Epidemiological, Phylogenetic, and Resistance Heterogeneity Among in a Large U.S. Deep South Healthcare system.

Background: () disease in the United States is commonly attributed to outbreaks of 1 or 2 monophyletic carbapenem resistance (CR) lineages that vary by region. However, there is limited knowledge regarding CR epidemiology and population structures in the U.S.

Genome sequences of 36 strains optimized for the multiplexed opsonophagocytosis killing assay.

A multiplexed opsonophagocytosis assay (MOPA) was developed as a cost-effective, high-throughput biological assay to evaluate the efficacy of pneumococcal vaccines by measurement of opsonophagocytic activity of anti-capsular antibodies. Here, we report draft genomes of the 36 strains of developed for use in the reference pneumococcal MOPA.

Novel pneumococcal capsule type 33E results from the inactivation of glycosyltransferase WciE in vaccine type 33F.

The polysaccharide (PS) capsule is essential for immune evasion and virulence of Streptococcus pneumoniae. Existing pneumococcal vaccines are designed to elicit anticapsule antibodies; however, the effectiveness of these vaccines is being challenged by the emergence of new capsule types or variants. Herein, we characterize a newly discovered capsule type, 33E, that appears to have repeatedly emerged from vaccine type 33F via an inactivation mutation in the capsule glycosyltransferase gene, wciE.

Effect of withdrawing an immunomodulatory feed additive from lactating cow diets on peripheral blood mononuclear cell proliferation.

Supplementation of immunomodulatory feed additives, such as OmniGen AF (OG), helps to maintain immune competency; however, it is unknown if immune benefits persist in lactating cows after OG is removed from the diet. The aim of this trial was to evaluate the effect of withdrawing OG from the diet on peripheral blood mononuclear cells (PBMC) proliferation of midlactation dairy cows. Multiparous Holstein cows (N = 32), blocked by parity (2.

Hormonal and immunological responses of Holstein dairy cows from late lactation to the dry period and from the dry period to early lactation.

Parturition and dry-off are challenging events for dairy cows partially due to changes in endocrine responses. The aim of this experiment was to evaluate blood concentrations of cortisol and prolactin and their effects on proliferation of peripheral blood mononuclear cells (PBMC) with or without stimulation by common immune cell mitogens (lipopolysaccharide [LPS], and concanavalin A [ConA]) of multiparous dairy cows from late lactation to the dry period and from the dry period to early lactation. Two groups of cows were enrolled: cows from late lactation to the dry period enrolled at 8 d before dry-off (LTD, n = 6, days in milk at dry-off = 332 ± 41 d) and cows from the dry period to early lactation enrolled at 7 d before expected calving date (DTL, n = 7).

Discovery and Characterization of Pneumococcal Serogroup 36 Capsule Subtypes, Serotypes 36A and 36B.

Streptococcus pneumoniae can produce a wide breadth of antigenically diverse capsule types, a fact that poses a looming threat to the success of vaccines that target pneumococcal polysaccharide (PS) capsule. Yet, many pneumococcal capsule types remain undiscovered and/or uncharacterized. Prior sequence analysis of pneumococcal capsule synthesis () loci suggested the existence of capsule subtypes among isolates identified as "serotype 36" according to conventional capsule typing methods.

Outpatient Clonal Propagation and Rapid Regional Establishment of an Emergent Carbapenem-Resistant Acinetobacter baumannnii Lineage Sequence Type 499Pas.

Eliminating carbapenem-resistant Acinetobacter baumannii (CRAb) disease requires comprehensive knowledge of how this noncommensal organism propagates among at-risk hosts. We molecularly characterized an ongoing surge of CRAb cases among patients in a Midwest US healthcare system, which coincided with sustained reductions in hospital-acquired CRAb infections and falloffs of cases associated with distinctly more resistant antibiotypes. Genome sequencing revealed surge isolates belonged to an emergent Pasteur scheme sequence type 499 and comprised multiple contemporaneous clonal clusters.

injection drug use-associated bloodstream infections are propagated by community outbreaks of diverse lineages.

Background: The ongoing injection drug use (IDU) crisis in the United States has been complicated by an emerging epidemic of IDU-associated bloodstream infections (IDU-BSI).

Methods: We performed a case-control study comparing IDU-BSI and non-IDU BSI cases identified in a large US Midwestern academic medical center between Jan 1, 2016 and Dec 21, 2019. We obtained the whole-genome sequences of 154  IDU-BSI and 91  non-IDU BSI cases, which were matched with clinical data.

Ficolin-2 Lectin Complement Pathway Mediates Capsule-Specific Innate Immunity Against Invasive Pneumococcal Disease.

Reports conflict regarding which lectin-microbial ligand interactions elicit a protective response from the lectin pathway (LP) of complement. Using fluorescent microscopy, we demonstrate the human lectin ficolin-2 binds to serotype 11A capsule polysaccharide dependent on the O-acetyltransferase gene . This triggers complement deposition and promotes opsonophagocytosis of encapsulated pneumococci.

Comparison of the Clinical Characteristics of Hospital-Acquired and Non-Hospital-Acquired Complex in a Large Midwest US Health Care System.

We retrospectively compared the clinical characteristics of hospital-acquired (HA) vs non-hospital-acquired (nHA) complex isolates in a large health care system in St. Louis, Missouri, from 2007 to 2017. More than 60% of the total isolates were nHA; they were predominantly from nonrespiratory sources and exhibited ~40% carbapenem resistance rates and stably persisted, though HA occurrence waned.

Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes.

Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and bloodstream infections, even though one in five A. baumannii strains are isolated from urinary sites.

Seasonal Changes in the Prevalence of Antibiotic-Susceptible Complex Isolates Result in Increased Multidrug Resistance Rates During Winter Months.

Temporal analysis of complex isolates in a large, US healthcare system demonstrated decreased occurrence of antibiotic-susceptible isolates between November and May, while resistant isolate occurrence was temporally stable. This resulted in 50%-100% seasonal increases of resistance rates. This work offers insight into the phenomenon of Gram-negative pathogen seasonality.

Low invasiveness of pneumococcal serotype 11A is linked to ficolin-2 recognition of O-acetylated capsule epitopes and lectin complement pathway activation.

Background: The divergent epidemiological behavior of Streptococcus pneumoniae serotypes suggests that serotype-specific features such as capsule O-acetylation influence the propensity of a strain to cause invasive pneumococcal disease (IPD). We hypothesize that innate host factors mediate the observed negative association between IPD and the serotype 11A (ST11A) capsule O-acetyltransferase gene, wcjE.

Methods: We evaluated the ability of ficolin-2, an initiator of the lectin complement pathway that was previously shown to bind ST11A pneumococci, to recognize and mediate complement-dependent opsonophagocytosis of different pneumococcal serotypes.

Spectrum of pneumococcal serotype 11A variants results from incomplete loss of capsule O-acetylation.

Streptococcus pneumoniae is a significant bacterial pathogen that expresses >90 capsule serotypes. Conventional serotyping methods assume that each serotype is a genetically and antigenically distinct entity; however, recent investigations have revealed pneumococcal isolates that cannot be unambiguously serotyped because they share the properties of more than one serotype. Here, we employed a novel serotyping method and NMR spectroscopy to examine clinical isolates sharing properties of serotypes 11A and 11E.

Streptococcus pneumoniae serotype 11D has a bispecific glycosyltransferase and expresses two different capsular polysaccharide repeating units.

Streptococcus pneumoniae (pneumococcus) expresses a capsular polysaccharide (CPS) that protects against host immunity and is synthesized by enzymes in the capsular polysaccharide synthesis (cps) locus. Serogroup 11 has six members (11A to -E) and the CPS structure of all members has been solved, except for serotype 11D. The cps loci of 11A and 11D differ by one codon (N112S) in wcrL, which putatively encodes a glycosyltransferase that adds the fourth sugar of the CPS repeating unit (RU).

Biochemical, genetic, and serological characterization of two capsule subtypes among Streptococcus pneumoniae Serotype 20 strains: discovery of a new pneumococcal serotype.

The bacterial pathogen Streptococcus pneumoniae expresses one of over 90 structurally distinct polysaccharide (PS) capsule serotypes. Prior PS structural analyses of the vaccine-associated serotype 20 do not agree with reports describing the genes that mediate capsule synthesis. Furthermore, using immunized human sera-based assays, serological differences were recently noted among strains typed as serotype 20.

Structural characterization of Streptococcus pneumoniae serotype 9A capsule polysaccharide reveals role of glycosyl 6-O-acetyltransferase wcjE in serotype 9V capsule biosynthesis and immunogenicity.

The putative capsule O-acetyltransferase gene wcjE is highly conserved across various Streptococcus pneumoniae serotypes, but the role of the gene in capsule biosynthesis and bacterial fitness remains largely unclear. Isolates expressing pneumococcal serotype 9A arise from precursors expressing wcjE-associated serotype 9V through loss-of-function mutation to wcjE. To define the biosynthetic role of 9V wcjE, we characterized the structure and serological properties of serotype 9V and 9A capsule polysaccharide (PS).

Differential occurrence of Streptococcus pneumoniae serotype 11E between asymptomatic carriage and invasive pneumococcal disease isolates reflects a unique model of pathogen microevolution.

Background: Streptococcus pneumoniae is a commensal colonizer of the human nasopharynx (NP) that causes disease after evasion of host defenses and dissemination. Pneumococcal strains expressing the newly identified serotype 11E arise from antigenically similar 11A progenitors by genetic inactivation of the O-acetyltransferase gene wcjE. Each 11E strain contains a distinct mutation to wcjE, suggesting that 11E strains are not transmitted among hosts despite their recovery from multiple patients with pneumococcal disease.

Streptococcus pneumoniae serotype 9A isolates contain diverse mutations to wcjE that result in variable expression of serotype 9V-specific epitope.

Background: Streptococcus pneumoniae is a significant pathogen capable of expressing protective and antigenically diverse capsules. To better understand the molecular basis of capsular antigenic diversity, we investigated the hypothetical serological role of wcjE, which encodes a capsule O-acetyltransferase, in the vaccine-targeted serotype 9V and related serotype 9A.

Methods: We inactivated wcjE by recombination in a serotype 9V strain and determined wcjE sequences of 11 serotype 9A clinical isolates.

Elucidation of structural and antigenic properties of pneumococcal serotype 11A, 11B, 11C, and 11F polysaccharide capsules.

Despite the emerging impact of serogroup 11 serotypes in Streptococcus pneumoniae epidemiology, the structures of serogroup 11 capsule types have not been fully elucidated, particularly the locations of O-acetyl substitutions. Here, we report the complete structures of the serotype 11B, 11C, and 11F polysaccharides and a revision to the serotype 11A capsular polysaccharide using nuclear magnetic resonance (NMR). All structures shared a linear, tetrasaccharide backbone with a pendant phosphopolyalcohol.

Contraceptive discontinuation among Honduran women who use reversible methods.

A panel study examining the effects of women's individual characteristics, side effects experienced, and service quality on their contraceptive discontinuation was undertaken in four urban areas of Honduras. Data were collected from October 2006 to December 2007. The baseline sample consisted of 800 women aged 15-44 who were new or continuing users of an injectable contraceptive, the IUD, or an oral contraceptive.

A new pneumococcal serotype, 11E, has a variably inactivated wcjE gene.

Recently, 2 serologically and biochemically distinct subtypes-11Aalpha and 11Abeta-were discovered among serotype 11A isolates of Streptococcus pneumoniae. Sequence comparison of the capsular polysaccharide synthesis (cps) loci of the 2 subtypes identified disruption of the wcjE gene, a putative O-acetyltransferase, as the genetic hallmark of the 11Abeta phenotype. Directed disruption of wcjE in vitro in an 11Aalpha strain switched the strain to the 11Abeta phenotype, confirming the role played by the gene in the divergence between the subtypes.

Survey of nonsusceptible nasopharyngeal Streptococcus pneumoniae isolates in children attending day-care centers in Brazil.

A survey of nasopharyngeal carriage of penicillin nonsusceptible pneumococcal (PNSp) isolates was conducted among 1192 children attending 62 day care centers in Brazil, where pneumococcal vaccination has not been routinely introduced. Nasopharyngeal pneumococcal carriage was detected in 686 (57.6%) infants, and 178 (25.