Lateral Antimicrobial Resistance Genetic Transfer is active in the open environment.
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ABSTRACT:
SUBMITTER: Chamosa LS
PROVIDER: S-EPMC5428826 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Publications
Lateral Antimicrobial Resistance Genetic Transfer is active in the open environment.
Chamosa Luciana S LS Álvarez Verónica E VE Nardelli Maximiliano M Quiroga María Paula MP Cassini Marcelo H MH Centrón Daniela D
Scientific reports 20170331 1
Historically, the environment has been viewed as a passive deposit of antimicrobial resistance mechanisms, where bacteria show biological cost for maintenance of these genes. Thus, in the absence of antimicrobial pressure, it is expected that they disappear from environmental bacterial communities. To test this scenario, we studied native IntI1 functionality of 11 class 1 integron-positive environmental strains of distant genera collected in cold and subtropical forests of Argentina. We found na ...[more]
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| S-EPMC9072757 | biostudies-literature
Project description:ObjectivesAntimicrobial resistance (AMR) is a significant threat to global public health. Many medical curricula have limited clinical cases and materials focused on AMR, yet enhanced AMR education and training are needed to support antimicrobial stewardship programmes. We used crowdsourcing methods to develop open-access, learner-centred AMR resources. Crowdsourcing is the process of having a large group, including experts and non-experts, solve a problem and then share solutions with the public.MethodsWe organised a global crowdsourcing contest soliciting AMR-related multiple-choice questions, infographics, and images. First, we convened a diverse steering committee group to finalise a call for entries. Second, we launched the contest and disseminated the call for entries using social media, blog posts, email, and an in-person event. Partner institutions included two digital healthcare platforms: Figure 1® and Ding Xiang Yuan. Both organizations serve as online communities for healthcare specialists and professionals to report and comment on clinical information. At the end of the call, solicited entries were screened for eligibility and judged on merit and relevance to AMR learning and education. Exceptional entries were recognised, awarded prizes, and further reviewed for sharing with the public via open-access platforms.ResultsWe received 59 entries from nine countries. These included 54 multiple-choice questions, four infographics, and one image. Eligible entries (n = 56) were reviewed and assigned a score on a 1-10 scale. Eight entries received mean scores greater than 6.0 and were selected as finalists. The eight finalist entries consisted of three infographics and five multiple-choice questions. They were disseminated through open-access publications and online medical communities. Although we launched a global call, we relied heavily on medical student groups and the entries received were not entirely globally representative.ConclusionsWe demonstrate that crowdsourcing challenge contests can be used to identify infectious disease teaching materials. Medical educators and curriculum developers can adapt this method to solicit additional teaching content for medical students.
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Project description:BACKGROUND:Nontuberculous mycobacteria (NTM) are ubiquitous in nature and recognized agents of opportunistic infection, which is often aggravated by their intrinsic resistance to antimicrobials, poorly defined therapeutic strategies and by the lack of new drugs. However, evaluation of their prevalence in anthropogenic environments and the associated antimicrobial resistance profiles have been neglected. In this work, we sought to determine minimal inhibitory concentrations of 25 antimicrobials against 5 NTM isolates recovered from a tertiary-care hospital surfaces. Antimicrobial susceptibilities of 5 other Corynebacterineae isolated from the same hospital were also determined for their potential clinical relevance. RESULTS:Our phylogenetic study with each of the NTM isolates confirm they belong to Mycobacterium obuense, Mycobacterium mucogenicum and Mycobacterium paragordonae species, the latter initially misidentified as strains of M. gordonae, a species frequently isolated from patients with NTM disease in Portugal. In contrast to other strains, the M. obuense and M. mucogenicum examined here were resistant to several of the CLSI-recommended drugs, suggestive of multidrug-resistant profiles. Surprisingly, M. obuense was susceptible to vancomycin. Their genomes were sequenced allowing detection of gene erm (erythromycin resistance methylase) in M. obuense, explaining its resistance to clarithromycin. Remarkably, and unlike other strains of the genus, the Corynebacterium isolates were highly resistant to penicillin, ciprofloxacin and linezolid. CONCLUSIONS:This study highlights the importance of implementing effective measures to screen, accurately identify and control viable NTM and closely related bacteria in hospital settings. Our report on the occurrence of rare NTM species with antibiotic susceptibility profiles that are distinct from those of the corresponding Type strains, along with unexpected resistance mechanisms detected seem to suggest that resistance may be more common than previously thought and also a potential threat to frail and otherwise vulnerable inpatients.
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Project description:BackgroundIt is prudent that novel classes of antibiotics be urgently developed to manage the WHO prioritized multi-drug resistant (MDR) pathogens posing an unprecedented medical crisis. Simultaneously, multiple essential proteins have to be targeted to prevent easy resistance development.MethodsAn integration of structure-based virtual screening and ligand-based virtual screening was employed to explore the antimicrobial properties of indole derivatives from a compound database.ResultsWhole-genome sequences of the target pathogens were aligned exploiting DNA alignment potential of MAUVE to identify putative common lead target proteins. S-adenosyl methionine (SAM) biosynthesizing MetK was taken as the lead target and various literature searches revealed that SAM is a critical metabolite. Furthermore, SAM utilizing CobA involved in the B12 biosynthesis pathway, Dam in the regulation of replication and protein expression, and TrmD in methylation of tRNA were also taken as drug targets. The ligand library of 715 indole derivatives chosen based on kinase inhibition potential of indoles was created from which 102 were pursued based on ADME/T scores. Among these, 5 potential inhibitors of MetK in N. gonorrhoeae were further expanded to molecular docking studies in MetK proteins of all nine pathogens among which 3 derivatives exhibited inhibition potential. These 3 upon docking in other SAM utilizing enzymes, CobA, Dam, and TrmD gave 2 potential compounds with multiple targets. Further, docking with human MetK homolog also showed probable inhibitory effects however SAM requirements can be replenished from external sources since SAM transporters are present in humans.ConclusionsWe believe these molecules 3-[(4-hydroxyphenyl)methyl]-6-(1H-indol-3-ylmethyl)piperazine-2,5-dione (ZINC04899565) and 1-[(3S)-3-[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyrrolidin-1-yl]ethanone (ZINC49171024) could be a starting point to help develop broad-spectrum antibiotics against infections caused by N. gonorrhoeae, A. baumannii, C. coli, K. pneumoniae, E. faecium, H. pylori, P. aeruginosa, S. aureus and S. typhi.
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