SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins.

As of 2024, SARS-CoV-2 continues to propagate and drift as an endemic virus, impacting healthcare for years. The largest sequencing initiative for any species was initiated to combat the virus, tracking changes over time at a full virus base-pair resolution. The SARS-CoV-2 sequencing represents a unique opportunity to understand selective pressures and viral evolution but requires cross-disciplinary approaches from epidemiology to functional protein biology.

Evaluation of 4 molecular assays as part of a 2-step algorithm for the detection of Clostridium difficile in stool specimens.

Detection of Clostridium difficile infection is important for clinical laboratories, owing to debilitating disease, severe outcomes, patient awareness, and public reporting of hospital data. This study evaluated the performance of 4 nucleic acid amplification test (NAAT) assays as part of a 2-step algorithm that involves reflexive NAAT following enzyme immunoassay (EIA) testing that is indeterminate for glutamate dehydrogenase (GDH) antigen and toxin A/B (GDH/toxin or GDH/toxin). A total of 500 stool specimens from consecutive patients were tested by each of the 5 methods and also evaluated as part of a 2-step algorithm.

Diagnosis of active tuberculosis disease: From microscopy to molecular techniques.

Methods used for the laboratory diagnosis of tuberculosis are continually evolving in order to achieve more rapid, less expensive, and accurate results. Acid-fast staining and culture for mycobacteria remain at the core of any diagnostic algorithm. Following growth in culture, molecular technologies such as nucleic acid hybridization probes, MALDI-TOF MS, and DNA sequencing may be used for definitive species identification.

Lyme Disease Coinfections in the United States.

Lyme disease in North America is caused by infection with the spirochetal bacterium Borrelia burgdorferi and transmitted by Ixodes scapularis and Ixodes pacificus ticks. These ticks also have the potential to transmit a rapidly expanding list of other pathogenic bacteria, viruses, and parasites, including Anaplasma phagocytophilum, Babesia microti, deer tick (Powassan) virus, Borrelia miyamotoi, and the Ehrlichia muris-like organism. Coinfections with B burgdorferi and these other agents are often difficult to diagnose and may go untreated, and thus contribute significantly to patient morbidity and mortality from tick-borne infections.

Production of outer membrane vesicles by the plague pathogen Yersinia pestis.

Many Gram-negative bacteria produce outer membrane vesicles (OMVs) during cell growth and division, and some bacterial pathogens deliver virulence factors to the host via the release of OMVs during infection. Here we show that Yersinia pestis, the causative agent of the disease plague, produces and releases native OMVs under physiological conditions. These OMVs, approximately 100 nm in diameter, contain multiple virulence-associated outer membrane proteins including the adhesin Ail, the F1 outer fimbrial antigen, and the protease Pla.

The Pla protease of Yersinia pestis degrades fas ligand to manipulate host cell death and inflammation.

Pneumonic plague is a deadly respiratory disease caused by Yersinia pestis. The bacterial protease Pla contributes to disease progression and manipulation of host immunity, but the mechanisms by which this occurs are largely unknown. Here we show that Pla degrades the apoptotic signaling molecule Fas ligand (FasL) to prevent host cell apoptosis and inflammation.

Genome-wide analysis of small RNAs expressed by Yersinia pestis identifies a regulator of the Yop-Ysc type III secretion system.

Small noncoding RNA (sRNA) molecules are integral components of the regulatory machinery for many bacterial species and are known to posttranscriptionally regulate metabolic and stress-response pathways, quorum sensing, virulence factors, and more. The Yop-Ysc type III secretion system (T3SS) is a critical virulence component for the pathogenic Yersinia species, and the regulation of this system is tightly controlled at each step from transcription to translocation of effectors into host cells. The contribution of sRNAs to the regulation of the T3SS in Yersinia has been largely unstudied, however.

Posttranscriptional regulation of the Yersinia pestis cyclic AMP receptor protein Crp and impact on virulence.

Unlabelled: The cyclic AMP receptor protein (Crp) is a transcriptional regulator that controls the expression of numerous bacterial genes, usually in response to environmental conditions and particularly by sensing the availability of carbon. In the plague pathogen Yersinia pestis, Crp regulates the expression of multiple virulence factors, including components of the type III secretion system and the plasminogen activator protease Pla. The regulation of Crp itself, however, is distinctly different from that found in the well-studied Escherichia coli system.

RfaL is required for Yersinia pestis type III secretion and virulence.

Yersinia pestis, the causative agent of plague, uses a type III secretion system (T3SS) to inject cytotoxic Yop proteins directly into the cytosol of mammalian host cells. The T3SS can also be activated in vitro at 37°C in the absence of calcium. The chromosomal gene rfaL (waaL) was recently identified as a virulence factor required for proper function of the T3SS.