The Impact of Triclosan on the Spread of Antibiotic Resistance in the Environment

Triclosan (TCS) is a commonly used antimicrobial agent that enters wastewater treatment plants (WWTPs) and the environment. An estimated 1.1 × 105 to 4.2 × 105 kg of TCS are discharged from these WWTPs per year in the United States. The abundance of TCS along with its antimicrobial properties have given rise to concern regarding its impact on antibiotic resistance in the environment. The objective of this review is to assess the state of knowledge regarding the impact of TCS on multidrug resistance in environmental settings, including engineered environments such as anaerobic digesters. Pure culture studies are reviewed in this paper to gain insight into the substantially smaller body of research surrounding the impacts of TCS on environmental microbial communities. Pure culture studies, mainly on pathogenic strains of bacteria, demonstrate that TCS is often associated with multidrug resistance. Research is lacking to quantify the current impacts of TCS discharge to the environment, but it is known that resistance to TCS and multidrug resistance can increase in environmental microbial communities exposed to TCS. Research plans are proposed to quantitatively define the conditions under which TCS selects for multidrug resistance in the environment

Risk of acquired drug resistance during short-course directly observed treatment of tuberculosis in an area with high levels of drug resistance.

BACKGROUND: Data on the performance of standardized short-course directly observed treatment (DOTS) of tuberculosis (TB) in areas with high levels of drug resistance and on the potential impact of DOTS on amplification of resistance are limited. Therefore, we analyzed treatment results from a cross-sectional sample of patients with TB enrolled in a DOTS program in an area with high levels of drug resistance in Uzbekistan and Turkmenistan in Central Asia. METHODS: Sputum samples for testing for susceptibility to 5 first-line drugs and for molecular typing were obtained from patients starting treatment in 8 districts. Patients with sputum smear results positive for TB at the end of the intensive phase of treatment and/or at 2 months into the continuation phase were tested again. RESULTS. Among 382 patients with diagnoses of TB, 62 did not respond well to treatment and were found to be infected with an identical Mycobacterium tuberculosis strain when tested again; 19 of these patients had strains that developed new or additional drug resistance. Amplification occurred in only 1.2% of patients with initially susceptible or monoresistant TB strains, but it occurred in 17% of those with polyresistant strains (but not multidrug-resistant strains, defined as strains with resistance to at least isoniazid and rifampicin) and in 7% of those with multidrug-resistant strains at diagnosis. Overall, 3.5% of the patients not initially infected with multidrug-resistant TB strains developed such strains during treatment. Amplification of resistance, however, was found only in polyresistant Beijing genotype strains. CONCLUSIONS: High levels of amplification of drug resistance demonstrated under well-established DOTS program conditions reinforce the need for implementation of DOTS-Plus for multidrug-resistant TB in areas with high levels of drug resistance. The strong association of Beijing genotype and amplification in situations of preexisting resistance is striking and may underlie the strong association between this genotype and drug resistance

Mechanisms of cross resistance between cisplatin and bleomycin in saccharomyces cerevisiae

Tumor cells can simultaneously acquire resistance against a diverse group of drugs. This phenomenon is called pleotropic resistance or multidrug resistance. This mechanism could explain the tumor resistance observed in chemotherapy treatments with multiple agents. The aim of this work is to study possible mechanisms of cross resistance between Cisplatin and Bleomycin in Saccharomyces cerevisiae.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Genomic introgression mapping of field-derived multiple-anthelmintic resistance in Teladorsagia circumcincta

Preventive chemotherapy has long been practiced against nematode parasites of livestock, leading to widespread drug resistance, and is increasingly being adopted for eradication of human parasitic nematodes even though it is similarly likely to lead to drug resistance. Given that the genetic architecture of resistance is poorly understood for any nematode, we have analyzed multidrug resistant Teladorsagia circumcincta, a major parasite of sheep, as a model for analysis of resistance selection. We introgressed a field-derived multiresistant genotype into a partially inbred susceptible genetic background (through repeated backcrossing and drug selection) and performed genome-wide scans in the backcross progeny and drug-selected F2 populations to identify the major genes responsible for the multidrug resistance. We identified variation linking candidate resistance genes to each drug class. Putative mechanisms included target site polymorphism, changes in likely regulatory regions and copy number variation in efflux transporters. This work elucidates the genetic architecture of multiple anthelmintic resistance in a parasitic nematode for the first time and establishes a framework for future studies of anthelmintic resistance in nematode parasites of humans

Pemodelan Epidemiologi Kejadian Multidrug Resistance Bakteri Escherichia coli pada Peternakan Ayam Komersial di Kabupaten Blitar

Sifat resistensi bakteri Escherichia coli terhadap antibiotik mengakibatkan terbatasnya pilihan pengobatan. Perkembangan lebih lanjut dari resistensi bakteri dapat menyebabkan munculnya multidrug resistance pada bakteri, sehingga meningkatkan morbiditas dan mortalitas penyakit. Interaksi penyebaran kejadian multidrug resistance pada Escherichia coli yang terjadi pada populasi sangat kompleks, sehingga sulit memahami dinamika penyebaran berskala besar.  Pendekatan pemodelan menjadi sangat penting untuk pengambilan keputusan tentang program pengendalian penyakit infeksi. Penelitian ini merupakan penelitian epidemiologi deskriptif analitik dengan desain cross-sectional study. Metode analisis menggunakan analisis regresi logistic untuk mendapatkan pemodelan kejadian multidrug resistance bakteri Escherichia coli pada tingkat ternak, dan menggunakan regresi linier untuk mendapatkan pemodelan kejadian multidrug resistance bakteri Escherichia coli pada tingkat peternakan. Hasil dari penelitian ini menunjukkan Distribusi kasus kejadian multidrug resistance pada ayam komersial di Kabupaten Blitar menunjukkan prevalensi kejadian pada tingkat peternakan sebesar 95.9%. Pemodelan kejadian multidrug resistance bakteri Escherichia coli tingkat ternak menghasilkan model regresi logistik ganda Ln () = 0.21964 + 1.60374 RefTS + 1.44989 Broiler + 0.96022 PakRacik + 0.84182 ProgAb – 1.16667 SaniKan – 1.15046 Tritendap, dengan peluang kejadian sebesar 94 %. Pemodelan kejadian Multidrug resistance bakteri Escherichia coli tingkat peternakan menghasilkan model regresi linier, MDR (Y) = 0.57886 + 0.16105 JUMitra + 0.19342 ProgAb – 0.16178 Dukudrh. Model ini memiliki wilk saphiro mendekati 1 (W = 0,9573) sehingga model persamaan ini merupakan model yang baik untuk kejadian Multidrug resistance bakteri Escherichia coli tingkat peternakan

Genome Sequence of AvianEscherichia coliStrain IHIT25637, an Extraintestinal PathogenicE. coliStrain of ST131 Encoding Colistin Resistance Determinant MCR-1

Sequence type 131 (ST131) is one of the predominant Escherichia coli lineages among extraintestinal pathogenic E. coli (ExPEC) that causes a variety of diseases in humans and animals and frequently shows multidrug resistance. Here, we report the first genome sequence of an ST131-ExPEC strain from poultry carrying the plasmid-encoded colistin resistance gene mcr-1

Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro

OBJECTIVES: Conflicting data from studies on the potential role of multidrug resistance 1 gene polymorphisms in inflammatory bowel disease may result from the analysis of genetically and geographically distinct populations. Here, we investigated whether multidrug resistance 1 gene polymorphisms are associated with inflammatory bowel diseases in patients from Rio de Janeiro. METHODS: We analyzed 123 Crohn's disease patients and 83 ulcerative colitis patients to determine the presence of the multidrug resistance 1 gene polymorphisms C1236T, G2677T and C3435T. In particular, the genotype frequencies of Crohn's disease and ulcerative colitis patients were analyzed. Genotype-phenotype associations with major clinical characteristics were established, and estimated risks were calculated for the mutations. RESULTS: No significant difference was observed in the genotype frequencies of the multidrug resistance 1 G2677T/A and C3435T polymorphisms between Crohn's disease and ulcerative colitis patients. In contrast, the C1236T polymorphism was significantly more common in Crohn's disease than in ulcerative colitis (p = 0.047). A significant association was also found between the multidrug resistance 1 C3435T polymorphism and the stricturing form of Crohn's disease (OR: 4.13; p = 0.009), whereas no association was found with penetrating behavior (OR: 0.33; p = 0.094). In Crohn's disease, a positive association was also found between the C3435T polymorphism and corticosteroid resistance/refractoriness (OR: 4.14; p = 0.010). However, no significant association was found between multidrug resistance 1 gene polymorphisms and UC subphenotypic categories. CONCLUSION: The multidrug resistance 1 gene polymorphism C3435T is associated with the stricturing phenotype and an inappropriate response to therapy in Crohn's disease. This association with Crohn's disease may support additional pathogenic roles for the multidrug resistance 1 gene in regulating gut-microbiota interactions and in mediating fibrosis. Understanding the effects of several drugs associated with multidrug resistance 1 gene variants may aid in the selection of customized therapeutic regimens

Nanomedicines, a strategy to evade multidrug resistance

Multidrug resistance is a major problems associated with cancer chemotherapy. Efflux transports is one of the numerous mechanisms involved in multidrug resistance. P-glycoprotein is a transmembrane protein, responsible for drug efflux, which decreases drugs intracellular bioavailability, consequently decreasing their efficacy against cancer. Cancer growth and dissemination depends on the expression of transcriptional factors such as, Twist. Among other features, this protein is related with cells chemoresistance possible by regulation of multidrug resistance pathways including the P-glycoprotein expression. The herein study proposes to demonstrate if paclitaxel entrapped nanoparticles is an effective system in evading multidrug resistance mechanisms and if functionalization of a specific antibody against cancer stem cells receptors (anti-CD44v6) has the capability to target selectively these cells increasing nanoparticles efficacy. Therefore solid lipid nanoparticles were prepared and a breast cancer cell line (MDA-MB-436) was exposed to them in order to assess unloaded nanoparticles cytotoxic effects, increased pharmacologic efficacy of loaded nanoparticles relative to the free drug and their ability to evade multidrug resistance. The proposed solid lipid nanoparticles system proved to be capable of efficiently evading multidrug resistance mechanisms; however no improvement was added when these nanoparticles were functionalized with the antibody in the in vitro studies. However, the nanoparticles system is effective against multidrug resistance mechanisms