceans. Here the authors quantify the number of phage-infected SAR11 cells using microscopy techniques and discover phage-infected cells without any detectable ribosomes. They hypothesize that ribosomal RNA may be used for the synthesis of phage genomes.
Here the authors report baseline results of a population-based trial testing concomitant human papillomavirus (HPV) vaccination and HPV-based screening of young women in Sweden and, using a transmission model, suggest that this approach may reduce high-risk HPV infections.
In this study, the authors report the case of a patient who underwent lung transplantation and subsequently developed COVID-19 that resulted in persistent infection. Following antiviral treatment, SARS-CoV-2 (BA.5) showed dynamic genetic diversity with remdesivir resistant mutations leading to enhanced fusogenicity.
Diverse bacteria can use the low levels of hydrogen and carbon monoxide present in the air as energy sources for growth and survival. Here, Leung et al. show that ability is also found in thermophilic archaea of the order Sulfolobales.
Some phages use plasmid-encoded conjugation proteins as receptors to infect their bacterial hosts, making their host range dependent on horizontal transfer of the plasmid. Here, the authors present a method for identification of new plasmid-dependent phages, and find that they are common and abundant in wastewater and their genetic diversity is largely unexplored.
Streptococcus dysgalactiae subsp. equisimilis is closely related to Streptococcus pyogenes and colonises the same sites in humans. This study examines cross-species transmission interactions and genetic exchange in a high disease burden setting.
Mutations in mexZ, encoding a negative regulator of efflux pump genes, are frequently acquired by Pseudomonas aeruginosa during early lung infection, but do not confer high antibiotic resistance as measured in lab tests. Here, Laborda et al. show that mexZ mutations affect quorum sensing pathways, thus promoting tissue invasiveness and protecting bacteria from the action of antibiotics within tissues.
Coccidioidomycosis, a WHO-listed mycosis, is neglected in South America. Analysis of 292 cases in Brazil, often tied to armadillo hunting, unveils unique disease patterns, environmental factors and pathogen genetics causing the disease.
The 2023 monkeypox outbreak was caused by a subclade IIb monkeypox virus (MPXV). Here, using advanced sequencing techniques, the authors identify variations on low-complexity regions of the MPXV genome and describe their potential as evolutionary drivers.
Here, Drury et al study gene, microRNA and protein expression during COVID-19, in a randomised controlled trial of ChAdOx1 nCoV19 vaccine and find that ChAdOx1 nCoV-19 attenuates the inflammatory response, thought to be the basis for severe COVID-19.
In this study, the authors assessed influenza-specific antibody responses in a cohort of seasonally vaccinated children and report that seasonal vaccination is beneficial by enhancing pandemic influenza virus-specific antibodies and cross-reactive effector functions.
Host factors required for parechovirus entry are not well understood. Here, the authors identify MYADM as an essential host entry factor that directly binds human parechovirus 1 and that is required for PeV-A infection in cell lines and human gastrointestinal epithelial organoids.
In hospitals, surfaces present as a reservoir for bacteria pathogens, potentially leading to nosocomial infections. In this work, authors aim to profile extended-spectrum β lactamase- and carbapenemase-carrying bacterial species colonising neonatal hospital wards and causing neonatal sepsis.
Chitwood et al. report on the rapid expansion of a Ural-lineage multidrug resistant strain of Mycobacterium tuberculosis in Moldova. This strain has an estimated reproduction number more than two times greater than otherwise similar drug susceptible strains.
Rise of new viral strains is a major public health challenge, demanding advanced detection and forecasting methods. This study shows how examining communities within networks of viral mutations enables early detection of emerging strains.
Routine sampling of pregnant women at first antenatal care (ANC) visits could be used for malaria surveillance. Here, the authors compare the genetic structure of Plasmodium falciparum parasite populations between samples from first ANC users and children from the community in Mozambique, and show that it can inform about changes in transmission beyond epidemiological data.
Co-infections are much less studied than single pathogen infections. Here, the authors show that co-infection with two unrelated viruses, neurotropic Semliki Forest virus and influenza A virus, exacerbates influenza-related lung pathology and prolongs lung virus replication in a mouse model.
There is limited data on immune factors contributing to SARS-CoV-2 viral clearance in people living with HIV. Here, the authors show that re-emergence of the neutralizing antibody response may be key to clearing persistent SARS-CoV-2 infection in ART-mediated recovery from immunosuppression in advanced HIV disease.
Sturm et. al developed a 2 to 4 h antibiotic susceptibility test based on bacterial vibrations. This diagnostic test applies to the most frequently found gram-negative bacteria in bloodstream infections and demonstrates its potential in contributing to faster treatment decisions.
Catheter-associated urinary tract infections can often lead to secondary bloodstream infections, and catheter-induced bladder inflammation. In this work, authors utilise murine models to probe defective fibrinolysis drives extravascular fibrin formation, potentially predisposing hosts to severe CAUTI.
In this work, authors combine computational models with single-cell and population-level data showing the variability in plasmid copy number within bacterial populations leads to phenotypic diversity. They reveal how multicopy plasmids contribute to bacterial transient antibiotic resistance.
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.
Cerebral malaria can lead to fatal brain swelling. Oelschlegel et al. find infected red blood cells and reduced flow in large draining cerebral veins in mouse model of cerebral malaria, suggesting that impaired venous efflux could cause the swelling.
Phage-plasmids are mobile genetic elements that transfer horizontally between bacterial cells as viruses, and vertically within bacterial lineages as plasmids. Here, Pfeifer & Rocha show that phage-plasmids can mediate gene transfer across mobile elements within their hosts, and can act as intermediates in the conversion of one type of element into another.
The second messenger c-di-GMP regulates various processes in bacteria, including biofilm formation and motility. Here, the authors show that iron regulates c-di-GMP levels in Pseudomonas aeruginosa by modulating the interaction between an iron-sensing protein and a diguanylate cyclase.
Bacteria form matrix-encapsulated communities, called biofilms, which protect resident cells from environmental challenges. Here, the authors show that Vibrio cholerae cells detect environmental threats by sensing a cellular component released through kin cell lysis, which induces formation of biofilms by surviving cells.
Here the authors study recovery from mild to moderate Omicron breakthrough infection at six months post infection. Serum proteomics, PBMC single-cell transcriptomics and clinical parameters indicate slow recovery with coagulation abnormalities and an imbalance of the immune response and metabolism remaining.
Here the authors describe a stabilization technology that engineers crosslinks between tyrosine sidechains into a natively folded vaccine immunogen and show that immunogenicity is improved in small animal models by locking the most potently neutralizing epitopes.
SARS-CoV-2 uses the host endolysosomal system for replication and egress. Here the authors show that SARS-CoV-2 virulence factor ORF3a localizes to the late endocytic compartments of the host cell to disrupt Rab7 GTP to GDP cycling and block lysosome function in cargo degradation, while activated Rab7 promotes virus replication.
Bacterial capsules provide protection against the environment, including host immune systems. Authors swap capsule loci in Klebsiella pneumoniae to reveal the role of these sugar coats against plasmid conjugation and phage infection, showing that the serotype is a key player in regulating conjugation rates, and phage susceptibility.