Intra-serotype variation of capsule and its quantification.

Unlabelled: () is a leading respiratory pathogen that depends on a thick layer of capsular polysaccharide (CPS) to evade immune clearance. Disease prevention by CPS-based vaccines is limited because of the species' high genome plasticity and ability to express over 100 different capsule types (serotypes). Generally, intra-serotype variations in capsulation are overlooked, despite the genetic variability of the bacterium.

Health Care Facility Characteristics Associated With Providing Telehealth HIV Care Services During the COVID-19 Pandemic.

To describe provision of HIV telehealth services during the COVID-19 pandemic using data from the Centers for Disease Control and Prevention (CDC) Medical Monitoring Project Facility Survey for the Ending the HIV Epidemic in the United States initiative, which aims to achieve an at least 90% reduction in new HIV infections by 2030 and highlights telehealth as an important strategy. During 2021, we surveyed 1023 facilities providing HIV care to a nationally representative sample of US adults with diagnosed HIV, of which 45% responded. We calculated weighted percentages with 95% confidence intervals comparing the characteristics of facilities providing telehealth services.

Neuraminidase-mediated enhancement of colonization is associated with altered mucus characteristics and distribution.

Unlabelled: Upon entry into the upper respiratory tract (URT), (Spn) upregulates neuraminidases (NA) that cleave sialic acid (SA) from host glycans. Because sialylation is thought to contribute to the physical properties that determine mucus function, we posited that Spn directly alters host mucus through NA activity. By directly imaging the colonized URT, we demonstrated NA-mediated alterations to the characteristics and distribution of mucus along the respiratory epithelium, where colonizing bacteria are found.

Pneumococcal pneumonia is driven by increased bacterial turnover due to bacteriocin-mediated intra-strain competition.

Using chromosomal barcoding, we observed that >97% of the Streptococcus pneumoniae (Spn) population turns over in the lung within 2 days post-inoculation in a murine model. This marked collapse of diversity and bacterial turnover was associated with acute inflammation (severe pneumococcal pneumonia), high bacterial numbers in the lungs, bacteremia, and mortality. Intra-strain competition mediated by the blp locus, which expresses bacteriocins in a quorum-sensing-dependent manner, was required for each of these effects.

RSV and rhinovirus increase pneumococcal carriage acquisition and density, whereas nasal inflammation is associated with bacterial shedding.

Epidemiological studies report the impact of co-infection with pneumococcus and respiratory viruses upon disease rates and outcomes, but their effect on pneumococcal carriage acquisition and bacterial load is scarcely described. Here, we assess this by combining natural viral infection with controlled human pneumococcal infection in 581 healthy adults screened for upper respiratory tract viral infection before intranasal pneumococcal challenge. Across all adults, respiratory syncytial virus (RSV) and rhinovirus asymptomatic infection confer a substantial increase in secondary infection with pneumococcus.

Unmet Needs for Ancillary Services by Provider Type Among People With Diagnosed Human Immunodeficiency Virus.

Background: Unmet needs for ancillary services are substantial among people with human immunodeficiency virus (PWH), and provider type could influence the prevalence of unmet needs for these services.

Methods: Data from a national probability sample of PWH were analyzed from the Centers for Disease Control and Prevention's Medical Monitoring Project. We analyzed 2019 data on people who had ≥1 encounter with a human immunodeficiency virus (HIV) care provider (N = 3413) and their care facilities.

Impaired upper respiratory tract barrier function during postnatal development predisposes to invasive pneumococcal disease.

Infants are highly susceptible to invasive respiratory and gastrointestinal infections. To elucidate the age-dependent mechanism(s) that drive bacterial spread from the mucosa, we developed an infant mouse model using the prevalent pediatric respiratory pathogen, Streptococcus pneumoniae (Spn). Despite similar upper respiratory tract (URT) colonization levels, the survival rate of Spn-infected infant mice was significantly decreased compared to adults and corresponded with Spn dissemination to the bloodstream.

Pathway-based, reaction-specific annotation of disease variants for elucidation of molecular phenotypes.

Germline and somatic mutations can give rise to proteins with altered activity, including both gain and loss-of-function. The effects of these variants can be captured in disease-specific reactions and pathways that highlight the resulting changes to normal biology. A disease reaction is defined as an aberrant reaction in which a variant protein participates.

Quorum-sensing system of primes gene expression for protection from lethal oxidative stress.

The quorum-sensing system links metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of HO, a crucial host defense against . We now report that protection by surprisingly extends beyond post-exponential growth to the exit from stationary phase when the system is no longer turned on. Thus, can be considered a constitutive protective factor.

Prevalence of Diagnosed and Undiagnosed Depression Among US Adults with Human Immunodeficiency Virus: Data from the Medical Monitoring Project.

People with human immunodeficiency virus (PWH) are disproportionately affected by depression, but the recent national estimates for US PWH encompassing both current symptoms and clinical diagnoses to assess missed diagnoses and lack of symptom remission are lacking. We used data from CDC's Medical Monitoring Project (MMP) to report nationally representative estimates of diagnosed and undiagnosed depression among US adult PWH. During June 2021 to May 2022, MMP collected interview data on symptoms consistent with major or other depression and depression diagnoses from medical records of 3928 PWH.

Individual Atg8 paralogs and a bacterial metabolite sequentially promote hierarchical CASM-xenophagy induction and transition.

Atg8 paralogs, consisting of LC3A/B/C and GBRP/GBRPL1/GATE16, function in canonical autophagy; however, their function is controversial because of functional redundancy. In innate immunity, xenophagy and non-canonical single membranous autophagy called "conjugation of Atg8s to single membranes" (CASM) eliminate bacteria in various cells. Previously, we reported that intracellular Streptococcus pneumoniae can induce unique hierarchical autophagy comprised of CASM induction, shedding, and subsequent xenophagy.

Do HIV Care Outcomes Differ by Provider Type?

Background: We compared HIV care outcomes by HIV provider type to inform efforts to strengthen the HIV provider workforce.

Setting: United States.

Methods: We analyzed data from Center for Disease Control and Prevention's Medical Monitoring Project collected during June, 2019-May, 2021 from 6323 adults receiving HIV medical care.

Inhibiting influenza virus transmission using a broadly acting neuraminidase that targets host sialic acids in the upper respiratory tract.

The ongoing transmission of influenza A viruses (IAV) for the past century continues to be a burden to humans. IAV binds terminal sialic acids (SA) of sugar molecules present within the upper respiratory tract (URT) in order to successfully infect hosts. The two most common SA structures that are important for IAV infection are those with α2,3- and α2,6-linkages.

Synthetic genetic oscillators demonstrate the functional importance of phenotypic variation in pneumococcal-host interactions.

Phenotypic variation is the phenomenon in which clonal cells display different traits even under identical environmental conditions. This plasticity is thought to be important for processes including bacterial virulence, but direct evidence for its relevance is often lacking. For instance, variation in capsule production in the human pathogen Streptococcus pneumoniae has been linked to different clinical outcomes, but the exact relationship between variation and pathogenesis is not well understood due to complex natural regulation.

The Reactome Pathway Knowledgebase 2024.

The Reactome Knowledgebase (https://reactome.org), an Elixir and GCBR core biological data resource, provides manually curated molecular details of a broad range of normal and disease-related biological processes. Processes are annotated as an ordered network of molecular transformations in a single consistent data model.

Pathway-based, reaction-specific annotation of disease variants for elucidation of molecular phenotypes.

Disease variant annotation in the context of biological reactions and pathways can provide a standardized overview of molecular phenotypes of pathogenic mutations that is amenable to computational mining and mathematical modeling. Reactome, an open source, manually curated, peer-reviewed database of human biological pathways, provides annotations for over 4000 disease variants of close to 400 genes in the context of ∼800 disease reactions constituting ∼400 disease pathways. Functional annotation of disease variants proceeds from normal gene functions, through disease variants whose divergence from normal molecular behaviors has been experimentally verified, to extrapolation from molecular phenotypes of characterized variants to variants of unknown significance using criteria of the American College of Medical Genetics and Genomics (ACMG).

Effects of Capsular Polysaccharide amount on Pneumococcal-Host interactions.

Among the many oral streptococci, Streptococcus pneumoniae (Spn) stands out for the capacity of encapsulated strains to cause invasive infection. Spread beyond upper airways, however, is a biological dead end for the organism, raising the question of the benefits of expending energy to coat its surface in a thick layer of capsular polysaccharide (CPS). In this study, we compare mutants of two serotypes expressing different amounts of CPS and test these in murine models of colonization, invasion infection and transmission.

Impact and cost-effectiveness of short-course tuberculosis preventive treatment for household contacts and people with HIV in 29 high-incidence countries: a modelling analysis.

Background: Guidelines and implementation of tuberculosis preventive treatment (TPT) vary by age and HIV status. Specifically, TPT is strongly recommended for people living with HIV/AIDS (PLWHA) and household contacts younger than 5 years but only conditionally recommended for older contacts. Cost remains a major barrier to implementation.

Targeting host sialic acids in the upper respiratory tract with a broadly-acting neuraminidase to inhibit influenza virus transmission.

The ongoing transmission of influenza A viruses (IAV) for the past century continues to be a burden to humans. IAV binds terminal sialic acids (SA) of sugar molecules present within the upper respiratory tract (URT) in order to successfully infect hosts. The two most common SA structures that are important for IAV infection are those with α2,3- and α2,6-linkages.

Rewiring capsule production by CRISPRi-based genetic oscillators demonstrates a functional role of phenotypic variation in pneumococcal-host interactions.

Phenotypic variation is the phenomenon in which clonal cells display different traits even under identical environmental conditions. This plasticity is thought to be important for processes including bacterial virulence, but direct evidence for its relevance is often lacking. For instance, variation in capsule production in the human pathogen has been linked to different clinical outcomes, but the exact relationship between variation and pathogenesis is not well understood due to complex natural regulation.