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References – Background of AMR

Ecology and evolution of antimicrobial resistance in bacterial communities

(Multidisciplinary Journal of Microbiological Ecology, 2020)

Abstract: Accumulating evidence suggests that the response of bacteria to antibiotics is significantly affected by the presence of other interacting microbes. These interactions are not typically accounted for when determining pathogen sensitivity to antibiotics. In this perspective, we argue that resistance and evolutionary responses to antibiotic treatments should not be considered only a trait of an individual bacteria species but also an emergent property of the microbial community in which pathogens are embedded. We outline how interspecies interactions can affect the responses of individual species and communities to antibiotic treatment, and how these responses could affect the strength of selection, potentially changing the trajectory of resistance evolution. Finally, we identify key areas of future research which will allow for a more complete understanding of antibiotic resistance in bacterial communities. We emphasise that acknowledging the ecological context, i.e. the interactions that occur between pathogens and within communities, could help the development of more efficient and effective antibiotic treatments.

Epistasis and the Evolution of Antimicrobial Resistance

(Frontiers in Microbiology, 2017)

Abstract: The fitness effects of a mutation can depend, sometimes dramatically, on genetic background; this phenomenon is often referred to as “epistasis.” Epistasis can have important practical consequences in the context of antimicrobial resistance (AMR). For example, genetic background plays an important role in determining the costs of resistance, and hence in whether resistance will persist in the absence of antibiotic pressure. Furthermore, interactions between resistance mutations can have important implications for the evolution of multi-drug resistance. I argue that there is a need to better characterize the extent and nature of epistasis for mutations and horizontally transferred elements conferring AMR, particularly in clinical contexts. Furthermore, I suggest that epistasis should be an important consideration in attempts to slow or limit the evolution of AMR.

Evolution of antimicrobial resistance among Enterobacteriaceae (focus on extended spectrum β-lactamases and carbapenemases)

(Expert Opinion on Pharmacotherapy, 2013)

Introduction: Bacteria within the family Enterobacteriaceae are important pathogens in nosocomial and community settings. Over the past two decades, antimicrobial resistance among Enterobacteriaceae dramatically escalated worldwide. The authors review the mechanisms of antimicrobial resistance among Enterobacteriaceae, epidemiology and global spread of resistance elements and discuss therapeutic options.
Areas covered: An exhaustive search for literature relating to Enterobacteriaceae was performed using PubMed, using the following key words: Enterobacteriaceae; Klebsiella pneumoniae; Escherichia coli; antimicrobial resistance; plasmids; global epidemiology; carbapenemases (CPEs); extended spectrum β-lactamases (ESBLs) and multidrug resistance (MDR).
Expert opinion: Enterobacteriaceae are inhabitants of intestinal flora and spread easily among humans (via hand carriage, contaminated food or water or environmental sources). Antimicrobial resistance may develop via plasmids, transposons or other mobile resistance elements. Mutations conferring resistance typically increase over time; the rate of increase is amplified by selection pressure from antibiotic use. Factors that enhance spread of antimicrobial resistance include: crowding; lack of hygiene; overuse and over-the-counter use of antibiotics; tourism; refugees and international travel. Clonal spread of resistant organisms among hospitals, geographic regions and continents has globally fueled the explosive rise in resistance. The emergence and widespread dissemination of MDR clones containing novel resistance elements (particularly ESBLs and CPEs) has greatly limited therapeutic options. In some cases, infections due to MDR Enterobacteriaceae are untreatable with existing antimicrobial agents. The authors discuss current and future therapeutic options for difficult-to-treat infections due to these organisms.

Natural Antibiotic Resistance and Contamination by Antibiotic Resistance Determinants: The Two Ages in the Evolution of Resistance to Antimicrobials

(Frontiers in Microbiology, 2012)

Abstract: The study of antibiotic resistance has been historically concentrated on the analysis of bacterial pathogens and on the consequences of acquiring resistance for human health. The development of antibiotic resistance is of course extremely relevant from the clinical point of view, because it can compromise the treatment of infectious diseases as well as other advanced therapeutic procedures as transplantation or anticancer therapy that involve immunosuppression and thus require robust anti-infective preventive therapies. Nevertheless, the studies on antibiotic resistance should not be confined to clinical-associated ecosystems

Origins and Evolution of Antibiotic Resistance

(Microbiology and Molecular Biology Reviews, 2010)

Abstract: Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man’s overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory.

The 2009 Garrod Lecture: The evolution of antimicrobial resistance: a Darwinian perspective

(Journal of Antimicrobial Chemotherapy, 2010)

Abstract: Microbes have evolved over 3.5 billion years and are arguably the most adaptable organisms on earth. Restricted genetically by their inability to reproduce sexually, bacteria have acquired several additional mechanisms by which to exchange genetic material horizontally. Such mechanisms have allowed bacteria to inhabit some of the most inhospitable environments on earth. It is thus hardly surprising that when faced with a barrage of inimical chemicals (antibiotics) they have responded with an equal and opposite force. This article compares and contrasts the evolution of antimicrobial resistance to β-lactam antibiotics over the last 70 years in two bacterial species, namely Staphylococcus aureus, a highly evolved human pathogen, and Pseudomonas aeruginosa, an opportunistic nosocomial pathogen.

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