Antimicrobial resistance: its emergence and transmission

2008 ◽  
Vol 9 (2) ◽  
pp. 115-126 ◽  
Author(s):  
Patrick Boerlin ◽  
Richard J. Reid-Smith

AbstractNew concepts have emerged in the past few years that help us to better understand the emergence and spread of antimicrobial resistance (AMR). These include, among others, the discovery of the mutator state and the concept of mutant selection window for resistances emerging primarily through mutations in existing genes. Our understanding of horizontal gene transfer has also evolved significantly in the past few years, and important new mechanisms of AMR transfer have been discovered, including, among others, integrative conjugative elements and ISCR(insertionsequences withcommonregions) elements. Simultaneously, large-scale studies have helped us to start comprehending the immense and yet untapped reservoir of both AMR genes and mobile genetic elements present in the environment. Finally, new PCR- and DNA sequencing-based techniques are being developed that will allow us to better understand the epidemiology of classical vectors of AMR genes, such as plasmids, and to monitor them in a more global and systematic way.

Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 890
Author(s):  
Eva Cunha ◽  
Rita Janela ◽  
Margarida Costa ◽  
Luís Tavares ◽  
Ana Salomé Veiga ◽  
...  

Periodontal disease (PD) is one of the most common diseases in dogs. Although previous studies have shown the potential of the antimicrobial peptide nisin for PD control, there is no information regarding its influence in the development of antimicrobial resistance or horizontal gene transfer (HGT). Nisin’s mutant prevention concentration (MPC) and selection window (MSW) were determined for a collection of canine oral enterococci. Isolates recovered after the determination of the MPC values were characterized for their antimicrobial profile and its nisin minimum inhibitory and bactericidal concentrations. The potential of vanA HGT between Enterococcus faecium CCGU36804 and nine clinical canine staphylococci and enterococci was evaluated. Nisin MPC values ranged from 400 to more than 600 μg/mL. In comparison with the original enterococci collection, the isolates recovered after the determination of the nisin MPC showed increased resistance towards amoxicillin/clavulanate (5%), vancomycin (5%), enrofloxacin (10%), gentamicin (10%) and imipenem (15%). The HGT of vanA gene was not observed. This work showed that nisin selective pressure may induce changes in the bacteria’s antimicrobial resistance profile but does not influence horizontal transfer of vanA gene. To our knowledge, this is the first report of nisin’s MPC and MSW determination regarding canine enterococci.


2017 ◽  
Author(s):  
Kathrin Trappe ◽  
Ben Wulf ◽  
Joerg Doellinger ◽  
Sven Halbedel ◽  
Thilo Muth ◽  
...  

Horizontal gene transfer (HGT) is a powerful mechanism that allows bacteria to directly transfer long stretches of genomic sequence from one individual to another. The transfer of antimicrobial resistance genes is a prominent example of HGT events in the context of multi-resistant bacteria which pose a high risk to human health. While several approaches for HGT detection exist on the genomic level, to the best of our knowledge, HGT events have not been investigated in a detailed mass spectrometry (MS)-based proteomic study. However, the mere presence of a gene does not necessarily correlate with its expression at the protein level. Consequently, to draw conclusions with respect to the expression of HGT-mediated genes, MS-based proteomics can be employed. We developed a first computational approach - called Hortense - for automated HGT detection directly from shotgun proteomics experiments. We extend the standard database search by a critical cross-validation to unravel potential HGT proteins. A proteogenomic extension gives information about the genomic origin and enables an integration with existing genome-based methods. We successfully validated our approach on simulated data, and further evaluated it on real data from a transgenic organism and a negative control from an organism not harboring a transferred gene. Our results indicate that our method facilitates MS-based analysis for proteomic evidence of HGT events. Especially as an orthogonal approach to genome-based HGT detection methods, our proposed workflow is a first step toward a systematic and large scale analysis of HGT events in, e.g., antimicrobial resistance context. Hortense is publicly available at https://gitlab.com/rki_bioinformatics/.


Author(s):  
Kathrin Trappe ◽  
Ben Wulf ◽  
Joerg Doellinger ◽  
Sven Halbedel ◽  
Thilo Muth ◽  
...  

Horizontal gene transfer (HGT) is a powerful mechanism that allows bacteria to directly transfer long stretches of genomic sequence from one individual to another. The transfer of antimicrobial resistance genes is a prominent example of HGT events in the context of multi-resistant bacteria which pose a high risk to human health. While several approaches for HGT detection exist on the genomic level, to the best of our knowledge, HGT events have not been investigated in a detailed mass spectrometry (MS)-based proteomic study. However, the mere presence of a gene does not necessarily correlate with its expression at the protein level. Consequently, to draw conclusions with respect to the expression of HGT-mediated genes, MS-based proteomics can be employed. We developed a first computational approach - called Hortense - for automated HGT detection directly from shotgun proteomics experiments. We extend the standard database search by a critical cross-validation to unravel potential HGT proteins. A proteogenomic extension gives information about the genomic origin and enables an integration with existing genome-based methods. We successfully validated our approach on simulated data, and further evaluated it on real data from a transgenic organism and a negative control from an organism not harboring a transferred gene. Our results indicate that our method facilitates MS-based analysis for proteomic evidence of HGT events. Especially as an orthogonal approach to genome-based HGT detection methods, our proposed workflow is a first step toward a systematic and large scale analysis of HGT events in, e.g., antimicrobial resistance context. Hortense is publicly available at https://gitlab.com/rki_bioinformatics/.


2020 ◽  
Author(s):  
Michael W J Hall ◽  
David Shorthouse ◽  
Philip H Jones ◽  
Benjamin A Hall

AbstractThe recent development of highly sensitive DNA sequencing techniques has detected large numbers of missense mutations of genes, including NOTCH1 and 2, in ageing normal tissues. Driver mutations persist and propagate in the tissue through a selective advantage over both wild-type cells and alternative mutations. This process of selection can be considered as a large scale, in vivo screen for mutations that increase clone fitness. It follows that the specific missense mutations that are observed in individual genes may offer us insights into the structure-function relationships. Here we show that the positively selected missense mutations in NOTCH1 and NOTCH2 in human oesophageal epithelium cause inactivation predominantly through protein misfolding. Once these mutations are excluded, we further find statistically significant evidence for selection at the ligand binding interface and calcium binding sites. In this, we observe stronger evidence of selection at the ligand interface on EGF12 over EGF11, suggesting that in this tissue EGF12 may play a more important role in ligand interaction. Finally, we show how a mutation hotspot in the NOTCH1 transmembrane helix arises through the intersection of both a high mutation rate and residue conservation. Together these insights offer a route to understanding the mechanism of protein function through in vivo mutant selection.


2021 ◽  
Vol 1 (1) ◽  
pp. 3-24
Author(s):  
Md. Jannat Hossain ◽  
Youssef Attia ◽  
Fatimah Muhammad Ballah ◽  
Md. Saiful Islam ◽  
Md. Abdus Sobur ◽  
...  

Antimicrobial resistance (AMR) in Salmonella in poultry poses a serious human health threat as it has zoonotic importance. Poultry is often linked with outbreaks of Salmonella-associated foodborne illness. Since antimicrobials are heavily used in poultry in Bangladesh, multidrug-resistant (MDR) Salmonella is quite frequently found there. MDR Salmonella is challenging to treat with antimicrobials and often causes a severe economic loss in the poultry sector. By horizontal gene transfer and/or evolutionary mutations, antimicrobials primarily exert selection pressure that contributes to antimicrobials resistance. In addition, resistance patterns can vary with variations in time and space. Without having prior knowledge of resistance patterns, no effective drugs could be prescribed. Therefore, it is crucial to have updated knowledge on the status of AMR in Salmonella in Bangladesh for effective treatment and management of the flocks against salmonellosis. There are several review articles on AMR in Salmonella in poultry in Bangladesh; they lack the whole scenario of the country and particularly do not have enough data on the poultry environment. Considering this scenario, in this review, we have focused on AMR in Salmonella in poultry in Bangladesh (2011–2021), with particular emphasis on data from the poultry and farm environments on a divisional zone basis.


2016 ◽  
Vol 7 ◽  
Author(s):  
Christian J. H. von Wintersdorff ◽  
John Penders ◽  
Julius M. van Niekerk ◽  
Nathan D. Mills ◽  
Snehali Majumder ◽  
...  

Genes ◽  
2019 ◽  
Vol 10 (8) ◽  
pp. 569 ◽  
Author(s):  
Phale ◽  
Shah ◽  
Malhotra

In the biosphere, the largest biological laboratory, increased anthropogenic activities have led microbes to evolve and adapt to the changes occurring in the environment. Compounds, specifically xenobiotics, released due to such activities persist in nature and undergo bio-magnification in the food web. Some of these compounds act as potent endocrine disrupters, mutagens or carcinogens, and therefore their removal from the environment is essential. Due to their persistence, microbial communities have evolved to metabolize them partially or completely. Diverse biochemical pathways have evolved or been assembled by exchange of genetic material (horizontal gene transfer) through various mobile genetic elements like conjugative and non-conjugative plasmids, transposons, phages and prophages, genomic islands and integrative conjugative elements. These elements provide an unlimited opportunity for genetic material to be exchanged across various genera, thus accelerating the evolution of a new xenobiotic degrading phenotype. In this article, we illustrate examples of the assembly of metabolic pathways involved in the degradation of naphthalene and its derivative, Carbaryl, which are speculated to have evolved or adapted through the above-mentioned processes.


2013 ◽  
Author(s):  
Kevin Dougherty ◽  
Brian A Smith ◽  
Autum F Moore ◽  
Shannon Maitland ◽  
Chris Fanger ◽  
...  

Horizontal gene transfer often leads to phenotypic changes within recipient organisms independent of any immediate evolutionary benefits. While secondary phenotypic effects of horizontal transfer (i.e. changes in growth rates) have been demonstrated and studied across a variety of systems using relatively small plasmid and phage, little is known about how size of the acquired region affects the magnitude or number of such costs. Here we describe an amazing breadth of phenotypic changes which occur after a large-scale horizontal transfer event (~1Mb megaplasmid) within Pseudomonas stutzeri including sensitization to various stresses as well as changes in bacterial behavior. These results highlight the power of horizontal transfer to shift pleiotropic relationships and cellular networks within bacterial genomes. They also provide an important context for how secondary effects of transfer can bias evolutionary trajectories and interactions between species. Lastly, these results and system provide a foundation to investigate evolutionary consequences in real time as newly acquired regions are ameliorated and integrated into new genomic contexts.


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