Genes Differentially Expressed Across Major Arteries Are Enriched in Endothelial Dysfunction-Related Gene Sets: Implications for Relative Inter-artery Atherosclerosis Risk.

Atherosclerosis differs across major arteries. Although the biological basis is not fully understood, limited evidence of genetic differences has been documented. This study, therefore, was aimed to identify differentially expressed genes between clinically relevant major arteries and investigate their enrichment in endothelial dysfunction-related gene sets. A bioinformatic analysis of publicly available gene-level read counts for coronary, aortic, and tibial arteries was performed. Differential gene expression was conducted with DeSeq2 at a false discovery rate of 0.05. Differentially expressed genes were then subjected to over-representation analysis and active-subnetwork-oriented enrichment analysis, both at a false discovery rate of 0.005. Enriched terms common to both analyses were categorized for each contrast into immunity/inflammation-, membrane biology-, lipid metabolism-, and coagulation-related terms, and the top differentially expressed genes validated against Swiss Institute of Bioinformatics' Bgee database. There was mostly upregulation of differentially expressed genes for the coronary/tibial and aorta/tibial contrasts, but milder changes for the coronary/aorta contrast. Transcriptomic differences between coronary or aortic versus tibial samples largely involved immunity/inflammation-, membrane biology-, lipid metabolism-, and coagulation-related genes, suggesting potential to modulate endothelial dysfunction and atherosclerosis. These results imply atheroprone coronary and aortic environments compared with tibial artery tissue, which may explain observed relative inter-artery atherosclerosis risk.

Cadmium induces microcytosis and anisocytosis without anaemia in hypertensive rats.

Dietary cadmium (Cd2+) intake is implicated in the pathogenesis of hypertension and anaemia, but there is a paucity of information on the haematological changes in hypertensive conditions. This study, therefore, aims to evaluate the effects of Cd2+ on blood pressure (BP) and haematological indices in the Sprague-Dawley rat model. Three cohorts (n = 10 each) of control and Cd2+-fed male Sprague-Dawley rats were selected. Cd2+-exposed rats received 2.5 or 5 mg/kg b.w. cadmium chloride via gavage thrice-weekly for eight weeks, while control animals received tap water. BP and flow were measured non-invasively from rat tails twice-weekly using a CODA machine, while weights were measured thrice-weekly. Haematological indices were assessed using the Cell-Dyn Emerald Haematology Analyzer. Data were reported as mean ± SEM, and statistically analyzed using One-Way Analysis of Variance. Bonferroni post hoc test was used for multiple comparisons. Cd2+-exposure induced hypertension by significantly (p < 0.05) elevating systolic, diastolic, and mean arterial BPs, pulse pressure, and heart rate (HR), and increased (p < 0.05) blood flow. Mean cell volume (MCV) and haemoglobin (MCH) were significantly (p < 0.05) reduced, and red cell distribution width (RDW) significantly (p < 0.01) increased by exposure to 5 mg/kg b.w. Cd2+. Haemoglobin concentration (MCHC), haematocrit, haemoglobin, red blood cell, platelet, mean platelet volume, and white blood cell counts were unaffected by Cd2+-exposure. Cd2+ induced hypertension, microcytosis, hypochromicity, and anisocytosis without anaemia, which may be precursor to microcytic anaemia and coronary artery disease. This study is important in Cd2+-exposed environments and warrants further investigations.

Potency trends of cannabis in Jamaica during the period of 2014 to 2020.

Reports suggest that cannabis potency has dramatically increased over the last decade in the USA and Europe. Cannabinoids are the terpeno-phenolic compounds found in the cannabis plant and are responsible for its pharmacological activity. The two most prominent cannabinoids are delta-9-tetrahydrocannabinol (Δ9 THC) and cannabidiol (CBD). Cannabis potency is measured not only by the Δ9 THC levels but also by the ratio of Δ9 THC to other non-psychoactive cannabinoids, namely, CBD. Cannabis use was decriminalized in Jamaica in 2015, which opened the gates for the creation of a regulated medical cannabis industry in the country. To date, there is no information available on the potency of cannabis in Jamaica. In this study, the cannabinoid content of Jamaican-grown cannabis was examined over the period 2014-2020. Two hundred ninety-nine herbal cannabis samples were received from 12 parishes across the island, and the levels of the major cannabinoids were determined using gas chromatography-mass spectrometry. There was a significant increase (p < 0.05) in the median total THC levels of cannabis samples tested between 2014 (1.1%) and 2020 (10.2%). The highest median THC was detected in the central parish of Manchester (21.1%). During the period, THC/CBD ratios increased from 2.1 (2014) to 194.1 (2020), and there was a corresponding increase in the percent freshness of samples (CBN/THC ratios <0.013). The data show that a significant increase in the potency of locally grown cannabis has occurred in Jamaica during the last decade.

Country-level predictors of COVID-19 mortality.

This study aimed to identify country-level predictors of COVID-19 mortality, after controlling for diverse potential factors, and utilizing current worldwide mortality data. COVID-19 deaths, as well as geographic, demographic, socioeconomic, healthcare, population health, and pandemic-related variables, were obtained for 152 countries. Continuous variables were examined with Spearman's correlation, categorical variables with ANOVA or Welch's Heteroscedastic F Test, and country-level independent predictors of COVID-19 mortality identified by weighted generalized additive models. This study identified independent mortality predictors in six limited models, comprising groups of related variables. However, in the full model, only WHO region, percent of population ≥ 65 years, Corruption Perception Index, hospital beds/100,000 population, and COVID-19 cases/100,000 population were predictive of mortality, with model accounting for 80.7% of variance. These findings suggest areas for focused intervention in the event of similar future public health emergencies, including prioritization of the elderly, optimizing healthcare capacity, and improving deficient health sector-related governance.

A methodology for preprocessing structured big data in the behavioral sciences.

The characteristics of big data, including high volume, increased variety, and velocity, pose special challenges for data analysis. As these characteristics generally preclude manual data inspection and processing, researchers must often use computational methodologies to deal with this type of data; techniques that may be unfamiliar to nonspecialists, including behavioral scientists. However, previous data analytics methodologies within the field of computer science, developed to handle the generic tasks of data collection, preprocessing, and analysis, can be appropriated for use in other disciplines. These methodologies involve a sequential pipeline of quality checks to prepare data sets for analysis and application. Building upon these methodologies, this paper describes the Big Data Quality & Statistical Assurance (BDQSA) model, applicable for researchers in the behavioral sciences. It involves a series of data preprocessing tasks, to achieve data understanding, as well as data screening, cleaning, and transformation. These are followed by a statistical quality phase, which includes extraction of the relevant data subset, type conversions, ensuring sample representativeness when appropriate, and assessing statistical assumptions. The resulting model thereby provides methodological guidance for the preprocessing of behavioral science big data, aimed at ensuring acceptable data quality before analysis is undertaken. Sample R code snippets demonstrating the application of this model are provided throughout the paper.

Differential and targeted vesiculation: pathologic cellular responses to elevated arterial pressure.

Extracellular vesicles are small membrane-enclosed particles released during cell activation or injury. They have been investigated for several decades and found to be secreted in various diseases. Their pathogenic role is further supported by the presence of several important molecules among their cargo, including proteins, lipids, and nucleic acids. Many studies have reported enhanced and targeted extracellular vesicle biogenesis in diseases that involve chronic or transient elevation of arterial pressure resulting in endothelial dysfunction, within either the general circulatory system or specific local vascular beds. In addition, several associated pathologic processes have been studied and reported. However, the role of elevated pressure as a common pathogenic trigger across vascular domains and disease chronicity has not been previously described. This review will therefore summarize our current knowledge of the differential and targeted biogenesis of extracellular vesicles in major diseases that are characterized by elevated arterial pressure leading to endothelial dysfunction and propose a unified theory of pressure-induced extracellular vesicle-mediated pathogenesis.

Form and content of Jamaican cannabis edibles.

BACKGROUND: In 2017, the Jamaican government banned the sale of cannabis-infused edibles after reports of over-intoxication in adults and children. There is a general lack of public awareness regarding the risk involved with edible dosage. Vandrey et al. in 2015 reported that random cannabis edibles sampled from dispensaries in California and Washington in the USA failed to meet the basic labeling standards for pharmaceuticals (Vandrey et al.; JAMA 2015). This study aims to measure the levels of THC and CBD in a variety of edibles available locally in order to establish current cannabinoid content and to report on safety and packaging. This study is deemed necessary as no such study has been done to measure the potency levels of edibles and to raise awareness of the potential risk to children. METHODS: Forty-five cannabis-infused edible items were collected as convenience samples over a 4-year period (2014-2018) and analyzed. The QuEChERS technique (modified) was used to extract cannabinoids from each item. The extracts were then derivatized with MSTFA prior to analysis by gas chromatography-mass spectrometry (GC-MS). The descriptive statistics were calculated using the Statistical Package for Social Sciences-SPSS Software. Descriptive statistics presented include the mean, median, standard deviation, and range for each product category. The distribution of data with a box and whisker plot and frequency of THC to CBD ratios with a histogram was also presented. RESULTS: Edibles on the Jamaican market comprise baked goods, candies, frozen foods, and beverages. Eighty-six percent of samples were poorly labeled and failed to meet basic labeling requirements. None of the packages were observed to be child-proof. THC levels ranged from 0.01 to 99.9 mg per product while CBD levels ranged from 0.001 to 69.2 mg per product. The highest THC and CBD levels were detected in cookies and brownies. Thirty percent of the samples had THC levels greater than the recommended 10 mg THC per serving. CONCLUSION: The lack of proper labeling and the wide range of THC levels in cannabis edibles raises public health concerns for all consumers including inexperienced persons who may be at a greater risk of overdosing. Concern must also be raised over the possibility that the attractive and tasty ways in which the drug is being presented might tempt young children and teens to take cannabis. Impact statement It is hoped that this information will raise public awareness of the current potential danger these edibles pose to children and inexperienced users and that policymakers will see the need for the imposition of suitable regulations.

May Measurement Month 2019: an analysis of blood pressure screening results from Jamaica.

There is evidence of an elevated risk of hypertension in populations that are primarily of African origin. Hypertension is predominantly asymptomatic, necessitating increased awareness. May Measurement Month was a descriptive, population-based, cross-sectional study of blood pressure (BP) screening and awareness campaign conducted in 2019 in a sample of 2550 participants (≥18 years) in Jamaica. In total, 1791 (70.2%) of the participants were female, 756 (29.6%) were male, with an average age of 49.3 years, and a body mass index (kg/m2) of 28.5 (6.2). Of all participants, 2289 (89.8%) were black and 154 (6.0%) were of mixed races. Twenty-two (0.9%) had never had their BP measured, whereas 354 (13.9%) had their measurements more than a year ago, and 2129 (83.5%) had measured within the year. Of all 2550 participants, 1055 (41.4%) had hypertension, 69.9% of our subjects with hypertension were aware, whereas only 62.5% were on antihypertensive medication and 27.8% had controlled BP (systolic <140 mmHg and diastolic BP <90 mmHg). Of 660 participants on antihypertensive medication, 44.4% had controlled BP. Two hundred and seventy-six (15.4%) of women reported hypertension in a previous pregnancy. Hypertension with previous pregnancy was positively correlated with current elevation. These results suggest a high rate of raised BP among community dwellers whose hypertension had not been previously diagnosed by a health professional and warrant proactive approaches that promote community-based awareness, and regular measurements.

Cadmium-induced hypertension is associated with renal myosin light chain phosphatase inhibition via increased T697 phosphorylation and p44 mitogen-activated protein kinase levels.

Dietary intake of the heavy metal cadmium (Cd2+) is implicated in hypertension, but potassium supplementation reportedly mitigates hypertension. This study aims to elucidate the hypertensive mechanism of Cd2+. Vascular reactivity and protein expression were assessed in Cd2+-exposed rats for 8 weeks to determine the calcium-handling effect of Cd2+ and the possible signaling pathways and mechanisms involved. Cd2+ induced hypertension in vivo by significantly (p < 0.001) elevating systolic blood pressure (160 ± 2 and 155 ± 1 vs 120 ± 1 mm Hg), diastolic blood pressure (119 ± 2 and 110 ± 1 vs 81 ± 1 mm Hg), and mean arterial pressure (133 ± 2 and 125 ± 1 vs 94 ± 1 mm Hg) (SBP, DBP, and MAP, respectively), while potassium supplementation protected against elevation of these parameters. The mechanism involved augmentation of the phosphorylation of renal myosin light chain phosphatase targeting subunit 1 (MYPT1) at threonine 697 (T697) (2.58 ± 0.36 vs 1 ± 0) and the expression of p44 mitogen-activated protein kinase (MAPK) (1.78 ± 0.20 vs 1 ± 0). While acetylcholine (ACh)-induced relaxation was unaffected, 5 mg/kg b.w. Cd2+ significantly (p < 0.001) attenuated phenylephrine (Phe)-induced contraction of the aorta, and 2.5 mg/kg b.w. Cd2+ significantly (p < 0.05) augmented sodium nitroprusside (SNP)-induced relaxation of the aorta. These results support the vital role of the kidney in regulating blood pressure changes after Cd2+ exposure, which may be a key drug target for hypertension management. Given the differential response to Cd2+, it is apparent that its hypertensive effects could be mediated by myosin light chain phosphatase (MLCP) inhibition via phosphorylation of renal MYPT1-T697 and p44 MAPK. Further investigation of small arteries and the Rho-kinase/MYPT1 interaction is recommended.

Small interfering RNAs targeting agrA and sarA attenuate pathogenesis of Staphylococcus aureus in Caenorhabditis elegans.

INTRODUCTION: The use of small interfering RNA (siRNA) gene silencing is a promising therapeutic option as it does not impose selective pressure on bacteria that is often associated with the development of resistance. The study assessed the effect of siRNA targeted to sarA and agrA in S. aureus and the relationship between the transcriptional response, biofilm formation and pathogenicity. METHODOLOGY: siRNAs designed against agrA and sarA were electroporated into methicillin-resistant and methicillin-susceptible S. aureus strains. mRNA levels, growth kinetics, biofilm formation and minimal inhibitory concentration were measured. Efficacy of siRNA in bacteria was assessed using survival assays in a C. elegans model. Differences in gene expression before and after siRNA treatment were anaysed using the paired t-test, while the log rank test was used to assess the significance of any difference among survival rates of nematodes. RESULTS: Biofilm formation decreased significantly in siRNA treated strains and growth rates of siRNA treated strains were significantly higher compared to untreated strains. We observed significant decreases in the transcriptional response in siRNA treated strains, with concomitant significant increases in the lifespan of C. elegans worms exposed to siRNA-treated versus untreated strains. CONCLUSIONS: siRNA targeted to agrA and sarA lowered mRNA transcription and pathogenicity of S. aureus.

spoT-mediated stringent response influences environmental and nutritional stress tolerance, biofilm formation and antimicrobial resistance in Klebsiella pneumoniae.

Klebsiella pneumoniae is an important opportunistic pathogen with significant potential for virulence and multidrug resistance. Treatment failure often occurs because the pathogen may couple virulence and drug resistance with the stringent response. This study assessed the role of the spoT gene in environmental and nutritional stress tolerance, exopolysaccharide capsule production and biofilm formation. spoT mutants were constructed using the lambda red recombinase technique, and mutant and wild-type (WT) strains were exposed to limiting concentrations of carbon (glucose), phosphate and aminoacid, and environmental stresses of ethanol, salt and heat. Cell viability, capsule production and cell length were assessed as well as the ability to grow biofilm under antibiotic pressure using gentamicin and ceftazidime. spoT mutants were more susceptible to stresses versus WT; the reverse was true for survival during biofilm susceptibility assay (p < 0.05), especially when carbon and phosphate were present. spoT mutants were elongated and lacked a capsule versus WT and non-starved strains. The inability to produce capsule in mutants before and after starvation was likely a general effect of spoT mutation. These data suggest that the spoT-mediated stringent response is important for K. pneumoniae in conditions of nutrient limitation, environmental stress and antimicrobial pressure.

Aphis (Hemiptera, Aphididae) species living on Baccharis (Asteraceae) in southern South America, with description of three new species.

Aphid specimens belonging to the genus Aphis (Hemiptera, Aphididae, Aphidinae) collected on species of Baccharis (Asteraceae) in localities of Argentina and Chile, preserved in the Natural History Museum in London and in the Universidad de León collections, have been studied. They belong to six species: Aphis craccivora, Aphis gossypii and Aphis spiraecola, which are widely-distributed and polyphagous, and the new species: Aphis ingeborgae Nieto Nafría and Brown sp. n., Aphis conspicua Nieto Nafría and Mier Durante sp. n. and Aphis fuentesi Nieto Nafría and Ortego sp. n. which are here described from apterous and alate viviparous females, and also from oviparous females and males in the case of Aphis fuentesi. These six species plus the native and monophagous A. coridifoliae are those known in southern South America living on plants of Baccharis. Diagnostic features of new species and an identification key for apterous viviparous females of these seven species are presented.

Three new species of the genus Neuquenaphis (Hemiptera, Aphididae, Spicaphidinae) from southernmost South America.

Three new species of Neuquenaphis Blanchard are described from aphids collected in southernmost South America on several species of Nothofagus, southern beeches: Neuquenaphis blackmani Nieto Nafría and Brown, sp. n. from apterous and alate viviparous females and alatoid nymphs collected on Nothofagus dombeyi in Los Lagos and Los Ríos regions (Chile) and on Nothofagus nitida in Los Ríos region, Neuquenaphis aurata Mier Durante and von Dohlen, sp. n. from apterous and alate viviparous females collected on Nothofagus betuloides in Magallanes region (Chile) and Tierra del Fuego province (Argentina), and Neuquenaphis ramireziNieto Nafría and Ortego, sp. n. from apterous viviparous females collected on Nothofagus pumilio and N. antarctica in Tierra del Fuego province (Argentina) and La Araucanía, Aysén and Magallanes regions (Chile). Sequences of the mitochondrial COI "barcode" region and the tRNAleu-COII locus support the distinction of these new species from described Neuquenaphis species. Morphological characteristics that differentiate the new species from already described species of the genus are discussed. Partial identification keys for known apterous and alate viviparous females of Neuquenaphis species are presented on the basis of those established by Quednau (2010).

Blood Pressure Screening Campaign in Jamaica: May Measurement Month 2017.

BACKGROUND: Hypertension (HTN) is responsible for a significant disease burden in Jamaica. We are reporting the results of the 2017 blood pressure (BP) screening campaign May Measurement Month in Jamaica that aimed to increase the awareness of HTN. METHODS: Adults, 18 years old and older, from different parishes of Jamaica were invited to participate during May to June 2017. Demographic data were collected. BP, weight, and height were measured and recorded. RESULTS: Five hundred sixty-six participants (n = 566) were enrolled, 91.6% (519) from urban areas, and 72.6% (410) were females. The average age was 53.7 (18-95) years old and body mass index was 28.2 ± 6.6 kg/m2. The prevalence of HTN was 47.3% (267/566), without gender or living areas differences (both P > 0.1). Prevalence of HTN was lower in those who self-identified as Interracial ethnicity, in comparison with Afro-Caribbean (33% vs. 48.3%; P = 0.04). About third of the hypertensive patients were not aware of the high BP (89/267; 35.6%). Between hypertensive patients, 64.4% (172/267) were receiving antihypertensive drugs. The rate of BP control was 32% of the hypertensive patients and 50% of those receiving antihypertensive medication. Significant lower BP control was observed between diabetic vs. nondiabetic patients (34.3% vs. 60%; P < 0.001). CONCLUSION: We found a high prevalence of HTN in this population, especially in patients with diabetes or previous cardiovascular diseases. We report an increase in HTN awareness in Jamaica but more advances need to be performed to increase HTN treatment and control.

Two new species of the genus Aphis (Hemiptera, Aphididae) from Chile on host species of Alstroemeriaceae and Ericaceae.

Specimens from Southern Chile belonging to two undescribed aphid species held at the Natural History Museum in London have been studied. Aphis luzuriagaesp. n. collected on Luzuriaga radicans and on other unidentified Luzuriaga species (Alstroemeriaceae) is described from apterous and alate viviparous females. Aphis gaultheriaesp. n. collected on Gaultheria mucronata (Ericaceae) is described from apterous viviparous females. Taxonomic peculiarities of both species are discussed.

Temperature and Oxidative Stress as Triggers for Virulence Gene Expression in Pathogenic Leptospira spp.

Leptospirosis is a zooanthroponosis aetiologically caused by pathogenic bacteria belonging to the genus, Leptospira. Environmental signals such as increases in temperatures or oxidative stress can trigger response regulatory modes of virulence genes during infection. This study sought to determine the effect of temperature and oxidative stress on virulence associated genes in highly passaged Leptospira borgpeterseneii Jules and L. interrogans Portlandvere. Bacteria were grown in EMJH at 30°C, 37°C, or at 30°C before being transferred to 37°C. A total of 14 virulence-associated genes (fliY, invA, lenA, ligB, lipL32, lipL36, lipL41, lipL45, loa22, lsa21, mce, ompL1, sph2, and tlyC) were assessed using endpoint PCR. Transcriptional analyses of lenA, lipL32, lipL41, loa22, sph2 were assessed by quantitative real-time RT-PCR at the temperature conditions. To assess oxidative stress, bacteria were exposed to H2O2 for 30 and 60 min with or without the temperature stress. All genes except ligB (for Portlandvere) and ligB and mce (for Jules) were detectable in the strains. Quantitatively, temperature stress resulted in significant changes in gene expression within species or between species. Temperature changes were more influential in gene expression for Jules, particularly at 30°C and upshift conditions; at 37°C, expression levels were higher for Portlandvere. However, compared to Jules, where temperature was influential in two of five genes, temperature was an essential element in four of five genes in Portlandvere exposed to oxidative stress. At both low and high oxidative stress levels, the interplay between genetic predisposition (larger genome size) and temperature was biased towards Portlandvere particularly at 30°C and upshift conditions. While it is clear that expression of many virulence genes in highly passaged strains of Leptospira are attenuated or lost, genetic predisposition, changes in growth temperature and/or oxidative intensity and/or duration were factors which acted in isolation or together with other regulatory cues to contribute to the variable gene expression observed in this study. Overall, differential gene expression in serovar Portlandvere was more responsive to temperature and oxidative stress.

Aphis species (Hemiptera, Aphididae) living on Mulinum (Apiaceae) in South America, with a description of a new species.

Aphis species living on the South American native genus Mulinum are studied. Aphis vurilocensis Nieto Nafría, Brown and López Ciruelos, sp. n. is described from apterous viviparous females. Alate viviparous females, oviparous females and winged males of Aphis roberti are described. Knowledge of intraspecific variability of apterous viviparous females of A. martinezi, A. paravanoi and A. roberti is developed. An identification key of apterous viviparous females of Aphis species living on Mulinum is presented.

Association between the agr locus and the presence of virulence genes and pathogenesis in Staphylococcus aureus using a Caenorhabditis elegans model.

BACKGROUND: Staphylococcus aureus is a commensal pathogen with a virulon that is under agr control. agr dysfunction has been seen in clinical strains that do not respond positively to treatment. This study aimed to establish the association between the genes in the virulon and the presence of agr and to determine the relationship between the presence or absence of agr and pathogenicity. METHODS: PCR was used to identify the presence of the agr operon in 101 clinical S. aureus strains. δ-Haemolysin screening was conducted on all agr-positive strains using the blood agar assay. Singleplex and/or multiplex PCR was used to determine the presence of 31 virulence genes in the strains. Caenorhabditis elegans infectivity and lifespan assays were conducted using 30 CF512 nematodes per strain in triplicate. Significance associated with the carriage of virulence and agr genes was determined using the Chi-square test. Nematode survival was measured using Kaplan-Meier survival estimates and differences in survival were assessed using the log-rank test. RESULTS: The frequency of agr-negative strains was 20%. All groups of virulence genes were significantly associated with agr-positive strains: enterotoxin (p<0.001), toxins (p<0.001), capsule (p=0.036), and microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) (p=0.0026). The median lifespan (q=0.5) of agr-negative strains was 15.5 days and of agr-positive strains was 6.5 days. The log-rank test showed a significant difference in the survival rate of nematodes exposed to the two groups (p=0.006). CONCLUSIONS: There was a strong association between the carriage of virulence genes and the presence of the agr operon in clinical strains of S. aureus. Further, agr-positive strains were more pathogenic than agr-negative strains, suggesting a correlation between the presence of agr, carriage of virulence determinants, and pathogenicity.

Epigenetic Influence of Dam Methylation on Gene Expression and Attachment in Uropathogenic Escherichia coli.

Urinary tract infections (UTI) are among the most frequently encountered infections in clinical practice globally. Predominantly a burden among female adults and infants, UTIs primarily caused by uropathogenic Escherichia coli (UPEC) results in high morbidity and fiscal health strains. During pathogenesis, colonization of the urinary tract via fimbrial adhesion to mucosal cells is the most critical point in infection and has been linked to DNA methylation. Furthermore, with continuous exposure to antibiotics as the standard therapeutic strategy, UPEC has evolved to become highly adaptable in circumventing the effect of antimicrobial agents and host defenses. Hence, the need for alternative treatment strategies arises. Since differential DNA methylation is observed as a critical precursor to virulence in various pathogenic bacteria, this body of work sought to assess the influence of the DNA adenine methylase (dam) gene on gene expression and cellular adhesion in UPEC and its potential as a therapeutic target. To monitor the influence of dam on attachment and FQ resistance, selected UPEC dam mutants created via one-step allelic exchange were transformed with cloned qnrA and dam complement plasmid for comparative analysis of growth rate, antimicrobial susceptibility, biofilm formation, gene expression, and mammalian cell attachment. The absence of DNA methylation among dam mutants was apparent. Varying deficiencies in cell growth, antimicrobial resistance and biofilm formation, alongside low-level increases in gene expression (recA and papI), and adherence to HEK-293 and HTB-9 mammalian cells were also detected as a factor of SOS induction to result in increased mutability. Phenotypic characteristics of parental strains were restored in dam complement strains. Dam's vital role in DNA methylation and gene expression in local UPEC isolates was confirmed. Similarly to dam-deficient Enterohemorrhagic E. coli (EHEC), these findings suggest unsuccessful therapeutic use of Dam inhibitors against UPEC or dam-deficient UPEC strains as attenuated live vaccines. However, further investigations are necessary to determine the post-transcriptional influence of dam on the regulatory network of virulence genes central to pathogenesis.