Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens

Urogenital mycoplasmas (Mycoplasma genitalium, Mycoplasma hominis and Ureaplasma spp.) currently prevail in the etiology of infections of the urogenital tract and are characterized by a high level of genetic polymorphism responsible for the occurrence of their antibiotic resistance. The review presents the data of domestic and foreign researchers on the resistance mechanisms of mycoplasmas and ureaplasmas to antibiotics and considers the acquisition by mycoplasmas of antibiotic resistance determinants. New knowledge of resistance mechanisms is important theoretical basis for improving measures to limit and prevent the spread of antibiotic resistant bacteria.

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Ecology and Evolution as Targets: the Need for Novel Eco-Evo Drugs and Strategies To Fight Antibiotic Resistance

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00013-11 ◽

2011 ◽

Vol 55 (8) ◽

pp. 3649-3660 ◽

Cited By ~ 121

Author(s):

Fernando Baquero ◽

Teresa M. Coque ◽

Fernando de la Cruz

Keyword(s):

Antibiotic Resistance ◽

Global Dimension ◽

Regulatory Agencies ◽

Antibiotic Prescribing ◽

Individual Level ◽

Resistance Determinants ◽

Environmental Bacteria ◽

Potential Damage ◽

The Individual ◽

Microbial Systems

ABSTRACTIn recent years, the explosive spread of antibiotic resistance determinants among pathogenic, commensal, and environmental bacteria has reached a global dimension. Classical measures trying to contain or slow locally the progress of antibiotic resistance in patients on the basis of better antibiotic prescribing policies have clearly become insufficient at the global level. Urgent measures are needed to directly confront the processes influencing antibiotic resistance pollution in the microbiosphere. Recent interdisciplinary research indicates that new eco-evo drugs and strategies, which take ecology and evolution into account, have a promising role in resistance prevention, decontamination, and the eventual restoration of antibiotic susceptibility. This minireview summarizes what is known and what should be further investigated to find drugs and strategies aiming to counteract the “four P's,” penetration, promiscuity, plasticity, and persistence of rapidly spreading bacterial clones, mobile genetic elements, or resistance genes. The term “drug” is used in this eco-evo perspective as a tool to fight resistance that is able to prevent, cure, or decrease potential damage caused by antibiotic resistance, not necessarily only at the individual level (the patient) but also at the ecological and evolutionary levels. This view offers a wealth of research opportunities for science and technology and also represents a large adaptive challenge for regulatory agencies and public health officers. Eco-evo drugs and interventions constitute a new avenue for research that might influence not only antibiotic resistance but the maintenance of a healthy interaction between humans and microbial systems in a rapidly changing biosphere.

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Unravelling native plant resistomes – The Sphagnum microbiome harbours versatile and novel antimicrobial resistance genes

10.1101/695973 ◽

2019 ◽

Cited By ~ 1

Author(s):

Melanie-Maria Obermeier ◽

Julian Taffner ◽

Alessandro Bergna ◽

Anja Poehlein ◽

Tomislav Cernava ◽

...

Keyword(s):

Antibiotic Resistance ◽

Antimicrobial Resistance ◽

Resistance Genes ◽

Resistance Mechanisms ◽

Culture Collection ◽

Metagenomic Data ◽

Native Plant ◽

Resistance Determinants ◽

Target Spectrum ◽

Antimicrobial Resistance Genes

The expanding antibiotic resistance crisis calls for a more in depth understanding of the importance of antimicrobial resistance genes (ARGs) in pristine environments. We, therefore, studied the microbiota associated with Sphagnum forming the main vegetation in undomesticated, evolutionary old bog ecosystems. In our complementary analysis of a culture collection, metagenomic data and a fosmid library, we identified a low abundant but highly diverse pool of resistance determinants, which targets an unexpected broad range of antibiotics including natural and synthetic compounds. This derives both, from the extraordinarily high abundance of efflux pumps (80%), and the unexpectedly versatile set of ARGs underlying all major resistance mechanisms. The overall target spectrum of detected resistance determinants spans 21 antibiotic classes, whereby β-lactamases and vancomycin resistance appeared as the predominant resistances in all screenings. Multi-resistance was frequently observed among bacterial isolates, e.g. in Serratia, Pandorea, Paraburkhotderia and Rouxiella. In a search for novel ARGs we identified the new class A β-lactamase Mm3. The native Sphagnum resistome comprising a highly diversified and partially novel set of ARGs contributes to the bog ecosystem’s plasticity. Our results shed light onto the antibiotic resistance background of non-agricultural plants and highlight the ecological link between natural and clinically relevant resistomes.

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Novel Antibiotic Resistance Determinants from Agricultural Soil Exposed to Antibiotics Widely Used in Human Medicine and Animal Farming

Applied and Environmental Microbiology ◽

10.1128/aem.00989-17 ◽

2017 ◽

Vol 83 (16) ◽

Cited By ~ 32

Author(s):

Calvin Ho-Fung Lau ◽

Kalene van Engelen ◽

Stephen Gordon ◽

Justin Renaud ◽

Edward Topp

Keyword(s):

Antibiotic Resistance ◽

Agricultural Soil ◽

Resistance Mechanism ◽

Antibiotic Resistance Genes ◽

Resistance Mechanisms ◽

Human Medicine ◽

Natural Environments ◽

Functional Metagenomics ◽

Proteomics Analysis ◽

Resistance Determinants

ABSTRACT Antibiotic resistance has emerged globally as one of the biggest threats to human and animal health. Although the excessive use of antibiotics is recognized as accelerating the selection for resistance, there is a growing body of evidence suggesting that natural environments are “hot spots” for the development of both ancient and contemporary resistance mechanisms. Given that pharmaceuticals can be entrained onto agricultural land through anthropogenic activities, this could be a potential driver for the emergence and dissemination of resistance in soil bacteria. Using functional metagenomics, we interrogated the “resistome” of bacterial communities found in a collection of Canadian agricultural soil, some of which had been receiving antibiotics widely used in human medicine (macrolides) or food animal production (sulfamethazine, chlortetracycline, and tylosin) for up to 16 years. Of the 34 new antibiotic resistance genes (ARGs) recovered, the majority were predicted to encode (multi)drug efflux systems, while a few share little to no homology with established resistance determinants. We characterized several novel gene products, including putative enzymes that can confer high-level resistance against aminoglycosides, sulfonamides, and broad range of beta-lactams, with respect to their resistance mechanisms and clinical significance. By coupling high-resolution proteomics analysis with functional metagenomics, we discovered an unusual peptide, PPPAZI 4, encoded within an alternative open reading frame not predicted by bioinformatics tools. Expression of the proline-rich PPPAZI 4 can promote resistance against different macrolides but not other ribosome-targeting antibiotics, implicating a new macrolide-specific resistance mechanism that could be fundamentally linked to the evolutionary design of this peptide. IMPORTANCE Antibiotic resistance is a clinical phenomenon with an evolutionary link to the microbial pangenome. Genes and protogenes encoding specialized and potential resistance mechanisms are abundant in natural environments, but understanding of their identity and genomic context remains limited. Our discovery of several previously unknown antibiotic resistance genes from uncultured soil microorganisms indicates that soil is a significant reservoir of resistance determinants, which, once acquired and “repurposed” by pathogenic bacteria, can have serious impacts on therapeutic outcomes. This study provides valuable insights into the diversity and identity of resistance within the soil microbiome. The finding of a novel peptide-mediated resistance mechanism involving an unpredicted gene product also highlights the usefulness of integrating proteomics analysis into metagenomics-driven gene discovery.

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Molecular Epidemiology of Carbapenem-Resistant Acinetobacter baumannii From Khartoum State, Sudan

Frontiers in Microbiology ◽

10.3389/fmicb.2021.628736 ◽

2021 ◽

Vol 12 ◽

Author(s):

Leena Al-Hassan ◽

Hana Elbadawi ◽

Einas Osman ◽

Sara Ali ◽

Kamal Elhag ◽

...

Keyword(s):

Antibiotic Resistance ◽

Molecular Epidemiology ◽

Acinetobacter Baumannii ◽

Core Genome ◽

Treatment Options ◽

Resistance Mechanisms ◽

Multiple Antibiotic Resistance ◽

Resistance Determinants ◽

Carbapenem Resistant ◽

Allelic Differences

Carbapenem resistant Acinetobacter baumannii (CRAb) is an important global pathogen contributing to increased morbidity and mortality in hospitalized patients, due to limited alternative treatment options. Nine international clonal (IC) lineages have been identified in many countries worldwide, however, data still lacks from some parts of the world, particularly in Africa. We hereby present the molecular epidemiology of MDR A. baumannii from four hospitals in Khartoum, Sudan, collected from 2017 to 2018. Forty-two isolates were whole-genome sequenced, and subsequent molecular epidemiology was determined by core genome MLST (cgMLST), and their resistomes identified. All isolates had an array of diverse antibiotic resistance mechanisms conferring resistance to multiple classes of antibiotics. We found a predominance (88%) of IC2 (with the intrinsic OXA-66 and acquired OXA-23), and some with NDM-1. IC2 isolates were sub-divided into 4 STs separated by 5 to 431 allelic differences, and with evidence of seven transmission clusters. Isolates belonging to IC1, IC5, and IC9 were also identified. These data illustrate that MDR IC2 A. baumannii are widely distributed in Khartoum hospitals and are in possession of multiple antibiotic resistance determinants.

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Sampling the Antibiotic Resistome

Science ◽

10.1126/science.1120800 ◽

2006 ◽

Vol 311 (5759) ◽

pp. 374-377 ◽

Cited By ~ 872

Author(s):

Vanessa M. D'Costa ◽

Katherine M. McGrann ◽

Donald W. Hughes ◽

Gerard D. Wright

Keyword(s):

Antibiotic Resistance ◽

Microbial Community ◽

Drug Discovery ◽

Early Warning ◽

Early Warning System ◽

Warning System ◽

Resistance Mechanisms ◽

Community Study ◽

Synthetic Compounds ◽

Resistance Determinants

Microbial resistance to antibiotics currently spans all known classes of natural and synthetic compounds. It has not only hindered our treatment of infections but also dramatically reshaped drug discovery, yet its origins have not been systematically studied. Soil-dwelling bacteria produce and encounter a myriad of antibiotics, evolving corresponding sensing and evading strategies. They are a reservoir of resistance determinants that can be mobilized into the microbial community. Study of this reservoir could provide an early warning system for future clinically relevant antibiotic resistance mechanisms.

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Antibiotic resistance profile and occurrence of AmpC between Pseudomonas aeruginosa isolated from a domestic full-scale WWTP in southeast Brazil

Water Science & Technology ◽

10.2166/wst.2018.091 ◽

2018 ◽

Vol 2017 (1) ◽

pp. 108-114 ◽

Cited By ~ 5

Author(s):

Luiza Gerçossimo Oliveira ◽

Letícia Gonçalves Resende Ferreira ◽

Andrea Maria Amaral Nascimento ◽

Mariana de Paula Reis ◽

Marcela França Dias ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Wastewater Treatment Plants ◽

Resistance Mechanisms ◽

Full Scale ◽

Diffusion Method ◽

Molecular Method ◽

Resistance Determinants ◽

Antibiotic Resistance Profile ◽

Potential Reservoir

Abstract Wastewater treatment plants (WWTPs) represent an important reservoir of antibiotic resistance determinants. Although many studies have been conducted to evaluate resistance profiles in Enterobacteriaceae isolates from this setting, the dynamics of this phenomenon are poorly known to the bacterium Pseudomonas aeruginosa. Here we aimed to evaluate the resistance profiles and the production of AmpC β-lactamase in P. aeruginosa isolates from a domestic full-scale WWTP. Samples of the raw sewage and effluent were collected and the bacterium P. aeruginosa was isolated on cetrimide agar. Susceptibility to β-lactams, fluoroquinolones and aminoglycosides was evaluated by the disc diffusion method, and the presence of AmpC β-lactamase was investigated phenotypically and by molecular method. We recovered 27 isolates of P. aeruginosa. Of these, 81.5% were susceptible to all antimicrobials tested. However, a considerable rate of resistance to carbapenems (11%) was found among the isolates. Twenty-two isolates were positive in the phenotypic test for inducible AmpC β-lactamase but the blaampc gene was only identified in four isolates, suggesting the presence of other independent resistance mechanisms besides this β-lactamase. In summary, we have shown that P. aeruginosa isolates from a domestic WWTP represents a potential reservoir of blaampC genes and other resistance determinants, including those that result in low susceptibility to carbapenems and aminoglycosides.

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MICROORGANISMS ANTIBIOTIC RESISTANCE MECHANISMS – PRESENT VIEW

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2019-21-10-125-130 ◽

2019 ◽

Vol 21 (10) ◽

pp. 125-130

Author(s):

Пушилина А.Д. ◽

◽

Коменкова Т.С. ◽

Зайцева Е.А. ◽

Keyword(s):

Antibiotic Resistance ◽

Resistance Mechanisms ◽

Present View

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Extracellular DNA (eDNA): Neglected and Potential Sources of Antibiotic Resistant Genes (ARGs) in the Aquatic Environments

Pathogens ◽

10.3390/pathogens9110874 ◽

2020 ◽

Vol 9 (11) ◽

pp. 874

Author(s):

Periyasamy Sivalingam ◽

John Poté ◽

Kandasamy Prabakar

Keyword(s):

Antibiotic Resistance ◽

Health Risk ◽

Genetic Material ◽

Antibiotic Resistance Genes ◽

Extracellular Dna ◽

Antibiotic Resistant ◽

Treatment Technologies ◽

Environmental Bacteria ◽

Global Threat ◽

Potential Public Health

Over the past decades, the rising antibiotic resistance bacteria (ARB) are continuing to emerge as a global threat due to potential public health risk. Rapidly evolving antibiotic resistance and its persistence in the environment, have underpinned the need for more studies to identify the possible sources and limit the spread. In this context, not commonly studied and a neglected genetic material called extracellular DNA (eDNA) is gaining increased attention as it can be one of the significant drivers for transmission of extracellular ARGS (eARGs) via horizontal gene transfer (HGT) to competent environmental bacteria and diverse sources of antibiotic-resistance genes (ARGs) in the environment. Consequently, this review highlights the studies that address the environmental occurrence of eDNA and encoding eARGs and its impact on the environmental resistome. In this review, we also brief the recent dedicated technological advancements that are accelerating extraction of eDNA and the efficiency of treatment technologies in reducing eDNA that focuses on environmental antibiotic resistance and potential ecological health risk.

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Antimicrobials and Food-Related Stresses as Selective Factors for Antibiotic Resistance along the Farm to Fork Continuum

Antibiotics ◽

10.3390/antibiotics10060671 ◽

2021 ◽

Vol 10 (6) ◽

pp. 671

Author(s):

Federica Giacometti ◽

Hesamaddin Shirzad-Aski ◽

Susana Ferreira

Keyword(s):

Antibiotic Resistance ◽

Food Safety ◽

Antimicrobial Resistance ◽

Food Processing ◽

Resistance Mechanisms ◽

Human Environment ◽

Real Risk ◽

Cross Adaptation ◽

Novel Approaches

Antimicrobial resistance (AMR) is a global problem and there has been growing concern associated with its widespread along the animal–human–environment interface. The farm-to-fork continuum was highlighted as a possible reservoir of AMR, and a hotspot for the emergence and spread of AMR. However, the extent of the role of non-antibiotic antimicrobials and other food-related stresses as selective factors is still in need of clarification. This review addresses the use of non-antibiotic stressors, such as antimicrobials, food-processing treatments, or even novel approaches to ensure food safety, as potential drivers for resistance to clinically relevant antibiotics. The co-selection and cross-adaptation events are covered, which may induce a decreased susceptibility of foodborne bacteria to antibiotics. Although the available studies address the complexity involved in these phenomena, further studies are needed to help better understand the real risk of using food-chain-related stressors, and possibly to allow the establishment of early warnings of potential resistance mechanisms.

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