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Methods in Molecular Biology (Clifton,... 2024The emergence of zoonotic viruses like severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2...
The emergence of zoonotic viruses like severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 have significantly impacted global health and economy. The discovery of other viruses in wildlife reservoir species present a threat for future emergence in humans and animals. Therefore, assays that are less reliant on virus-specific information, such as neutralization assays, are crucial to rapidly develop diagnostics, understand virus replication and pathogenicity, and assess the efficacy of therapeutics against newly emerging viruses. Here, we describe the discontinuous median tissue culture infectious dose 50 (TCID) assay to quantitatively determine the titer of any virus that can produce a visible cytopathic effect in infected cells.
Topics: Animals; Humans; Cytopathogenic Effect, Viral; SARS-CoV-2; Chlorocebus aethiops; COVID-19; Vero Cells; Virus Replication; Tissue Culture Techniques
PubMed: 38888774
DOI: 10.1007/978-1-0716-3890-3_8 -
Journal of Environmental Health Science... Jun 2024Landfill leachate contains antibiotic resistance genes (ARGs) and microplastics (MPs), making it an important reservoir. However, little research has been conducted on... (Review)
Review
Landfill leachate contains antibiotic resistance genes (ARGs) and microplastics (MPs), making it an important reservoir. However, little research has been conducted on how ARGs are enriched on MPs and how the presence of MPs affects pathogens and ARGs in leachates and soil. MPs possess the capacity to establish unique bacterial populations and assimilate contaminants from their immediate surroundings, generating a potential environment conducive to the growth of disease-causing microorganisms and antibiotic resistance genes (ARGs), thereby exerting selection pressure. Through a comprehensive analysis of scientific literature, we have carried out a practical assessment of this topic. The gathering of pollutants and the formation of dense bacterial communities on microplastics create advantageous circumstances for an increased frequency of ARG transfer and evolution. Additional investigations are necessary to acquire a more profound comprehension of how pathogens and ARGs are enriched, transported, and transferred on microplastics. This research is essential for evaluating the health risks associated with human exposure to these pollutants.
PubMed: 38887766
DOI: 10.1007/s40201-023-00879-6 -
European Journal of Pharmaceutics and... Jun 2024The latent reservoir of human immunodeficiency virus (HIV) is a major obstacle in the treatment of acquired immune deficiency syndrome (AIDS). The "shock and kill"...
The latent reservoir of human immunodeficiency virus (HIV) is a major obstacle in the treatment of acquired immune deficiency syndrome (AIDS). The "shock and kill" strategy has emerged as a promising approach for clearing HIV latent reservoirs. However, current latency-reversing agents (LRAs) have limitations in effectively and safely activating the latent virus and reducing the HIV latent reservoirs in clinical practice. Previously, EK-16A was extracted from Euphorbia kansui, which had the effect of interfering with the HIV-1 latent reservoir and inhibiting HIV-1 entry. Nevertheless, there is no suitable and efficient EK-16A oral formulation for in vivo delivery and clinical use. In this study, an oral EK-16A self-nanoemulsifying drug delivery system (EK-16A-SNEDDS) was proposed to "shock" the HIV-1 latent reservoir. This system aims to enhance the bioavailability and delivery of EK-16A to various organs. The composition of EK-16A-SNEDDS was optimized through self-emulsifying grading and ternary phase diagram tests. Cell models, pharmacokinetic experiments, and pharmacodynamics in HIV-1 latent cell transplant animal models suggested that EK-16A-SNEDDS could be absorbed by the gastrointestinal tract and enter the blood circulation after oral administration, thereby reaching various organs to activate latent HIV-1. The prepared EK-16A-SNEDDS demonstrated safety and efficacy, exhibited high clinical experimental potential, and may be a promising oral preparation for eliminating HIV-1 latent reservoirs.
PubMed: 38885911
DOI: 10.1016/j.ejpb.2024.114353 -
Methods in Molecular Biology (Clifton,... 2024Establishing a biofilm infection model in vivo allows a better understanding of the underlying infection mechanisms of bacteria. Here we describe a method for...
Establishing a biofilm infection model in vivo allows a better understanding of the underlying infection mechanisms of bacteria. Here we describe a method for constructing an in vivo biofilm model of Streptococcus suis. The animal modeled is a piglet, which is the natural reservoir of S. suis, and the mode of clinical infection is simulated by intranasal inoculation of S. suis. This model is in line with clinical practice, easy to operate, and has good repeated stability.
Topics: Biofilms; Animals; Streptococcus suis; Swine; Streptococcal Infections; Disease Models, Animal
PubMed: 38884908
DOI: 10.1007/978-1-0716-3898-9_3 -
Research Square Jun 2024Antiretroviral therapy (ART) improves the quality of life for those living with the human immunodeficiency virus type one (HIV-1). However, poor compliance reduces ART...
Antiretroviral therapy (ART) improves the quality of life for those living with the human immunodeficiency virus type one (HIV-1). However, poor compliance reduces ART effectiveness and leads to immune compromise, viral mutations, and disease co-morbidities. A novel drug formulation is made whereby a lipid nanoparticle (LNP) carrying rilpivirine (RPV) is decorated with the C-C chemokine receptor type 5 (CCR5). This facilitates myeloid drug depot deposition. Particle delivery to viral reservoirs is tracked by positron emission tomography. The CCR5-mediated RPV LNP cell uptake and retention reduce HIV-1 replication in human monocyte-derived macrophages and infected humanized mice. Focused ultrasound allows the decorated LNP to penetrate the blood-brain barrier and reach brain myeloid cells. These findings offer a role for CCR5-targeted therapeutics in antiretroviral delivery to optimize HIV suppression.
PubMed: 38883780
DOI: 10.21203/rs.3.rs-4433306/v1 -
IMeta Apr 2024The infant gut microbiome is increasingly recognized as a reservoir of antibiotic resistance genes, yet the assembly of gut resistome in infants and its influencing...
The infant gut microbiome is increasingly recognized as a reservoir of antibiotic resistance genes, yet the assembly of gut resistome in infants and its influencing factors remain largely unknown. We characterized resistome in 4132 metagenomes from 963 infants in six countries and 4285 resistance genes were observed. The inherent resistome pattern of healthy infants ( = 272) could be distinguished by two stages: a multicompound resistance phase (Months 0-7) and a tetracycline-mupirocin-β-lactam-dominant phase (Months 8-14). Microbial taxonomy explained 40.7% of the gut resistome of healthy infants, with (25.5%) harboring the most resistance genes. In a further analysis with all available infants ( = 963), we found age was the strongest influencer on the resistome and was negatively correlated with the overall resistance during the first 3 years ( < 0.001). Using a random-forest approach, a set of 34 resistance genes could be used to predict age ( = 68.0%). Leveraging microbial host inference analyses, we inferred the age-dependent assembly of infant resistome was a result of shifts in the gut microbiome, primarily driven by changes in taxa that disproportionately harbor resistance genes across taxa (e.g., more frequently harbored resistance genes than other taxa). We performed metagenomic functional profiling and metagenomic assembled genome analyses whose results indicate that the development of gut resistome was driven by changes in microbial carbohydrate metabolism, with an increasing need for carbohydrate-active enzymes from and a decreasing need for during infancy. Importantly, we observed increased acquired resistance genes over time, which was related to increased horizontal gene transfer in the developing infant gut microbiome. In summary, infant age was negatively correlated with antimicrobial resistance gene levels, reflecting a composition shift in the gut microbiome, likely driven by the changing need for microbial carbohydrate metabolism during early life.
PubMed: 38882494
DOI: 10.1002/imt2.169 -
Heliyon Jun 2024() is the causative agent of Tuberculosis, one of the deadliest infectious diseases. According to the WHO Report 2023, in 2022, approximately 10.6 million people got... (Review)
Review
() is the causative agent of Tuberculosis, one of the deadliest infectious diseases. According to the WHO Report 2023, in 2022, approximately 10.6 million people got infected with TB, and 1.6 million died. It has multiple antibiotics for treatment, but the major drawback of anti-tuberculosis therapy (ATT) is, its prolonged treatment duration. The major contributors to the lengthy treatment period are mycobacterial persistence and drug tolerance. Persistent is phenotypically drug tolerant and metabolically slow down which makes it difficult to be eliminated during ATT. These persisting bacteria are a huge reservoir of impending disease, waiting to get reactivated upon the onset of an immune compromising state. Directly Observed Treatment Short-course, although effective against replicating bacteria; fails to eliminate the drug-tolerant persisters making TB still the second-highest killer globally. There are different mechanisms for the development of drug-tolerant mycobacterial populations being investigated. Recently, the role of biofilms in the survival and host-evasion mechanism of persisters has come to light. Therefore, it is crucial to understand the mechanism of adaptation, survival and attainment of drug tolerance by persisting -populations, in order to design better immune responses and therapeutics for the effective elimination of these bacteria by reducing the duration of treatment and also circumvent the generation of drug-resistance to achieve the goal of global eradication of TB. This review summarizes the drug-tolerance mechanism and biofilms' role in providing a niche to dormant- We also discuss methods of targeting biofilms to achieve sterile eradication of the mycobacteria and prevent its reactivation by achieving adequate immune responses.
PubMed: 38882302
DOI: 10.1016/j.heliyon.2024.e32003 -
Veterinary Parasitology, Regional... Jul 2024The presence of Trypanosoma cruzi vectors in urban areas has been frequent, with colonization of homes and associated with reservoir animals that increase risk to...
The presence of Trypanosoma cruzi vectors in urban areas has been frequent, with colonization of homes and associated with reservoir animals that increase risk to humans, with simultaneous circulation of vectors and T. cruzi. The study aimed to describe the circulation of triatomines and T. cruzi in the Metropolitan Region of São Paulo, as well as evaluate risk situations. For analysis purposes, the triatomine notification information from January 2016 to July 2023 was used. While for Didelphis sp. collection with the aid of traps, notification information used was from 2019 to 2023. Information about triatomines came from spontaneous demand by the population and notification services were carried out by state field teams following defined protocols. 202 notifications were received with the capture of 448 triatomines. The positivity for T. cruzi observed was 60.5%. Regarding Didelphis sp., 416 animals were collected, 5.3% of which were positive for T. cruzi. There was overlapping areas of presence of infected triatomines and Didelphis sp., whose Discrete Typing Unit (DTU) was T. cruzi I. This work indicates the presence of infected vectors in urban areas, and the presence of a wild cycle of T. cruzi in didelphiids, reaffirming the need for and importance of vector surveillance work, through actions that can prevent the transmission of Chagas disease.
Topics: Animals; Trypanosoma cruzi; Chagas Disease; Brazil; Insect Vectors; Risk Assessment; Didelphis; Triatominae; Cities; Humans
PubMed: 38880572
DOI: 10.1016/j.vprsr.2024.101059 -
Veterinary Parasitology, Regional... Jul 2024Giardiasis is a small intestinal disease caused by the zoonotic parasite, Giardia duodenalis. This study presents the molecular findings of G. duodenalis infection in...
Giardiasis is a small intestinal disease caused by the zoonotic parasite, Giardia duodenalis. This study presents the molecular findings of G. duodenalis infection in companion dogs, domestic livestock and wildlife in the Northern Jordan Basin, Israel. Identification of G. duodenalis was accomplished by nested PCR (nPCR) targeting the 18S rRNA gene. Samples were collected from water (five samples from four sources of which one was recycled water), as well as feces from wolves (Canis lupus) (n = 34), jackals (Canis aureus) (n = 24), wild boars (Sus scrofa) (n = 40), cattle (Bos taurus) (n = 40), dogs (Canis lupus familiaris) (n = 37) and nutria (Mayocastor coypus) (n = 100). All positive samples were sequenced and a phylogenetic tree was drawn using the Bayesian Inference (BI) algorithm. Differences in G. duodenalis prevalence between the different hosts were analyzed by Pearson's chi-square (p < 0.05). Of the total 275 fecal samples, 36 were positive for G. duodenalis (13%). Frequency rates among different animal species was highest in wolves (32.3%), whilst rates in wild boars (22.5%), dogs (16.2%), cattle (12.5%) and jackals (4.2%), were observed to be significantly lower (p < 0.001). Three out of 5 recycled water (RW) samples were G. duodenalis positive. Three clusters with high posterior probabilities (PP) were found in the BI: Cluster 1: samples from wolves, wild boars, water and cattle together with database sequences of assemblages A, B and F, Cluster 2: samples from dogs, nutria and a jackal with sequences from assemblage D and Cluster 3: samples from cattle, wild boars, wolves and dogs with sequences from assemblage C and D. We suggest that wolves serve as reservoirs of G. duodenalis in this region. The finding of Giardia in RW suggests that this vehicle may further contaminate crops intended for human consumption as this water source is used for agricultural irrigation.
Topics: Animals; Dogs; Giardiasis; Giardia lamblia; Prevalence; Feces; Dog Diseases; Phylogeny; Israel; Animals, Wild; Livestock; RNA, Ribosomal, 18S; Cattle; Polymerase Chain Reaction; Pets
PubMed: 38880565
DOI: 10.1016/j.vprsr.2024.101042 -
Parasites & Vectors Jun 2024Powassan virus, a North American tick-borne flavivirus, can cause severe neuroinvasive disease in humans. While Ixodes scapularis are the primary vectors of Powassan...
BACKGROUND
Powassan virus, a North American tick-borne flavivirus, can cause severe neuroinvasive disease in humans. While Ixodes scapularis are the primary vectors of Powassan virus lineage II (POWV II), also known as deer tick virus, recent laboratory vector competence studies showed that other genera of ticks can horizontally and vertically transmit POWV II. One such tick is the Haemaphysalis longicornis, an invasive species from East Asia that recently established populations in the eastern USA and already shares overlapping geographic range with native vector species such as I. scapularis. Reports of invasive H. longicornis feeding concurrently with native I. scapularis on multiple sampled hosts highlight the potential for interspecies co-feeding transmission of POWV II. Given the absence of a clearly defined vertebrate reservoir host for POWV II, it is possible that this virus is sustained in transmission foci via nonviremic transmission between ticks co-feeding on the same vertebrate host. The objective of this study was to evaluate whether uninfected H. longicornis co-feeding in close proximity to POWV II-infected I. scapularis can acquire POWV independent of host viremia.
METHODS
Using an in vivo tick transmission model, I. scapularis females infected with POWV II ("donors") were co-fed on mice with uninfected H. longicornis larvae and nymphs ("recipients"). The donor and recipient ticks were infested on mice in various sequences, and mouse infection status was monitored by temporal screening of blood for POWV II RNA via quantitative reverse transcription polymerase chain reaction (q-RT-PCR).
RESULTS
The prevalence of POWV II RNA was highest in recipient H. longicornis that fed on viremic mice. However, nonviremic mice were also able to support co-feeding transmission of POWV, as demonstrated by the detection of viral RNA in multiple H. longicornis dispersed across different mice. Detection of viral RNA at the skin site of tick feeding but not at distal skin sites indicates that a localized skin infection facilitates transmission of POWV between donor and recipient ticks co-feeding in close proximity.
CONCLUSIONS
This is the first report examining transmission of POWV between co-feeding ticks. Against the backdrop of multiple unknowns related to POWV ecology, findings from this study provide insight on possible mechanisms by which POWV could be maintained in nature.
Topics: Animals; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Ixodes; Mice; Ixodidae; Female; Feeding Behavior; Introduced Species; Haemaphysalis longicornis; East Asian People
PubMed: 38879603
DOI: 10.1186/s13071-024-06335-0