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1.
Foods ; 13(9)2024 May 03.
Article in English | MEDLINE | ID: mdl-38731781

ABSTRACT

This study focused on the osmotic dehydration (OD) of ready-to-eat spinach leaves combined with the pulsed electric field (PEF) pre-treatment. Untreated and PEF-treated (0.6 kV/cm, 0-200 pulses) spinach leaves were osmotically dehydrated at room temperature for up to 120 min. The application of PEF (0.6 kV/20 pulses) prior to OD (60% glycerol, 25 °C, 60 min) lowered water activity (aw = 0.891) while achieving satisfactory product acceptability (total sensory hedonic scoring of 8). During the storage of the product (at 4, 8, 12, and 20 °C for up to 30 d), a significant reduction in total microbial count evolution was observed (9.7 logCFU/g for the untreated samples vs. 5.1 logCFU/g for the PEF-OD-treated samples after 13 d of storage at 4 °C). The selection of these PEF and OD treatment conditions enabled the extension of the product shelf life by up to 33 d under chilled storage. Osmotically treated spinach could find application in ready-to-eat salad products with an extended shelf life, which is currently not possible due to the high perishability of the specific plant tissue.

2.
Trends Parasitol ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38760256

ABSTRACT

Malaria remains a persistent global public health challenge because of the limitations of current prevention tools. The use of transgenic mosquitoes incapable of transmitting malaria, in conjunction with existing methods, holds promise for achieving elimination of malaria and preventing its reintroduction. In this context, population modification involves the spread of engineered genetic elements through mosquito populations that render them incapable of malaria transmission. Significant progress has been made in this field over the past decade in revealing promising targets, optimizing genetic tools, and facilitating the transition from the laboratory to successful field deployments, which are subject to regulatory scrutiny. This review summarizes recent advances and ongoing challenges in 'curing' Anopheles vectors of the malaria parasite.

3.
PLoS Pathog ; 20(4): e1012145, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38598552

ABSTRACT

Wolbachia, a maternally transmitted symbiotic bacterium of insects, can suppress a variety of human pathogens in mosquitoes, including malaria-causing Plasmodium in the Anopheles vector. However, the mechanistic basis of Wolbachia-mediated Plasmodium suppression in mosquitoes is not well understood. In this study, we compared the midgut and carcass transcriptomes of stably infected Anopheles stephensi with Wolbachia wAlbB to uninfected mosquitoes in order to discover Wolbachia infection-responsive immune genes that may play a role in Wolbachia-mediated anti-Plasmodium activity. We show that wAlbB infection upregulates 10 putative immune genes and downregulates 14 in midguts, while it upregulates 31 putative immune genes and downregulates 15 in carcasses at 24 h after blood-fed feeding, the time at which the Plasmodium ookinetes are traversing the midgut tissue. Only a few of these regulated immune genes were also significantly differentially expressed between Wolbachia-infected and non-infected midguts and carcasses of sugar-fed mosquitoes. Silencing of the Wolbachia infection-responsive immune genes TEP 4, TEP 15, lysozyme C2, CLIPB2, CLIPB4, PGRP-LD and two novel genes (a peritrophin-44-like gene and a macro domain-encoding gene) resulted in a significantly greater permissiveness to P. falciparum infection. These results indicate that Wolbachia infection modulates mosquito immunity and other processes that are likely to decrease Anopheles permissiveness to Plasmodium infection.


Subject(s)
Anopheles , Malaria, Falciparum , Plasmodium falciparum , Wolbachia , Animals , Anopheles/parasitology , Anopheles/microbiology , Anopheles/immunology , Wolbachia/immunology , Plasmodium falciparum/immunology , Malaria, Falciparum/immunology , Malaria, Falciparum/parasitology , Mosquito Vectors/parasitology , Mosquito Vectors/microbiology , Mosquito Vectors/immunology , Insect Proteins/genetics , Insect Proteins/metabolism , Insect Proteins/immunology , Transcriptome , Female
4.
J Fungi (Basel) ; 10(4)2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38667949

ABSTRACT

Amphotericin B (AmB) has long stood as a cornerstone in the treatment of invasive fungal infections (IFIs), especially among immunocompromised patients. However, the landscape of antifungal therapy is evolving. New antifungal agents, boasting novel mechanisms of action and better safety profiles, are entering the scene, presenting alternatives to AmB's traditional dominance. This shift, prompted by an increase in the incidence of IFIs, the growing demographic of immunocompromised individuals, and changing patterns of fungal resistance, underscores the continuous need for effective treatments. Despite these challenges, AmB's broad efficacy and low resistance rates maintain its essential status in antifungal therapy. Innovations in AmB formulations, such as lipid complexes and liposomal delivery systems, have significantly mitigated its notorious nephrotoxicity and infusion-related reactions, thereby enhancing its clinical utility. Moreover, AmB's efficacy in treating severe and rare fungal infections and its pivotal role as prophylaxis in high-risk settings highlight its value and ongoing relevance. This review examines AmB's standing amidst the ever-changing antifungal landscape, focusing on its enduring significance in current clinical practice and exploring its potential future therapeutic adaptations.

5.
Intensive Care Med ; 50(4): 502-515, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38512399

ABSTRACT

PURPOSE: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.


Subject(s)
Aspergillosis , Candidiasis, Invasive , Invasive Fungal Infections , Adult , Humans , Consensus , Invasive Fungal Infections/diagnosis , Aspergillosis/diagnosis , Candidiasis, Invasive/diagnosis , Intensive Care Units
6.
Viruses ; 16(3)2024 03 18.
Article in English | MEDLINE | ID: mdl-38543828

ABSTRACT

Primary Epstein-Barr virus (EBV) infection manifests with diverse clinical symptoms, occasionally resulting in severe complications. This scoping review investigates the rare occurrence of acute acalculous cholecystitis (AAC) in the context of primary EBV infection, with a focus on understanding its prevalence, clinical features, and underlying mechanisms. The study also explores EBV infection association with Gilbert syndrome, a condition that potentially exacerbates the clinical picture. Additionally, a case report of an 18-year-old female presenting with AAC and ascites secondary to EBV infection enhances the review. A comprehensive literature review was conducted, analyzing reported cases of AAC secondary to EBV infection. This involved examining patient demographics, clinical presentations, laboratory findings, and outcomes. The search yielded 44 cases, predominantly affecting young females. Common clinical features included fever, cervical lymphadenopathy, tonsillitis/pharyngitis, and splenomegaly. Laboratory findings highlighted significant hepatic involvement. The review also noted a potential link between AAC in EBV infection and Gilbert syndrome, particularly in cases with abnormal bilirubin levels. AAC is a rare but significant complication of primary EBV infection, primarily observed in young females, and may be associated with Gilbert syndrome. This comprehensive review underscores the need for heightened clinical awareness and timely diagnosis to manage this complication effectively.


Subject(s)
Acalculous Cholecystitis , Epstein-Barr Virus Infections , Gilbert Disease , Female , Humans , Adolescent , Acalculous Cholecystitis/complications , Acalculous Cholecystitis/diagnosis , Herpesvirus 4, Human , Gilbert Disease/complications , Ascites
7.
Foods ; 13(1)2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38201199

ABSTRACT

From a quality standpoint, it is desirable to preserve the characteristics of fresh-cut potatoes at their peak. However, due to the mechanical tissue damage during the cutting process, potatoes are susceptible to enzymatic browning. This study pertains to the selection of the appropriate osmotic dehydration (OD), high pressure (HP), and pulsed electric fields (PEF) processing conditions leading to effective quality retention of potato cuts. PEF (0.5 kV/cm, 200 pulses) or HP (400 MPa, 1 min) treatments prior to OD (35 °C, 120 min) were found to promote the retention of the overall quality (texture and color) of the samples. The incorporation of anti-browning agents (ascorbic acid and papain) into the osmotic solution improved the color retention, especially when combined with PEF or HP due to increased solid uptake (during OD) as indicated by DEI index (2.30, 1.93, and 2.10 for OD treated 120 min, non-pre-treated, HP pre-treated, and PEF pre-treated samples, respectively). PEF and HP combined with OD and anti-browning agent enrichment are sought to improve the quality and microbial stability of fresh-cut potatoes during refrigerator storage. Untreated fresh-cut potatoes were characterized by color degradation from the 2nd day of storage at 4 °C, and presented microbial growth (total viable counts: 6 log (CFU)/g) at day 6, whereas pre-treated potato samples retained their color and microbiologically stability after 6 days of cold storage (total viable counts, <4 log(CFU)/g).

8.
BMC Genomics ; 25(1): 42, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38191283

ABSTRACT

Gene-edited mosquitoes lacking a gamma-interferon-inducible lysosomal thiol reductase-like protein, namely (mosGILTnull) have lower Plasmodium infection, which is linked to impaired ovarian development and immune activation. The transcriptome of mosGILTnull Anopheles gambiae was therefore compared to wild type (WT) mosquitoes by RNA-sequencing to delineate mosGILT-dependent pathways. Compared to WT mosquitoes, mosGILTnull A. gambiae demonstrated altered expression of genes related to oogenesis, 20-hydroxyecdysone synthesis, as well as immune-related genes. Serendipitously, the zero population growth gene, zpg, an essential regulator of germ cell development was found to be one of the most downregulated genes in mosGILTnull mosquitoes. These results provide a crucial missing link between two previous studies on the role of zpg and mosGILT in ovarian development. This study further demonstrates that mosGILT has the potential to serve as a target for the biological control of mosquito vectors and to influence the Plasmodium life cycle within the vector.


Subject(s)
Anopheles , Animals , Anopheles/genetics , Cell Differentiation , Immunity, Innate/genetics , Mosquito Vectors/genetics , Germ Cells
9.
J Intensive Med ; 4(1): 81-93, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38263964

ABSTRACT

Background: The AbSeS-classification defines specific phenotypes of patients with intra-abdominal infection based on the (1) setting of infection onset (community-acquired, early onset, or late-onset hospital-acquired), (2) presence or absence of either localized or diffuse peritonitis, and (3) severity of disease expression (infection, sepsis, or septic shock). This classification system demonstrated reliable risk stratification in intensive care unit (ICU) patients with intra-abdominal infection. This study aimed to describe the epidemiology of ICU patients with pancreatic infection and assess the relationship between the components of the AbSeS-classification and mortality. Methods: This was a secondary analysis of an international observational study ("AbSeS") investigating ICU patients with intra-abdominal infection. Only patients with pancreatic infection were included in this analysis (n=165). Mortality was defined as ICU mortality within 28 days of observation for patients discharged earlier from the ICU. Relationships with mortality were assessed using logistic regression analysis and reported as odds ratio (OR) and 95% confidence interval (CI). Results: The overall mortality was 35.2% (n=58). The independent risk factors for mortality included older age (OR=1.03, 95% CI: 1.0 to 1.1 P=0.023), localized peritonitis (OR=4.4, 95% CI: 1.4 to 13.9 P=0.011), and persistent signs of inflammation at day 7 (OR=9.5, 95% CI: 3.8 to 23.9, P<0.001) or after the implementation of additional source control interventions within the first week (OR=4.0, 95% CI: 1.3 to 12.2, P=0.013). Gram-negative bacteria were most frequently isolated (n=58, 49.2%) without clinically relevant differences in microbial etiology between survivors and non-survivors. Conclusions: In pancreatic infection, a challenging source/damage control and ongoing pancreatic inflammation appear to be the strongest contributors to an unfavorable short-term outcome. In this limited series, essentials of the AbSeS-classification, such as the setting of infection onset, diffuse peritonitis, and severity of disease expression, were not associated with an increased mortality risk.ClinicalTrials.gov number: NCT03270345.

10.
Front Bioeng Biotechnol ; 11: 1261123, 2023.
Article in English | MEDLINE | ID: mdl-37965050

ABSTRACT

The field-testing and eventual adoption of genetically-engineered mosquitoes (GEMs) to control vector-borne pathogen transmission will require them meeting safety criteria specified by regulatory authorities in regions where the technology is being considered for use and other locales that might be impacted. Preliminary risk considerations by researchers and developers may be useful for planning the baseline data collection and field research used to address the anticipated safety concerns. Part of this process is to identify potential hazards (defined as the inherent ability of an entity to cause harm) and their harms, and then chart the pathways to harm and evaluate their probability as part of a risk assessment. The University of California Malaria Initiative (UCMI) participated in a series of workshops held to identify potential hazards specific to mosquito population modification strains carrying gene-drive systems coupled to anti-parasite effector genes and their use in a hypothetical island field trial. The hazards identified were placed within the broader context of previous efforts discussed in the scientific literature. Five risk areas were considered i) pathogens, infections and diseases, and the impacts of GEMs on human and animal health, ii) invasiveness and persistence of GEMs, and interactions of GEMs with target organisms, iii) interactions of GEMs with non-target organisms including horizontal gene transfer, iv) impacts of techniques used for the management of GEMs and v) evolutionary and stability considerations. A preliminary hazards list (PHL) was developed and is made available here. This PHL is useful for internal project risk evaluation and is available to regulators at prospective field sites. UCMI project scientists affirm that the subsequent processes associated with the comprehensive risk assessment for the application of this technology should be driven by the stakeholders at the proposed field site and areas that could be affected by this intervention strategy.

11.
Microorganisms ; 11(10)2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37894196

ABSTRACT

Antimicrobial resistance is a significant global health challenge, with Klebsiella pneumoniae being one of the most common antibiotic-resistant pathogens. This study provides an in-depth analysis of the prevalence and resistance patterns of antibiotic-resistant Klebsiella pneumoniae in the General Hospital of Corfu, Greece, between 2019 and 2022, with the aim of understanding the potential impact of the COVID-19 pandemic on the epidemiology of this bacterium. Utilizing a retrospective epidemiological approach, this study analyzed 212 isolates obtained from the hospital's Microbiology Department. These isolates were subjected to genotypic and phenotypic identification, with resistance genes (bla-KPC, bla-NDM, bla-VIM, bla-OXA-48, and mcr-1) and antibiotic resistance patterns as the primary focus. The results revealed a significant shift in resistance gene prevalence, with a notable increase in bla-KPC from 16.67% in 2021 to 58.46% in 2022, and a decrease in bla-NDM from 81.48% in 2021 to 38.46% in 2022. In terms of antibiotic resistance patterns, there was a consistent increase in resistance to amikacin and a significant decrease in resistance to ceftazidime/avibactam. These findings underscore the dynamic nature of carbapenem-resistant Klebsiella pneumoniae (CRKP) resistance and highlight the need for ongoing surveillance and adaptive therapeutic strategies in the face of evolving resistance patterns.

12.
Crit Care Resusc ; 25(1): 1-5, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37876989

ABSTRACT

Objective: To describe whether contemporary dosing of antifungal drugs achieves therapeutic exposures in critically ill patients that are associated with optimal outcomes. Adequate antifungal therapy is a key determinant of survival of critically ill patients with fungal infections. Critical illness can alter an antifungal agents' pharmacokinetics, increasing the risk of inappropriate antifungal exposure that may lead to treatment failure and/or toxicity. Design setting and participants: This international, multicentre, observational pharmacokinetic study will comprise adult critically ill patients prescribed antifungal agents including fluconazole, voriconazole, posaconazole, isavuconazole, caspofungin, micafungin, anidulafungin, and amphotericin B for the treatment or prophylaxis of invasive fungal disease. A minimum of 12 patients are targeted for enrolment for each antifungal agent, across 12 countries and 30 intensive care units to perform descriptive pharmacokinetics. Pharmacokinetic sampling will occur during two dosing intervals (occasions): firstly, between days 1 and 3, and secondly, between days 4 and 7 of the antifungal course, collecting three samples per occasion. Patients' demographic and clinical data will be collected. Main outcome measures: The primary endpoint of the study is attainment of pharmacokinetic/pharmacodynamic target exposures that are associated with optimal efficacy. Thirty-day mortality will also be measured. Results and conclusions: This study will describe whether contemporary antifungal drug dosing achieves drug exposures associated with optimal outcomes. Data will also be used for the development of antifungal dosing algorithms for critically ill patients. Optimised drug dosing should be considered a priority for improving clinical outcomes for critically ill patients with fungal infections.

13.
Microorganisms ; 11(9)2023 Aug 31.
Article in English | MEDLINE | ID: mdl-37764058

ABSTRACT

Antimicrobial resistance (AMR) poses a significant global health challenge, exacerbated by the COVID-19 pandemic. Antimicrobial stewardship programs (ASPs) are crucial in managing this crisis, with diagnostic stewardship (DS) emerging as a key component. DS refers to the appropriate use of diagnostic tests to optimize patient outcomes, improve antimicrobial use, and combat multi-drug-resistant (MDR) organisms. Despite its potential, understanding and application of DS remain ambiguous in multiple respects, which, however, do not directly implicate the implementation of such initiatives. DS is particularly important for resident physicians who are often at the forefront of patient care and can significantly influence future AMR strategies. This review provides a comprehensive overview of DS, discussing its importance, potential challenges, and future directions. It emphasizes the need for resident physicians to understand DS principles and integrate them into their clinical practice from the beginning of their careers. The review also highlights the role of various stakeholders in implementing DS and the importance of continuous education and training. Ultimately, DS is not just a clinical tool but a philosophy of care, essential for a more responsive, humane, and effective healthcare system.

14.
Nat Commun ; 14(1): 5773, 2023 09 18.
Article in English | MEDLINE | ID: mdl-37723154

ABSTRACT

Ae. aegypti mosquitoes transmit some of the most important human viral diseases that are responsible for a significant public health burden worldwide. The small interfering RNA (siRNA) pathway is considered the major antiviral defense system in insects. Here we show that siRNA pathway disruption by CRISPR/Cas9-based Ago2 knockout impaired the mosquitoes' ability to degrade arbovirus RNA leading to hyper-infection accompanied by cell lysis and tissue damage. Ago2 disruption impaired DNA repair mechanisms and the autophagy pathway by altering histone abundance. This compromised DNA repair and removal of damaged cellular organelles and dysfunctional aggregates promoted mosquito death. We also report that hyper-infection of Ago2 knockout mosquitoes stimulated a broad-spectrum antiviral immunity, including apoptosis, which may counteract infection. Taken together, our studies reveal novel roles for Ago2 in protecting mosquitoes from arbovirus infection and associated death.


Subject(s)
Aedes , Arbovirus Infections , Craniocerebral Trauma , Humans , Animals , Aedes/genetics , RNA, Small Interfering/genetics , Antiviral Agents , Apoptosis/genetics
15.
Antibiotics (Basel) ; 12(8)2023 Jul 30.
Article in English | MEDLINE | ID: mdl-37627675

ABSTRACT

Patients referred to intensive care units (ICU) commonly contract infections caused by multidrug-resistant (MDR) bacteria, which are typically linked to complications and high mortality. There are numerous independent factors that are associated with the transmission of these pathogens in the ICU. Preventive multilevel measures that target these factors are of great importance in order to break the chain of transmission. In this review, we aim to provide essential guidance for the development of robust prevention strategies, ultimately ensuring the safety and well-being of patients and healthcare workers in the ICU. We discuss the role of ICU personnel in cross-contamination, existing preventative measures, novel technologies, and strategies employed, along with antimicrobial surveillance and stewardship (AMSS) programs, to construct effective and thoroughly described policy recommendations. By adopting a multifaceted approach that combines targeted interventions with broader preventive strategies, healthcare facilities can create a more coherent line of defense against the spread of MDR pathogens. These recommendations are evidence-based, practical, and aligned with the needs and realities of the ICU setting. In conclusion, this comprehensive review offers a blueprint for mitigating the risk of MDR bacterial transmission in the ICU, advocating for an evidence-based, multifaceted approach.

16.
bioRxiv ; 2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37577703

ABSTRACT

Gene-edited mosquitoes lacking a g amma-interferon-inducible lysosomal thiol reductase-like protein, namely ( mosGILT null ) have lower Plasmodium infection, which is linked to impaired ovarian development and immune activation. The transcriptome of mosGILT null A. gambiae was therefore compared to wild type (WT) by RNA-sequencing to delineate mosGILT-dependent pathways. Compared to WT mosquitoes, mosGILT null A. gambiae demonstrated altered expression of genes related to oogenesis, 20-hydroxyecdysone synthesis, as well as immune-related genes. Serendipitously, the zero population growth gene, zpg , an essential regulator of germ cell development was found to be one of the most downregulated genes in mosGILT null mosquitoes. These results provide the crucial missing link between two previous studies on the role of zpg and mosGILT in ovarian development. This study further demonstrates that mosGILT has the potential to serve as a target for the biological control of mosquito vectors and to influence the Plasmodium life cycle within the vector.

17.
Proc Natl Acad Sci U S A ; 120(29): e2221118120, 2023 07 18.
Article in English | MEDLINE | ID: mdl-37428915

ABSTRACT

Proposed genetic approaches for reducing human malaria include population modification, which introduces genes into vector mosquitoes to reduce or prevent parasite transmission. We demonstrate the potential of Cas9/guide RNA (gRNA)-based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations. Two strains have an autonomous gene-drive system coupled to dual anti-Plasmodium falciparum effector genes comprising single-chain variable fragment monoclonal antibodies targeting parasite ookinetes and sporozoites in the African malaria mosquitoes Anopheles gambiae (AgTP13) and Anopheles coluzzii (AcTP13). The gene-drive systems achieved full introduction within 3 to 6 mo after release in small cage trials. Life-table analyses revealed no fitness loads affecting AcTP13 gene-drive dynamics but AgTP13 males were less competitive than wild types. The effector molecules reduced significantly both parasite prevalence and infection intensities. These data supported transmission modeling of conceptual field releases in an island setting that shows meaningful epidemiological impacts at different sporozoite threshold levels (2.5 to 10 k) for human infection by reducing malaria incidence in optimal simulations by 50 to 90% within as few as 1 to 2 mo after a series of releases, and by ≥90% within 3 mo. Modeling outcomes for low sporozoite thresholds are sensitive to gene-drive system fitness loads, gametocytemia infection intensities during parasite challenges, and the formation of potentially drive-resistant genome target sites, extending the predicted times to achieve reduced incidence. TP13-based strains could be effective for malaria control strategies following validation of sporozoite transmission threshold numbers and testing field-derived parasite strains. These or similar strains are viable candidates for future field trials in a malaria-endemic region.


Subject(s)
Anopheles , Malaria, Falciparum , Malaria , Animals , Male , Humans , Anopheles/genetics , Anopheles/parasitology , Mosquito Vectors/genetics , Malaria/prevention & control , Plasmodium falciparum/genetics , Sporozoites , Malaria, Falciparum/parasitology
18.
PLoS Pathog ; 19(6): e1011440, 2023 06.
Article in English | MEDLINE | ID: mdl-37319296

ABSTRACT

Long non-coding RNAs (lncRNAs) play critical regulatory roles in various cellular and metabolic processes in mosquitoes and all other organisms studied thus far. In particular, their involvement in essential processes such as reproduction makes them potential targets for the development of novel pest control approaches. However, their function in mosquito biology remains largely unexplored. To elucidate the role of lncRNAs in mosquitoes' reproduction and vector competence for arboviruses, we have implemented a computational and experimental pipeline to mine, screen, and characterize lncRNAs related to these two biological processes. Through analysis of publicly available Zika virus (ZIKV) infection-regulated Aedes aegypti transcriptomes, at least six lncRNAs were identified as being significantly upregulated in response to infection in various mosquito tissues. The roles of these ZIKV-regulated lncRNAs (designated Zinc1, Zinc2, Zinc3, Zinc9, Zinc10 and Zinc22), were further investigated by dsRNA-mediated silencing studies. Our results show that silencing of Zinc1, Zinc2, and Zinc22 renders mosquitoes significantly less permissive to ZIKV infection, while silencing of Zinc22 also reduces fecundity, indicating a potential role for Zinc22 in trade-offs between vector competence and reproduction. We also found that silencing of Zinc9 significantly increases fecundity but has no effect on ZIKV infection, suggesting that Zinc9 may be a negative regulator of oviposition. Our work demonstrates that some lncRNAs play host factor roles by facilitating viral infection in mosquitoes. We also show that lncRNAs can influence both mosquito reproduction and permissiveness to virus infection, two biological systems with important roles in mosquito vectorial capacity.


Subject(s)
Aedes , RNA, Long Noncoding , Zika Virus Infection , Zika Virus , Animals , Female , Zika Virus/physiology , Aedes/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Mosquito Vectors/genetics , Reproduction
19.
Viruses ; 15(5)2023 05 13.
Article in English | MEDLINE | ID: mdl-37243251

ABSTRACT

Cytomegalovirus (CMV) reactivation has been linked to adverse clinical outcomes in critically ill patients, with emerging evidence suggesting a potential connection with severe COVID-19. Mechanisms driving this association may include primary lung injury, amplification of systemic inflammation, and secondary immunosuppression. Diagnostic challenges in detecting and assessing CMV reactivation necessitate a comprehensive approach to improve accuracy and inform treatment decisions. Currently, there is limited evidence on the efficacy and safety of CMV pharmacotherapy in critically ill COVID-19 patients. Although insights from non-COVID-19 critical illness studies suggest a potential role for antiviral treatment or prophylaxis, the risks and benefits must be carefully balanced in this vulnerable patient population. Understanding the pathophysiological role of CMV in the context of COVID-19 and exploring the advantages of antiviral treatment are crucial for optimizing care in critically ill patients. This review provides a comprehensive synthesis of available evidence, emphasizing the need for additional investigation to establish the role of CMV treatment or prophylaxis in the management of severe COVID-19 and to develop a framework for future research on this topic.


Subject(s)
COVID-19 , Cytomegalovirus Infections , Humans , Antiviral Agents/therapeutic use , Cytomegalovirus Infections/prevention & control , Cytomegalovirus/physiology , Critical Illness , Intensive Care Units
20.
mBio ; 14(2): e0048023, 2023 04 25.
Article in English | MEDLINE | ID: mdl-37017525

ABSTRACT

Developing effective tools to control mosquito populations is essential for reducing the incidence of diseases like malaria and dengue. Biopesticides of microbial origin are a rich, underexplored source of mosquitocidal compounds. We previously developed a biopesticide from the bacterium Chromobacterium sp. Panama that rapidly kills vector mosquito larvae, including Aedes aegypti and Anopheles gambiae. Here, we demonstrate that two independent Ae. aegypti colonies exposed to a sublethal dose of that biopesticide over consecutive generations persistently exhibited high mortality and developmental delays, indicating that resistance did not develop during the study period. Critically, the descendants of biopesticide-exposed mosquitoes experienced decreased longevity and did not display increased susceptibility to dengue virus or decreased susceptibility to common chemical insecticides. Through RNA sequencing, we observed no link between biopesticide exposure and the increased activity of xenobiotic metabolism and detoxification genes typically associated with insecticide resistance. These findings indicate that the Chromobacterium biopesticide is an exciting, emerging mosquito control tool. IMPORTANCE Vector control is an essential part of mitigating diseases caused by pathogens that mosquitoes spread. Modern vector control is highly reliant on using synthetic insecticides to eliminate mosquito populations before they can cause disease. However, many of these populations have become resistant to commonly used insecticides. There is a strong need to explore alternative vector control strategies that aim to mitigate disease burden. Biopesticides, insecticides of biological origin, can have unique mosquitocidal activities, meaning they can effectively kill mosquitoes that are already resistant to other insecticides. We previously developed a highly effective mosquito biopesticide from the bacterium Chromobacterium sp. Csp_P. Here, we investigate whether exposure to a sublethal dose of this Csp_P biopesticide over 9 to 10 generations causes resistance to arise in Aedes aegypti mosquitoes. We find no evidence of resistance at the physiological or molecular levels, confirming that the Csp_P biopesticide is a highly promising new tool for controlling mosquito populations.


Subject(s)
Aedes , Insecticides , Animals , Insecticides/pharmacology , Biological Control Agents/pharmacology , Aedes/genetics , Chromobacterium/genetics , Mosquito Vectors/genetics , Larva
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