Diverse Sensory Repertoire of Paralogous Chemoreceptors Tlp2, Tlp3, and Tlp4 in .

Campylobacter jejuni responds to extracellular stimuli via transducer-like chemoreceptors (Tlps). Here, we describe receptor-ligand interactions of a unique paralogue family of dCache_1 (double lcium channels and motaxis) chemoreceptors: Tlp2, Tlp3, and Tlp4. Phylogenetic analysis revealed that Tlp2, Tlp3, and Tlp4 receptors may have arisen through domain duplications, followed by a divergent evolutionary drift, with Tlp3 emerging more recently, and unexpectedly, responded to glycans, as well as multiple organic and amino acids with overlapping specificities.

Structural Basis for Rabbit Hemorrhagic Disease Virus Antibody Specificity.

Rabbit hemorrhagic disease virus (RHDV) typically causes a fatal disease in rabbits. In Australia, RHDV was imported to control the feral rabbit population, while it poses a severe threat to native rabbits in other countries. RHDV variants are genetically diverse and serological studies using antibodies isolated from infected rabbits or raised against RHDV virus-like particles (VLPs) have found RHDV variants antigenically distinct.

Naturally Acquired Kelch13 Mutations in Plasmodium falciparum Strains Modulate Ring-Stage Artemisinin-Based Drug Tolerance and Parasite Survival in Response to Hyperoxia.

The ring-stage survival assay was utilized to assess the impact of physiological hyperoxic stress on dihydroartemisinin (DHA) tolerance for a panel of Plasmodium falciparum strains with and without Kelch13 mutations. Strains without naturally acquired Kelch13 mutations or the postulated genetic background associated with delayed parasite clearance time demonstrated reduced proliferation under hyperoxic conditions in the subsequent proliferation cycle. Dihydroartemisinin tolerance in three isolates with naturally acquired Kelch13 mutations but not two genetically manipulated laboratory strains was modulated by hyperoxic stress exposure of early-ring-stage parasites in the cycle before drug exposure.

N-Linked Glycans Shape Skin Immune Responses during Arthritis and Myositis after Intradermal Infection with Ross River Virus.

Arthritogenic alphaviruses are mosquito-borne arboviruses that include several re-emerging human pathogens, including the chikungunya (CHIKV), Ross River (RRV), Mayaro (MAYV), and o'nyong-nyong (ONNV) virus. Arboviruses are transmitted via a mosquito bite to the skin. Herein, we describe intradermal RRV infection in a mouse model that replicates the arthritis and myositis seen in humans with Ross River virus disease (RRVD).

Repurposing the Ionophore, PBT2, for Treatment of Multidrug-Resistant Neisseria gonorrhoeae Infections.

Multidrug-resistant (MDR) N. gonorrhoeae is a current public health threat. New therapies are urgently needed.

Pneumococcal Phasevarions Control Multiple Virulence Traits, Including Vaccine Candidate Expression.

Streptococcus pneumoniae is the most common cause of bacterial illness worldwide. Current vaccines based on the polysaccharide capsule are only effective against a limited number of the >100 capsular serotypes. A universal vaccine based on conserved protein antigens requires a thorough understanding of gene expression in S.

The Delta SARS-CoV-2 Variant of Concern Induces Distinct Pathogenic Patterns of Respiratory Disease in K18-hACE2 Transgenic Mice Compared to the Ancestral Strain from Wuhan.

Compared to the original ancestral strain of SARS-CoV-2, the Delta variant of concern has shown increased transmissibility and resistance toward COVID-19 vaccines and therapies. However, the pathogenesis of the disease associated with Delta is still not clear. In this study, using K18-hACE2 transgenic mice, we assessed the pathogenicity of the Delta variant by characterizing the immune response following infection.

The Copper Resistome of Group B Streptococcus Reveals Insight into the Genetic Basis of Cellular Survival during Metal Ion Stress.

In bacteria, copper (Cu) can support metabolic processes as an enzymatic cofactor but can also cause cell damage if present in excess, leading to intoxication. In group B Streptococcus (GBS), a system for control of Cu efflux based on the prototypical operon supports survival during Cu stress. In some other bacteria, genetic systems additional to the operon are engaged during Cu stress and also contribute to the management of cellular Cu homeostasis.

Interleukin-17 Contributes to Chikungunya Virus-Induced Disease.

Alphaviral arthritides caused by mosquito-borne arboviruses such as chikungunya virus (CHIKV) can persist for months after the initial acute disease. Here, we investigated the contribution of interleukin-17 (IL-17), a cytokine involved in chronic autoimmune arthropathies such as rheumatoid arthritis, to the development of alphaviral arthropathy. Sera from CHIKV-infected patients who displayed both acute and chronic disease showed high levels of IL-17, IL-6, IL-21, IL-22, and IL-23, especially during the chronic phase of disease.

TIR-Domain-Containing Adapter-Inducing Interferon-β (TRIF)-Dependent Antiviral Responses Protect Mice against Ross River Virus Disease.

Ross River virus (RRV) is the major mosquito-borne virus in the South Pacific region. RRV infections are characterized by arthritic symptoms, which can last from several weeks to months. Type I interferon (IFN), the primary antiviral innate immune response, is able to modulate adaptive immune responses.

Vaccinating Children against COVID-19: Commentary and Mathematical Modeling.

With the recent licensure of mRNA vaccines against COVID-19 in the 5- to 11-year-old age group, the public health impact of a childhood immunization campaign is of interest. Using a mathematical epidemiological model, we project that childhood vaccination carries minimal risk and yields modest public health benefits. These include large relative reductions in child morbidity and mortality, although the absolute reduction is small because these events are rare.

Differential Afa/Dr Fimbriae Expression in the Multidrug-Resistant Escherichia coli ST131 Clone.

Many antibiotic resistant uropathogenic Escherichia coli (UPEC) strains belong to clones defined by their multilocus sequence type (ST), with ST131 being the most dominant. Although we have a good understanding of resistance development to fluoroquinolones and third-generation cephalosporins by ST131, our understanding of the virulence repertoire that has contributed to its global dissemination is limited. Here we show that the genes encoding Afa/Dr fimbriae, a group of adhesins strongly associated with UPEC that cause gestational pyelonephritis and recurrent cystitis, are found in approximately one third of all ST131 strains.

Development and Evaluation of a Cryopreserved Whole-Parasite Vaccine in a Rodent Model of Blood-Stage Malaria.

Infection with malaria parasites continues to be a major global public health issue. While current control measures have enabled a significant decrease in morbidity and mortality over the last 20 years, additional tools will be required if we are to progress toward malaria parasite eradication. Malaria vaccine research has focused on the development of subunit vaccines; however, more recently, interest in whole-parasite vaccines has reignited.

Self-Inhibitory Peptides Targeting the Neisseria gonorrhoeae MtrCDE Efflux Pump Increase Antibiotic Susceptibility.

Neisseria gonorrhoeae is an increasing public health threat due to its rapidly rising incidence and antibiotic resistance. There are an estimated 106 million cases per year worldwide, there is no vaccine available to prevent infection, and N. gonorrhoeae strains that are resistant to all antibiotics routinely used to treat the infection have emerged.

Altered Spatial and Temporal Gait Parameters in Mice Infected with Ross River Virus.

Infection with mosquito-borne arthritogenic alphaviruses, such as Ross River virus (RRV) and Barmah Forest virus (BFV), can lead to long-lasting rheumatic disease. Existing mouse models that recapitulate the disease signs and immunopathogenesis of acute RRV and BFV infection have consistently shown relevance to human disease. However, these mouse models, which chiefly model hindlimb dysfunction, may be prone to subjective interpretation when scoring disease.

The Novel bis-1,2,4-Triazine MIPS-0004373 Demonstrates Rapid and Potent Activity against All Blood Stages of the Malaria Parasite.

Novel bis-1,2,4-triazine compounds with potent activity against Plasmodium falciparum parasites were recently identified. The bis-1,2,4-triazines represent a unique antimalarial pharmacophore and are proposed to act by a novel but as-yet-unknown mechanism of action. This study investigated the activity of the bis-1,2,4-triazine MIPS-0004373 across the mammalian life cycle stages of the parasite and profiled the kinetics of activity against blood and transmission stage parasites and .

The dCache Chemoreceptor TlpA of Helicobacter pylori Binds Multiple Attractant and Antagonistic Ligands via Distinct Sites.

The Helicobacter pylori chemoreceptor TlpA plays a role in dampening host inflammation during chronic stomach colonization. TlpA has a periplasmic dCache_1 domain, a structure that is capable of sensing many ligands; however, the only characterized TlpA signals are arginine, bicarbonate, and acid. To increase our understanding of TlpA's sensing profile, we screened for diverse TlpA ligands using ligand binding arrays.

Copper Intoxication in Group B Streptococcus Triggers Transcriptional Activation of the Operon That Contributes to Enhanced Virulence during Acute Infection.

Bacteria can utilize copper (Cu) as a trace element to support cellular processes; however, excess Cu can intoxicate bacteria. Here, we characterize the operon in group B streptococcus (GBS) and establish its role in evasion of Cu intoxication and the response to Cu stress on virulence. Growth of a GBS mutant deficient in the Cu exporter was severely compromised under Cu stress conditions.