Welcome to the IUMS 2022 Interactive Program

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Drug-resistance in herpesviruses is virtually not observed in immunocompetent individuals but it is a well-recognized problem among different populations of immunocompromised patients. Therefore, in 2009 a Reference and Service Center, RegaVir [Research Group for Antiviral Resistance, (www.regavir.org)], for the diagnosis and typing of drug-resistant herpesviruses was established in Belgium, which was recognized in 2015 as National Reference Center.

Phenotyping (drug-susceptibility profile) and/or genotyping {PCR amplification of viral genes involved in drug-resistance [UL97 protein kinase and DNA polymerase (DNA pol) for cytomegalovirus (CMV); thymidine kinase and DNA pol for herpes simplex virus (HSV) and varicella-zoster virus (VZV), and U69 protein kinase and DNA pol for human herpesvirus 6 (HHV-6], followed by DNA sequencing} are used to diagnose drug-resistance among human herpesviruses according to the virus and the type of sample. Today, in the context of the RegaVir platform, we have analyzed >2,500 clinical samples recovered from patients who were refractory to antiviral therapy. Our data show: a) the usefulness of rapid genotyping and/or phenotyping for the adjustment of antiviral therapy, b) a considerable number of isolates bearing mutations linked to drug-resistance among the samples that proved positive for virus isolation and/or PCR amplification, c) the identification of unknown genetic polymorphisms and of novel mutations linked to drug-resistance, d) a higher risk for developing drug-resistance infections in the central nervous system, e) emergence of multiple drug-resistance due to the presence of a specific DNA pol mutation or conferred by infection with multiple viral strains, f) compartmentalization of herpesvirus populations, g) relative rapid evolution and heterogenicity of herpesviruses, h) advantage of next generation sequencing over capillary sequencing for detection of emergence of minor populations of drug-resistant viruses, i) an important number of simultaneous and concomitant infection with different herpesviruses among immunocompromised patients

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Among Enterococci, intrinsic and acquired resistance to antibiotics such as β-lactams and vancomycin critically limit treatment options for infection with these opportunistic pathogens. We have recently shown that Enterococus faecalis exists as both an extracellular pathogen and also replicates within a variety of mammalian cells, including macrophages, further complicates treatment of infections caused by this opportunistic pathogen. Antimicrobials that enhance the host immune response are emerging as alternative approaches, with the added advantage of overcoming bacterial resistance. Here, we investigate the antibiotic and immunological activity of an FDA-approved anticancer agent in vitro and in vivo against vancomycin resistant Enterococcus faecalis (VRE). In vitro, this drug is a potent antibiotic against Gram-positive bacteria through induction of reactive oxygen species and DNA damage. At sub-inhibitory concentrations, this drug synergises with vancomycin and lowers the vancomycin concentration required to kill VRE by over 140-fold. This synergy is specific to vancomycin-resistant, but not susceptible, strains because vancomycin renders the resistant strains more permeable to this drug and thus drug-mediated DNA damage. In a murine wound infection model, treatment with this drug effectively reduced VRE bacterial numbers by 120-fold and with further reductions when combined with vancomycin. Wounds treated with this drug had significantly more macrophages and pro-inflammatory cytokines compared to untreated wounds. In addition, this drug augmented intracellular bacterial killing by both murine and human macrophages by upregulating the expression of lysosomal hydrolases. These results show that this drug is a potent antibiotic against Gram-positive bacteria, sensitizes VRE to vancomycin, enhances macrophage recruitment and intracellular bactericidal activity, and represent a promising dual bacterium- and host-targeted therapeutic for overcoming vancomycin resistance.

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Bananas are very important global export commodities and staple food. One major problem in banana production is the black leaf streak disease (BLSD, also known as black Sigatoka) caused by Pseudocercospora fijiensis. Banana’s susceptibility to BLSD pushes disease management to excessive chemical use, largely relying on contact and systemic fungicides. Particularly, systemic fungicides are ubiquitous in plant disease control, targeting specific cell molecules and generating resistant mechanism in the species. We will discuss P. fijiensis loss of sensitivity towards most common systemic fungicide and the molecular mechanisms behind the resistant. We will also elaborate how the loss of sensitivity in systemic fungicide increases the use of contact fungicide with the consequent negative impact on the environment, human health and crop sustainability. The discussion will be based on the last findings on the pathogen´s field populations from various major banana production and wild zones in Colombia, Costa Rica, Dominican Republic, Ecuador, the Philippines, Guadalupe, Martinique and Cameroon. We hope these data significantly contributes to the understanding of the evolution and global distribution of the resistance mechanisms in P. fijiensis field populations and facilitates the search for alternative ways to control the disease. The overall reduced fungicide sensitivity calls for the deployment of a wider range of solutions for a sustainable control of this major banana disease.