New York State Department of Health

Glyphosate, the active ingredient in herbicide Roundup, is the most widely used environmental contaminant that has been extensively studied for its potential carcinogenic effects. In the US alone, a staggering 81% of the US population ≥6 years of age is exposed to glyphosate. Notably, this coincides with the alarming rise in the incidence of hypertension, the single largest risk factor for global mortality through cardiovascular diseases. Here we asked if there is a link between glyphosate exposure and hypertension, the premise being that glyphosate targets the shikimate pathway present in gut microbiota coupled with more recent knowledge that gut microbiota causally regulate blood pressure. We hypothesized that glyphosate elevates hypertension through microbiota-mediated mechanisms and document a highly concerning detrimental effect of glyphosate by demonstrating a causal link between oral glyphosate exposure and significant elevation in blood pressure. Gut microbiota was identified as the central mediator of this effect. Mechanistically, glyphosate-mediated elevation in blood pressure was through disruption of both gut-liver and gut-vascular homeostasis via FXR-signaling and accumulation of the microbial metabolite shikimic acid, respectively. Together, these findings underscore the need to reconsider the unabated use of this herbicide, which adversely affects a cardinal sign of health.

Lyme carditis is a rare, potentially fatal manifestation of Lyme disease. Although Lyme disease is nationally notifiable, data on clinical manifestations are not collected systematically in the United States. We developed a syndromic surveillance definition to identify patients with Lyme carditis in New York State during 2017-2021. We developed a definition of Lyme carditis by using diagnostic codes and keywords to identify emergency department visits related to Lyme carditis through the National Syndromic Surveillance Program's BioSense Platform. We systematically abstracted information for each identified patient by reviewing medical records in New York State's regional health information exchange system. Physician reviewers independently assigned a clinical case status to each record. We mapped cases of Lyme carditis by county and described their characteristics. We identified records for 173 individuals; 32% (n = 55) were classified as confirmed, 16% (n = 27) as probable, and 53% (n = 91) as not a case of Lyme carditis. In total, we identified 82 cases of confirmed or probable Lyme carditis; the positive predictive value of the definition was 47%. Cases occurred in 49% of New York State counties and peaked annually in July and August. Among patients with confirmed and probable Lyme carditis, age distribution was bimodal, with incidence peaking at about ages 32 and 70 years; 71% were male. Eighty-four percent had positive 2-tiered serologic test results for Lyme disease, and second- or third-degree atrioventricular block was present in two-thirds of patients (67%). This definition may be a useful tool to detect changing patterns of Lyme carditis in areas with a high incidence of Lyme disease.

BackgroundGroup A Streptococcus (GAS) is highly contagious and can cause invasive infections including bacteremia, sepsis, and necrotizing fasciitis. Thus, it is important to limit transmission and treat infections promptly and appropriately. In 2019, the Centers for Disease Control and Prevention (CDC) listed resistant GAS as a concerning threat due to increasing rates of clindamycin (CLI) and erythromycin (ERY) resistance. The Wadsworth Center (WC) is one of 10 laboratories in the country funded to perform GAS surveillance through the Emerging Infections Program (EIP) and receives isolates of GAS from hospitals, laboratories, and local health departments. WC also receives isolates from healthcare-associated investigations. In the past 6 years, over 2,200 GAS isolates have been received, including isolates from over 100 outbreaks.MethodsThese isolates are analyzed using multiple methods for identification and characterization, including antimicrobial resistance (AR) and whole genome sequencing (WGS). Antimicrobial susceptibility testing (AST) is performed using the bioMérieux E-test gradient strip to assess increased resistance to CLI and ERY.ResultsTo date, WC has tested over 1,400 GAS isolates and identified CLI resistance in 130 isolates and ERY resistance in 230 isolates. Inducible clindamycin resistance (ICR) in GAS can develop when the pathogen is exposed to other antibiotics, such as ERY, and can result in treatment failure. To address this concern, the ICR test is currently under validation and will be used alongside the E-test when applicable. In addition to culture AST, isolates are sent for WGS and analyzed using an AR bioinformatic gene detection pipeline to screen for genes potentially leading to AR in strains circulating in New York State (NYS). To date, this method has identified over 400 samples containing one or more AR genes. Data analysis is underway to assess the relationship between the presence of AR genes and the correlation with phenotypic AST results.ConclusionThe surveillance testing performed at WC represents an extensive testing algorithm that can be used for the identification of trends in antimicrobial resistance in GAS. Data analysis may lead to the development of new assays to improve testing algorithms at WC and other public health laboratories.DisclosuresAll Authors: No reported disclosures

CRISPR-Cas systems are prokaryotic adaptive immune systems that use RNA-guided protein complexes to target invading nucleic acid. A surveillance complex consisting of protein and a CRISPR-RNA (crRNA) binds target nucleic acid via base-pairing interactions, typically leading to processing of the target nucleic acid by a nuclease. CRISPR-Cas systems are classified based on their mechanism of action, with type I systems being the most prevalent in nature. Type I CRISPR-Cas systems target DNA, and require extensive complementarity between the crRNA and the target DNA. Moreover, type I systems require the presence of a “Protospacer Adjacent Motif” (PAM) sequence in the target DNA immediately adjacent to the expected region of base-pairing with the crRNA. Classical biotypes of the bacterial pathogen Vibrio cholerae have active type I-E CRISPR-Cas systems. While the optimal PAM sequence for this CRISPR-Cas system is known to be AAY, the activity of other sequences as possible PAMs has not been determined. Here, we quantify the effectiveness of all possible trinucleotide sequences in the PAM position for the V. cholerae type I-E CRISPR-Cas system. Our data indicate a hierarchy of PAM efficacy, with 15 of the 64 trinucleotide sequences functioning as a PAM.

Ribosomes translate the genetic code in mRNA to synthesize proteins in all living organisms. Decoding of mRNA occurs in the small subunit of the ribosome and is mediated by tRNA anticodons. Regions near the decoding center are a target for antibiotics, such as aminoglycosides and tetracyclines, where their presence results in errors in protein synthesis. More than two decades of high-resolution structural studies have shown how such medically important antimicrobials (MIAs) bind to the small subunit of the bacterial ribosome. Here, we comprehensively analyze these previously reported structures to help understand the variability with which MIAs bind to small subunits of bacterial ribosomes. We previously solved the hibernating 70S ribosome structure of the bacterial pathogen Borrelia burgdorferi (Bbu), the causative agent of Lyme disease, but there is no structure of any MIA bound to this ribosome reported. Our structural analysis makes it possible to use inexpensive computational methods to predict binding of these MIAs to the Bbu ribosomal 30S small subunit. For this, we used structural analogy, restrained energy minimization, and single-point binding free energy computations. We find the single-point binding free energy of the MIAs to be very sensitive to small conformational changes in the MIA and its environment. Incorporating this knowledge in structure-guided design could aid in development of narrow-spectrum MIAs targeting specific bacterial pathogens.

In the neonatal intensive care unit (NICU), outbreaks caused by methicillin-susceptible Staphylococcus aureus (MSSA) are less commonly described than outbreaks caused by methicillin-resistant Staphylococcus aureus (MRSA) despite the increased burden of MSSA infections. To investigate a NICU MSSA outbreak utilizing whole-genome sequencing (WGS) and multi-locus sequencing typing (MLST) to identify transmission events. An investigation was initiated in a level IV NICU after four patients developed MSSA skin and soft tissue infections (SSTI) within threeweeks. MLST and WGS were performed on MSSA isolates obtained from clinical and surveillance specimens. During the outbreak, 16 infants developed MSSA infections including SSTIs (n = 15) and bacteremia (n = 1). Thirteen SSTIs presented on neonates' faces, all of whom were on non-invasive respiratory support. During 7 rounds of surveillance, an additional 31 patients were found to be colonized with MSSA. MLST identified a predominant cluster (ST-121). WGS found that all ST-121 isolates were closely related (≤10 genetic variants between isolates) suggesting likely transmission events, harbored the mupA gene, exhibited mupirocin MIC values ≥1,024 µg/mL, and were associated with infection. Multiple infection control measures were implemented including the "bare below the elbows" practice. No further mupirocin-resistant isolates were recovered or ST-121 SSTIs identified after Week 26. WGS analysis furthered the MLST analysis and identified a single MLST as the outbreak-related strain. Successful control of this outbreak was achieved with a multitude of infection prevention and control methods.

The prevalence of cardiovascular disease differs substantially across neighborhoods. However, few studies have examined the contribution of neighborhood-level structural racism to inequities in cardiovascular health. To investigate the association between neighborhood-level manifestations of structural racism and the prevalence of cardiovascular clinical and behavioral risk factors and cardiovascular diseases. This cross-sectional study consisted of 71 915 US census tracts. The Structural Racism Effect Index (SREI) was appended to the 2020 Centers for Disease Control and Prevention's PLACES dataset. Race and ethnicity were self-reported and obtained from the 2019 American Community Survey 5-year estimates. Data analysis was conducted from June 2024 to October 2024. The SREI is a composite score of census tract measures within 9 domains affected by structural racism (built environment, criminal justice, education, employment, housing, income and poverty, social cohesion, transportation, and wealth). The SREI scores were categorized into distribution-based quintiles, where higher quintiles represented greater neighborhood structural racism. Neighborhood-level prevalence of cardiovascular clinical (high blood pressure, high cholesterol, obesity, and diabetes) and behavioral (current cigarette smoking and no leisure-time physical activity) risk factors and cardiovascular disease (coronary heart disease and stroke). Multilevel-linear mixed models, adjusting for confounders, were used to estimate adjusted prevalence rate ratios (aPRR). Among 71 915 census tracts, neighborhoods in the highest quintiles of structural racism were more likely than neighborhoods in the lowest quintile to be in the southern region (quintile 1, 19.9% vs quintile 5, 56.8%). The proportion of the population that was Black was largest in neighborhoods in the highest quintile of structural racism (quintile 1, 2.2% vs quintile 5, 23.0%). After adjustment, compared with the lowest quintile of structural racism, the highest quintile had significantly higher prevalence rates of cardiovascular clinical risk factors, including high blood pressure (aPRR, 1.37; 95% CI, 1.37-1.38), obesity (aPRR, 1.40; 95% CI, 1.39-1.40), and diabetes (aPRR, 1.80; 95% CI, 1.79-1.81). Similarly, for cardiovascular behavioral risk factors, the highest quintile of structural racism had significantly higher prevalence rates of current cigarette smoking (aPRR, 1.84; 95% CI, 1.83-1.85) and no leisure-time physical activity (aPRR, 1.88; 95% CI, 1.87-1.89). Additionally, for cardiovascular diseases, the highest quintile of structural racism had higher prevalence rates of coronary heart disease (aPRR, 1.80; 95% CI, 1.79-1.82) and stroke (aPRR, 1.99; 95% CI, 1.98-2.00). In this cross-sectional study, structural racism was associated with inequities in neighborhood cardiovascular health, highlighting opportunities for place-based prevention efforts.