Pathogens articles within Nature Communications

Plasmodium sporozoites actively migrate in the dermis and enter blood vessels to induce infection. Here, Formaglio et al. show that Plasmodium sporozoites alternate global superdiffusive skin exploration and local subdiffusive blood vessel exploitation to find intravasation hotspots associated with pericytes, enter the blood circulation and start malaria infection.

Macrophages have the inherent capacity to recognise pathogenic microorganisms, highlighting their potential to be used in biosensing applications. Herein, the authors report a method to transform normally fragile macrophages into robust gelated cell particles for efficient bacterial capture and detection.

Serine/threonine kinases (STKs) regulate the synthesis of capsular polysaccharide in bacteria through unclear mechanisms. Here, Tang et al. identify a protein that is phosphorylated by an STK and modulates the activity of a phosphoregulatory system in Streptococcus suis, thus linking STKs to capsular polysaccharide synthesis.

Infection with Streptococcus pyogenes after childbirth can have life threatening consequences. Here, Catton et al. show that the epidemiologically associated bacterial R28 protein targets the human CEACAM1 receptor to facilitate the pathogenesis of bacterial sepsis.

Bacterial cell growth and division require the coordinated action of enzymes that synthesize and degrade cell wall polymers. Here, the authors identify enzymes that cleave the D-arabinan core of arabinogalactan, an unusual component of the cell wall of Mycobacterium tuberculosis and other mycobacteria.

Bacteria often express multiple adhesive proteins (adhesins) for biofilm formation, but it is often unclear whether adhesins have specialized or redundant roles. Here, the authors show that Vibrio cholerae uses two adhesins with overlapping but distinct functions to achieve robust adhesion to diverse surfaces.

High morbidity and mortality in aquatic have been caused by iridovirids worldwide. Here the authors present a near-atomic SGIV capsid structure. Functional assays further reveal the relationships between identified capsid proteins and viral assembly.

The pathogenic fungus Candida albicans can switch between a mating-competent form (“opaque” cells) and a form that is thought to be essentially sterile (“white” cells). Here, the authors show that glucose depletion, a common nutrient stress, enables C. albicans white cells to undergo efficient sexual mating.

Geographical hotspots with high frequency of multi-drug resistant tuberculosis (MDR-TB) have been observed in several locations, such as the country of Georgia. Here, the authors analyse genomic sequences from tuberculosis bacteria isolated from Georgia to show that the transmission fitness of MDR-TB strains is heterogeneous, and highly drug-resistant and transmissible isolates contribute to the emergence and maintenance of MDR-TB hotspots.

In this work, the authors developed a multiplexed, minimally invasive, CRISPR-Cas13-based approach to detect Mycobacterium tuberculosis cell-free DNA in the plasma of active pulmonary tuberculosis patients.

In this work, the authors induce ciprofloxacin resistance in clinical isolates of Pseudomonas aeruginosa to investigate transient collateral sensitivity to tobramycin.

The complement system is a key protective response against infectious pathogens. Here, the authors show that Helicobacter pylori uses host L-lactate to generate a complement resistant state that promotes gastric colonisation.

Drug resistance to current antimalarials is rising and new drugs and targets are urgently needed. Here the authors identify Plasmodium falciparum acyl-CoA synthetase 10 as a new target whose inhibition leads to a decrease in triacylglycerols.

Arboviruses and symbiotic viruses can be paternally transmitted by male insects to their offspring, but the mechanism remains largely unknown. Here, the authors identify the sperm-specific serpin protein HongrES1 of the leafhopper Recilia dorsalis as a mediator of paternal transmission of the reovirus rice gall dwarf virus and of a previously undescribed symbiotic virus of the Virgaviridae family, Recilia dorsalis filamentous virus, via direct binding of virions to leafhopper sperm surfaces and subsequent paternal transmission via interaction with both viral capsid proteins.

Salmonella typhimurium translocates numerous effectors via its type III secretion system. Here, Göser et al. present a characterisation of selected proteins and their dynamic interaction with Salmonella-containing vacuoles and – induced filaments.

A variant of group A Streptococcus serotype M1 (UK) has been increasingly reported and can be differentiated from the global variant by its overexpression of the superantigen SpeA. Here, Davies et al probe the mechanism behind enhanced SpeA expression and demonstrate that a SNP in the 5’ leader sequence of ssrA is responsible for this virulence phenotype.

Pathogenic Brucella abortus, containing a mix of lipopolysaccharides with or without O-antigen, grows its envelope in a unipolar manner. Here, Servais et al, localize the LPS translocation machinery and identify the main O-antigen ligase in Brucella species, shedding light on the basic biology of this organism.

Bacteria can affect cellular processes in other bacteria and in eukaryotic cells by injecting effectors using a type VI secretion system (T6SS). Here, Sá-Pessoa et al. describe how a T6SS effector from the bacterial pathogen Klebsiella pneumoniae triggers the fragmentation of the mitochondrial network in eukaryotic cells.

Here, the authors characterise Acinetobacter baumanii and Klebsiella pneumoniae isolated from a single human lung infection and proceed to define their interactions to shed light on how this impacts their evolution, growth parameters, metabolism and antimicrobial responses.

Barrier-to-autointegration factor 1 (BAF) is a DNA binding protein involved in numerous pathways including transcriptional regulation, DNA damage response and nuclear assembly. Here, Broussard and colleagues characterise its role in gammaherpesvirus reactivation.

Cagβ is an ATPase in the H. pylori CagType4 secretion system essential for delivering the CagA effector to host cells. Here, authors present crystal structures of hexameric apo-Cagβ and Cagβ trapped in the monomeric state by its regulator CagZ, uncovering the regulatory mechanisms of Cagβ.

Biological processes can be regulated via oligomerization of macromolecules into high-order symmetric structures. Here, authors reported high-order structure of RNA polymerase and its role in regulation of gene expression in pathogenic bacterium.

Here, using Citrobacter rodentium colonization of mice as a model, the authors characterize the impact of pathogen dose on the number of bacteria that initiate infection in the mouse gut, providing a framework for quantifying the host bottlenecks that eliminate pathogens to protect from infection.

The alternative sigma factor RpoS of Borrelia burgdorferi regulates a pathway implicated in tick transmission, mammalian infectivity and persistent infection. Here, the authors characterise the role of the RpoS negative regulator bbd18 and show that RpoS also controls induction of endogenous prophage.

The bacterium Brucella abortus is an intracellular pathogen that modulates autophagy in host cells. Here, the authors identify two B. abortus effectors that interact with host protease SENP3, thus promoting cytoplasmic accumulation of nucleolar proteins associated with ribosomal biogenesis and facilitating intracellular replication of the pathogen

The multifunctional GSDMB protein is an important molecule in human immunity. Here, the authors decipher the molecular mechanisms of GSDMB targeting by the bacterial virulence factor IpaH7.8 and provide insights into GSDMB-mediated pyroptosis.

Some bacteria use the muropeptide transporter AmpG for uptake and recycling of cell wall fragments that are released during cell growth and division. Here, Gilmore & Cava show that the plant pathogen Agrobacterium tumefaciens, which lacks an AmpG homologue, uses a different type of transporter for the same function, which is essential for normal growth in this organism.

Pathogenic fungi of the genus Cryptococcus can undergo bisexual and unisexual reproduction. Here, the authors construct a gene-deletion library for over 100 transcription factor genes in Cryptococcus deneoformans and provide insights into regulatory cascades that are specific for each reproductive mode.

The bacterium Salmonella Paratyphi A causes paratyphoid fever. Here, the authors sequence over 800 isolates from South Asia, build a global database representing 37 countries, and develop a genotyping tool that identifies genomic variation and antimicrobial resistance markers for surveillance studies.

The streptococcal enzymes IdeS and EndoS cleave IgG antibodies with exquisite substrate specificity, which has enabled their development as clinical and biotechnological tools. Here, the authors present crystal structures of both enzymes in complex with their IgG1 Fc substrate.

Vancomycin-resistant Enterococcus (VRE) represents a major threat for patients’ health. Here, using a mouse model, the authors show that specific commensals restrict VRE gut colonization through depletion of fructose, a nutrient source that boosts VRE growth in vivo.

Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction, however, the molecular pathways resulting in endothelial barrier dysfunction and vascular leakage are only sparsely understood. Here, Biering et al. show that SARS-CoV-2 spike protein is sufficient to induce barrier dysfunction and vascular leak. They show a role for integrins, TGF-beta, ECM remodeling enzymes, and glycosaminoglycans in this S-mediated barrier dysfunction.

The pathogen Pseudomonas aeruginosa uses a synthase-dependent secretion system for production of the exopolysaccharide alginate, which is associated with lung infection severity. Here, Gheorghita et al. determine the crystal structure of one of the secretion system components (the AlgKX complex) and show that it binds alginate oligosaccharides and is required for polymer production and biofilm attachment.

Small regulatory RNAs (sRNAs) often act in concert with the RNA-chaperone Hfq to regulate the expression of multiple target transcripts in bacteria. Here, the authors identify Hfq-interacting sRNAs and their targets in the pathogen Vibrio cholerae, including an RNA sponge that binds and inactivates four sRNAs that modulate the quorum sensing pathway.

Opportunistic bacterial pathogen species frequently colonise the human gut as a normal part of the ecosystem but strain-level colonisation and competition dynamics in healthy hosts is yet to be established. Authors seek to understand the relationship between colonisation potential and ecological factors modulating pathogen prevalence in disease in a longitudinal cohort.

Interplay of enzyme PqsE and transcription factor RhlR controls the virulence of Pseudomonas aeruginosa. Here, the authors show that complex formation with PqsE stabilizes RhlR in a soluble active state. PqsE/RhlR complex structures provide a basis for drug discovery against this important pathogen.\

There is increasing evidence for metabolic processes mediating antimicrobial resistance. Here, the authors present a mechanism of sulfamethoxazole resistance in Group A Streptococcus that is dependent on acquiring end products of the host folate biosynthesis pathway.

Staphylococcus aureus is increasingly recognized as a facultative intracellular pathogen, but it is unclear whether the intracellular lifestyle is a general feature or is restricted to some isolates. Here, Rodrigues Lopes et al. profile the interaction of 191 clinical isolates with four host cell types over time, showing that almost all isolates are internalized and that a large fraction replicate and persist within host cells.

The bacterium Borrelia burgdorferi, which causes Lyme disease and is transmitted by ticks, has a linear chromosome and multiple plasmids. Here, Takacs et al. show that the pathogen is polyploid, the number of genome copies decreases during stationary phase, and chromosome copies are regularly spaced along the cell’s length.

Decreased functionality and expression of trypanosome haptoglobin-hemoglobin receptor (HpHbR) is one of the evolutionary modifications that have allowed Trypanosoma brucei gambiense to infect humans. Here, Horakova et al. show that hemoglobin uptake in African trypanosomes is mediated almost exclusively by HpHbR and relevant for slender-to-stumpy differentiation. T. b. gambiense is poorly competent to differentiate into stumpy forms compared to T. b. brucei, due to reduced functionality of HpHbR.

H37Rv is the most widely used Mycobacterium tuberculosis strain, and its genome is the reference sequence for this pathogen. Here, Chitale et al. present a bioinformatic pipeline for accurate assembly of bacterial genome sequences, and use it to provide important updates to the M. tuberculosis reference genome.

A number of human African trypanosomiasis, or sleeping sickness, patients suffer from respiratory symptoms commonly attributed to cardiac insufficiency. Here, the authors characterise the role of pulmonary Trypanosoma brucei in respiratory infection.

Proteasomes are vital eukaryotic complexes that recycle unneeded proteins. Here, the authors present the structure of a compacted proteasome derived from the dormant stage of parasitic microsporidia and bound by an endogenous inhibitory protein.

Here, the authors perform large-scale high-resolution Parkinson’s disease metagenomics analyses, revealing widespread dysbiosis characterized by overabundance of pathogens, immunogens, toxicants, and curli, reduction in neuroprotective and antiinflammatory molecules, and dysregulated neuroactive signaling.

Poxins or P26 have been identified as inhibitors of cGAS-STING mediated innate immunity. Here, the authors describe an independently evolved antiviral function of P26 in suppressing melanization, an insect immune response.

Toxin B (TcdB) is a major exotoxin responsible for diseases associated with C. difficile infection. Here, Tian et al. show that several TcdB subtypes do not recognize the established FZD receptors, and identify a different host protein (TFPI) as a receptor for subtypes TcdB4 and TcdB10.

Cyclic-di-GMP transduces extracellular stimuli into intracellular responses to modulate important biological processes. Here, the authors show that AI-2 and bile salts induce cyclic-di-GMP synthesis via YeaJ and YedQ, respectively, to repress the T3SS via a cyclic-di-GMP-responsive T3SS chaperone.

The pathogenic yeast Cryptococcus neoformans forms large, so-called ‘titan cells’ during infection. Here, Cao et al. show that a ubiquitin ligase inhibits this process by targeting for degradation a CDK-related kinase that stimulates titan cell formation.

The response regulator SsrB, a master activator of the Salmonella pathogenicity island-2 gene cluster, is under allosteric control of thioredoxin. Authors utilise in vitro and in vivo models to investigate if other members of the response regulator family might have adopted thioredoxin as a regulator.