Infectious Disease Resistance Research Articles

Unveiling the Chemical Constituents and Inhibitory Roles of Extracts from Pinus Pinea L. Nut and Nutshell: A Novel Source for Pharmaceutical Antimicrobials.

Antibiotic resistance in infectious diseases has been a serious problem for the last century, and scientists have focused on discovering new natural antimicrobial agents. Pinus pinea has been used as a natural pharmacotherapeutic agent with antimutagenic, anticarcinogenic, and high antioxidant properties. In this study, GC-MS and LC-HR/MS were employed to analyze Pinus pinea L. nut and nutshell extracts. DPPH radical scavenging assay was performed to analyze the antioxidant properties of the extracts, but no activity was determined. GC-MS analysis showed that linoleic, oleic, and palmitic acids were the three most dominant fatty acids in nut and nutshell extracts, with ratios between 6.75 % and 47.06 % (v/v). LC-HR/MS revealed that the nutshell methanol extract had a higher phenolic content than other extracts, with vanillic acid (1.4071 mg/g). Antimicrobial activity assays showed that the minimum inhibitory concentrations (MIC) of the extracts varied between 5.94 and 190 mg/mL, and the most significant inhibition was seen in the nutshell methanol extract (MICs: between 5.94 and 47.5 mg/mL). Consequently, the antimicrobial activity of the extracts can be attributed to the dense fatty acids they contain, and the nutshell methanol extract showed the most potent inhibition related to the abundance of phenolic compounds in the extract.

Biological Activity of Complexes Involving Nitro-Containing Ligands and Crystallographic-Theoretical Description of 3,5-DNB Complexes.

Drug resistance in infectious diseases developed by bacteria and fungi is an important issue since it is necessary to further develop novel compounds with biological activity that counteract this problem. In addition, new pharmaceutical compounds with lower secondary effects to treat cancer are needed. Coordination compounds appear to be accessible and promising alternatives aiming to overcome these problems. In this review, we summarize the recent literature on coordination compounds based on nitrobenzoic acid (NBA) as a ligand, its derivatives, and other nitro-containing ligands, which are widely employed owing to their versatility. Additionally, an analysis of crystallographic data is presented, unraveling the coordination preferences and the most effective crystallization methods to grow crystals of good quality. This underscores the significance of elucidating crystalline structures and utilizing computational calculations to deepen the comprehension of the electronic properties of coordination complexes.

A simulated natural heatwave perturbs bumblebee immunity and resistance to infection.

As a consequence of ongoing climate change, heatwaves are predicted to increase in frequency, intensity, and duration in many regions. Such extreme events can shift organisms from thermal optima for physiology and behaviour, with the thermal stress hypothesis predicting reduced performance at temperatures where the maintenance of biological functions is energetically costly. Performance includes the ability to resist biotic stressors, including infectious diseases, with increased exposure to extreme temperatures having the potential to synergise with parasite infection. Climate change is a proposed threat to native bee pollinators, directly and through indirect effects on floral resources, but the thermal stress hypothesis, particularly pertaining to infectious disease resistance, has received limited attention. We exposed adult Bombus impatiens bumblebee workers to simulated, ecologically relevant heatwave or control thermal regimes and assessed longevity, immunity, and resistance to concurrent or future parasite infections. We demonstrate that survival and induced antibacterial immunity are reduced following heatwaves. Supporting that heatwave exposure compromised immunity, the cost of immune activation was thermal regime dependent, with survival costs in control but not heatwave exposed bees. However, in the face of real infections, an inability to mount an optimal immune response will be detrimental, which was reflected by increased trypanosomatid parasite infections following heatwave exposure. These results demonstrate interactions between heatwave exposure and bumblebee performance, including immune and infection outcomes. Thus, the health of bumblebee pollinator populations may be affected through altered interactions with parasites and pathogens, in addition to other effects of extreme manifestations of climate change.

Recent Advances in Colorimetric Tests for the Detection of Infectious Diseases and Antimicrobial Resistance.

Diagnosis of infection-causing microorganisms with sensitive, rapid, selective and economical diagnostic tests is critical to start the right treatment. With these tests, the spread of infections can be prevented. In addition to that, the detection of antimicrobial resistance also makes a significant contribution to public health. In recent years, different types of diagnostic tests have been developed as alternatives to traditional diagnostic tests used in clinics. In particular, colorimetric tests, which minimize the need for an instrument, have advantages owing to their cost effectiveness, rapid response and naked-eye detection and practical use. In this review, we especially focused on pH indicators and nanomaterial-based colorimetric tests in detection of infection-causing microorganisms and antimicrobial resistance.

CRISPR-Cas-Based Antimicrobials: Design, Challenges, and Bacterial Mechanisms of Resistance.

The emergence of antibiotic-resistant bacterial strains is a source of public health concern across the globe. As the discovery of new conventional antibiotics has stalled significantly over the past decade, there is an urgency to develop novel approaches to address drug resistance in infectious diseases. The use of a CRISPR-Cas-based system for the precise elimination of targeted bacterial populations holds promise as an innovative approach for new antimicrobial agent design. The CRISPR-Cas targeting system is celebrated for its high versatility and specificity, offering an excellent opportunity to fight antibiotic resistance in pathogens by selectively inactivating genes involved in antibiotic resistance, biofilm formation, pathogenicity, virulence, or bacterial viability. The CRISPR-Cas strategy can enact antimicrobial effects by two approaches: inactivation of chromosomal genes or curing of plasmids encoding antibiotic resistance. In this Review, we provide an overview of the main CRISPR-Cas systems utilized for the creation of these antimicrobials, as well as highlighting promising studies in the field. We also offer a detailed discussion about the most commonly used mechanisms for CRISPR-Cas delivery: bacteriophages, nanoparticles, and conjugative plasmids. Lastly, we address possible mechanisms of interference that should be considered during the intelligent design of these novel approaches.

Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.

Near-Infrared Copper Sulfide Hollow Nanostructures with Enhanced Photothermal and Photocatalytic Performance for Effective Bacterial Sterilization.

The development of nonantibiotic strategies to combat bacterial infection is highly needed, owing to the widespread infectious disease and bacterial resistance becoming a significant health threat to the world's population. In recent years, photoactivated antibacterial therapies including photocatalytic and photothermal therapies have attracted increasing attention due to their high efficiency and low side effect. Herein, we introduce a copper sulfide (Cu2-xS) hollow nanostructure-based near-infrared antibacterial platform with synergy photothermal and photocatalytic properties for effective bacterial sterilization. Compared to traditional Cu2-xS nanoparticles, this unique hollow Cu2-xS nanostructure can generate multiple scattered light, which is conducive to light collection. Moreover, its thin shell can shorten the transmission distance of carrier, thus reducing the charge recombination that usually causes the greatest energy loss. As a result, such a Cu2-xS hollow nanostructure enables enhanced photothermal and photocatalytic bacterial killing activities against both Escherichia coli and Staphylococcus aureus, showing promise for antibiotic-free infection treatment and other bacterial sterilization applications.

The Application of Nanoparticle-Based Imaging and Phototherapy for Female Reproductive Organs Diseases.

Various female reproductive disorders affect millions of women worldwide and bring many troubles to women's daily life. Let alone, gynecological cancer (such as ovarian cancer and cervical cancer) is a severe threat to most women's lives. Endometriosis, pelvic inflammatory disease, and other chronic diseases-induced pain have significantly harmed women's physical and mental health. Despite recent advances in the female reproductive field, the existing challenges are still enormous such as personalization of disease, difficulty in diagnosing early cancers, antibiotic resistance in infectious diseases, etc. To confront such challenges, nanoparticle-based imaging tools and phototherapies that offer minimally invasive detection and treatment of reproductive tract-associated pathologies are indispensable and innovative. Of late, several clinical trials have also been conducted using nanoparticles for the early detection of female reproductive tract infections and cancers, targeted drug delivery, and cellular therapeutics. However, these nanoparticle trials are still nascent due to the body's delicate and complex female reproductive system. The present review comprehensively focuses on emerging nanoparticle-based imaging and phototherapies applications, which hold enormous promise for improved early diagnosis and effective treatments of various female reproductive organ diseases.

What\'s New about Antimicrobial Resistance in Pediatric Infectious Diseases?

What\'s New about Antimicrobial Resistance in Pediatric Infectious Diseases?

Yeni Piridin Bazlı N-Açil Hidrazon Türevlerinin Sentezi ve Spektroskopik Karakterizasyonu ve Glukozamin-6-Fosfat Üzerine Moleküler Yerleştirme Çalışmaları

Antimicrobial resistance in infectious diseases caused by organisms such as bacteria, fungi, viruses, and parasites has led to an increase in studies and demands for new antimicrobial drug development. The compounds including pyridine and N-acylhydrazone skeletons in their structures have a large application area in drug discovery due to their anticancer, anti-tubercular, anti-bacterial and anti-fungal activities. Here, the novel N-acyl-hydrazone derivatives, (E)-2-oxo-N'-(2,3,4-trimethoxybenzylidene)-1,2-dihydropyridine-3-carbohydrazide and (E)-N'-(1-(4-bromophenyl) ethylidene)-2-oxo-1,2-dihydropyridine-3-carbohydrazide were synthesized through a multistep reaction sequence. The structures of newly synthesized compounds were established on the basis of IR, 1D and 2D NMR spectra and mass spectral data. The theoretical electronic structure analysis was performed by density functional theory (DFT) at the B3LYP level with the 6-311++G(d,p) basis set in the gas phase of synthesized compounds. The newly synthesized compounds were docked on glucosamine-6 phosphate synthase to determine potential interactions between the analyzed compounds and its active site due to its role in microbial cell wall synthesis. The possibilities of these compounds to being active for antimycobacterial and antituberculosis have been found as quite high, and their interactions in the binding site have been determined with the range of binding affinity, [-7.1, -7.3] kcal/mol, respectively.

1295. Cross-sectional survey on education of clinical infectious diseases and antimicrobial resistance in pharmaceutical department in Japanese universities

Abstract Background Pharmacists play an important role in infection control and antimicrobial stewardship teams in hospitals and the community. The need for education on antimicrobial resistance (AMR) and clinical infectious diseases (CID) is increasing. However, the status of Japanese pharmaceutical education on CID and AMR is unclear. Methods We conducted a nationwide cross-sectional survey of pharmaceutical department in Japanese universities between February and March 2022. Data on the following were collected using questionnaires: 1) basic information; 2) number of faculty members with experience in CID; 3) lecture times for CID and AMR; 4) self-evaluation of CID and AMR education; and 5) the most important issues in CID and AMR education. Descriptive analyses were conducted. Results Among the 74 participating universities, 44 (59.5%) universities responded. The median number [IQR] of faculties of infectious disease education was 7 [4–12], and clinical faculties was 3 [1–6]. Twenty-seven (62.8%) of the universities had faculties with clinical experience in infectious diseases. Lectures time for CID and AMR varied among the universities. Respondents indicated that CID and AMR lectures were insufficient, compared to microbiology basic lectures. Additionally, insufficient lecture time and specialists were the most common responses as the most important issues in CID and AMR education. University background and questions regarding CID and AMR lectures (N=44) Boxplot of lectures time for clinical infectious disease and antimicrobial resistance education Self-evaluation of clinical infectious disease and antimicrobial resistance education Conclusion This study revealed that educational status and resources for CID and AMR education varied widely, and that practical lectures on CID and AMR may be insufficient. We suggest that the entire core curriculum and resources, including the number of faculties, needs to be examined and improved. The most important issues in clinical infectious disease and antimicrobial resistance education. Disclosures All Authors: No reported disclosures.

Ultrasensitive Detection of Multidrug-Resistant Mycobacterium tuberculosis Using SuperSelective Primer-Based Real-Time PCR Assays

The emergence of drug-resistant tuberculosis is a significant global health issue. The presence of heteroresistant Mycobacterium tuberculosis is critical to developing fully drug-resistant tuberculosis cases. The currently available molecular techniques may detect one copy of mutant bacterial genomic DNA in the presence of about 1-1000 copies of wild-type M. tuberculosis DNA. To improve the limit of heteroresistance detection, we developed SuperSelective primer-based real-time PCR assays, which, by their unique assay design, enable selective and exponential amplification of selected point mutations in the presence of abundant wild-type DNA. We designed SuperSelective primers to detect genetic mutations associated with M. tuberculosis resistance to the anti-tuberculosis drugs isoniazid and rifampin. We evaluated the efficiency of our assay in detecting heteroresistant M. tuberculosis strains using genomic DNA isolated from laboratory strains and clinical isolates from the sputum of tuberculosis patients. Results show that our assays detected heteroresistant mutations with a specificity of 100% in a background of up to 104 copies of wild-type M. tuberculosis genomic DNA, corresponding to a detection limit of 0.01%. Therefore, the SuperSelective primer-based RT-PCR assay is an ultrasensitive tool that can efficiently diagnose heteroresistant tuberculosis in clinical specimens and contributes to understanding the drug resistance mechanisms. This approach can improve the management of antimicrobial resistance in tuberculosis and other infectious diseases.

Racial/Ethnic Differences in Sexually Transmitted Infection Testing Among Transgender Men and Nonbinary Assigned Female at Birth Young Adults in the United States: a National Study.

Sexually transmitted infections (STIs) cause a major burden of disease in the United States (US)-especially among structurally marginalized populations, including transgender and nonbinary people, individuals assigned female at birth (AFAB), Black and Latinx/e individuals, and young adults. Although screening can help detect and prevent STIs, research on STI testing among populations at diverse intersections of multiple forms of structural marginalization, including Black, Latinx/e, and other racially/ethnically minoritized transgender men and nonbinary AFAB US young adults, is extremely scarce. We conducted a national cross-sectional online survey of transgender and nonbinary US young adults from February to July 2019. Using Poisson regression, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) for the associations between race/ethnicity-which we conceptualized as a system of structural inequality that shapes individuals' and groups' exposure to racism-and lifetime and past-year STI testing among transgender men and nonbinary AFAB US young adults aged 18-30years with at least one-lifetime sexual partner (N = 378). Approximately 74% of participants had received an STI test in their lifetime, and, among those, 72% with a past-year sexual partner had been tested for an STI in the last 12months. We observed no statistically significant association between race/ethnicity and lifetime STI testing among transgender and nonbinary AFAB young adults with a lifetime sexual partner. In contrast, Black (PR = 1.32; 95%: 1.03, 1.68) and Latinx/e (PR = 1.39; 95% CI: 1.11, 1.75) transgender men and nonbinary AFAB young adults who ever received an STI test and had a past-year sexual partner were significantly more likely to have received an STI test in the last 12months relative to their White counterparts, adjusting for demographic factors. Further adjustment for lifetime STI diagnosis and health insurance status did not appreciably attenuate these observed adjusted differences; however, the adjusted difference in the prevalence of past-year STI testing between Black (but not Latinx/e) and White transgender men and nonbinary AFAB young adults was no longer statistically significant upon further adjustment for educational attainment and employment status, possibly due to small sample sizes. The higher adjusted prevalence of past-year STI testing among Black and Latinx/e compared to White transgender men and nonbinary AFAB US young adults may reflect racist and xenophobic sexual stereotypes about Black and Latinx/e people among health care providers and institutions, the history of hyper-surveillance of Black and Latinx/e people by public health institutions in the context of infectious disease containment, and/or agency and resistance among Black and Latinx/e transgender men and nonbinary AFAB young adults with regard to sexual health promotion in the face of multiple compounding systems of oppression.

HSD60 TRENDSTM Knowledge and Attitudes of Pharmacists Regarding Infectious Diseases and Antimicrobial Resistance in Hungary: Questionnaire-Development, Validation and a Quantitative, Cross-Sectional Study

HSD60 TRENDSTM Knowledge and Attitudes of Pharmacists Regarding Infectious Diseases and Antimicrobial Resistance in Hungary: Questionnaire-Development, Validation and a Quantitative, Cross-Sectional Study

What Can Genetics Do for the Control of Infectious Diseases in Aquaculture?

Simple SummaryInfectious diseases place an economic burden on aquaculture and a limitation to its growth. This state-of-the-art review describes the application of genetics and genomics as novel tools to control infectious disease in aquaculture.Infectious diseases place an economic burden on aquaculture and a limitation to its growth. An innovative approach to mitigate their impact on production is breeding for disease resistance: selection for domestication, family-based selection, marker-assisted selection, and more recently, genomic selection. Advances in genetics and genomics approaches to the control of infectious diseases are key to increasing aquaculture efficiency, profitability, and sustainability and to reducing its environmental footprint. Interaction and co-evolution between a host and pathogen can, however, turn breeding to boost infectious disease resistance into a potential driver of pathogenic change. Parallel molecular characterization of the pathogen and its virulence and antimicrobial resistance genes is therefore essential to understand pathogen evolution over time in response to host immunity, and to apply appropriate mitigation strategies.

Characterization Of Phyto-Synthesized Silver Nanoparticles And Their Antimicrobial Activity Against Diabetic Foot Ulcer Bacterial Isolates.

Diabetic Foot Ulcer (DFU) is one of the major complications of Diabetes. Patients with Diabetic Foot ulcers have a high susceptibility to microbial infections and are the leading cause of hospitalization and amputation of lower limbs. In the era of increased prevalence of bacterial resistance and outbreak of resistant infectious diseases, it is very essential to develop effective therapeutic strategies towards multi-drug resistant pathogens. The antimicrobial properties of silver nanoparticles have been well studied, therefore their use in biomedicine and pharmacology is a trend. Herein we present the use of Phyto-mediated synthesized AgNPs for the treatment of diabetic foot ulcers by topical administration. The nanoparticles were synthesized by reducing silver nitrate using Terminalia chebula fruit extract. The nanoparticles were analyzed and characterized using UV-Visible Spectrophotometer, FTIR, XRD, SEM with EDAX, TEM, and DLS. The synthesized silver nanoparticles were assayed for antimicrobial activity against five Diabetic Foot Ulcer bacterial isolates i.e. Escherichia coli, Klebsiella Pneumoniae, Pseudomonas aeruginosa, Streptococcus aureus, and Bacillus subtilis. The bactericidal property of synthesized nanoparticles was analyzed by the Agar well diffusion method, which revealed the remarkable antimicrobial effects against all the selective pathogenic bacterial isolates of Diabetic foot ulcers in the present study. These results constituted the basis for further studies on the use of plant-based silver nanoparticles for the treatment of Diabetic Foot ulcers from different origins.

One-step base editing in multiple genes by direct embryo injection for pig trait improvement.

The precise and simultaneous acquisition of multiple beneficial alleles in the genome is in great demand for the development of elite pig breeders. Cytidine base editors (CBEs) that convert C:G to T:A have emerged as powerful tools for single-nucleotide replacement. Whether CBEs can effectively mediate C-to-T substitution at multiple sites/loci for trait improvement by direct zygote injection has not been verified in large animals. Here, we determined the editing efficiency of four CBE variants in porcine embryonic fibroblast cells and embryos. The findings showed that hA3A-BE3-Y130F and hA3A-eBE-Y130F consistently resulted in increased base-editing efficiency and low toxic effects in embryonic development. Further, we verified that using a one-step approach, direct zygote microinjection of the CBE system can generate pigs harboring multiple point mutations. Our process resulted in a stop codon in CD163 and myostatin (MSTN) and introduced a beneficial allele in insulin-like growth factor-2 (IGF2). The pigs showed disrupted expression of CD163 and MSTN and increased expression of IGF2, which significantly improved growth performance and infectious disease resistance. Our approach allows immediate introduction of multiple mutations in transgene-free animals to comprehensively improve economic traits through direct embryo microinjection, providing a potential new route to produce elite pig breeders.

Antibiotics Sensitivity of Escherichia coli to Different Concentrations of Combined Herbal Drugs

Background: The use of combinational approach in chemotherapeutic management has proven more effective against infectious disease and lower resistance development but the untoward effect of this is yet to be explored for alternative medicine.
 Aims: This study aimed to study the effect of a combinational approach of herbal drugs on Escherichia coli response.
 Methods: E. coli was treated in different concentrations of combined herbal drugs (Beta herbal drugs and Deep root herbal mixture – BD) and (Beta herbal drug and Goko cleanser – BG). The different concentrations of the mixtures employed were: 33.3%, 11.1%, 3.7%, 1.2% and 0.4%. The bacteria concentration of 103 CFU/ml was treated in the different concentrations of the herbal drugs. The growth response of the cultures were analyzed at 24 and 48 hrs. The antibiotic sensitivity of the bacteria exposed to the herbal drugs were measured against perfloxacin (PEF), ciprofloxacin (CIP), streptomycin (S), and septrin (SEP).
 Results: The growth response curve showed growth of E. coli peaked in the lower concentrations but levelled down in the higher concentrations. 24 hr growth conditions showed much higher growth level than 48 hr. Higher concentrations of BG drug combination showed higher zones of clearance and only one concentration showed resistance: 0.4% (CIP). There was no unique pattern seen in the sensitivity of E. coli treated with BD however, there was five (5) cases of complete resistance: 0.4% (PEF), 1.2% (PEF) and 11.1% (CIP and SEP).
 Conclusion: In vitro, the combined herbal drugs do not completely eliminate E. coli. However, some concentrations of the combinations demonstrated complete resistance to the antibiotics which shows that these locally made antimicrobial could confer antibiotic resistance to E. coli.

Skin bacterial metacommunities of San Francisco Bay Area salamanders are structured by host genus and habitat quality.

Host-associated microbial communities can influence physiological processes of macroorganisms, including contributing to infectious disease resistance. For instance, some bacteria that live on amphibian skin produce antifungal compounds that inhibit two lethal fungal pathogens, Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). Therefore, differences in microbiome composition among host species or populations within a species can contribute to variation in susceptibility to Bd/Bsal. This study applies 16S rRNA sequencing to characterize the skin bacterial microbiomes of three widespread terrestrial salamander genera native to the western United States. Using a metacommunity structure analysis, we identified dispersal barriers for these influential bacteria between salamander families and localities. We also analysed the effects of habitat characteristics such as percent natural cover and temperature seasonality on the microbiome. We found that certain environmental variables may influence the skin microbial communities of some salamander genera more strongly than others. Each salamander family had a somewhat distinct community of putative anti-Bd skin bacteria, suggesting that salamanders may select for a functional assembly of cutaneous symbionts that could differ in its ability to protect these amphibians from disease. Our observations raise the need to consider host identity and environmental heterogeneity during the selection of probiotics to treat wildlife diseases.

Decades of emerging infectious disease, food safety, and antimicrobial resistance response in Vietnam: The role of One Health

Since facing outbreaks of severe acute respiratory syndrome and avian influenza A in 2003, Vietnam has increasingly applied a One Health approach to address emerging infectious diseases of animal origin. Here, we reflect on the challenges and opportunities of One Health in the context of zoonoses, food safety, and antimicrobial resistance, drawing on a stocktake of One Health training, policy, and research in Vietnam. We also report on the results of a virtual consultation workshop held on July 2021 with representatives from 32 institutions in Vietnam to explore future One Health directions. As Vietnam approaches nearly two decades of disease preparedness and response, we hope our experiences can provide practical insights to support countries in developing coordination mechanisms and moving the One Health agenda forward toward better public health outcomes.