Antibiotic resistance in the environment

"Want a better way to control antibiotic resistance? Fight the corruption." Pathogens and Global Health, 109(4), pp. 168–169

Spatial distribution of antibiotic and heavy metal resistance genes in the Black Sea

This article provides an overview of scientific studies on the problem of microbial resistance to antibiotics. It summarizes current concepts of antibiotic resistance, the division of microorganisms into sensitive and resistant to antibiotics, and explains the concept of minimal inhibitory concentration from a modern perspective. The main mechanisms of the development of antibiotic resistance, vectors, and genes responsible for the transmission of resistance are revealed. Microorganism resistance to antibacterial agents can be innate or acquired. The bacterial pathogens of respiratory infections, such as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, and other gram-positive and gram-negative bacteria, are described. Non-hereditary resistance mechanisms are shown, including changes in metabolic activity, phenotypic plasticity, and biofilm formation. The factors involved in the acquisition and transmission of antibiotic resistance, as well as the evolution of antibiotic resistance, which goes through several key stages, are discussed. One of the vectors in studying the evolution of antibiotic resistance should be the analysis of bacterial communities forming biofilms rather than isolated bacterial strains, as microorganisms in biofilms exhibit low sensitivity to various antibiotics due to phenotypic resistance mechanisms.The methods of combating antibiotic resistance include several approaches: rational use of antibiotics, development of new antibiotics, and vaccination

INTRODUCTION: Solution to the problem of antibiotic resistance (ABR) and the continuing spread of multidrug resistant strains is a strategic task of practical healthcare. An important tool for improving antimicrobial pharmacotherapy, along with active search for new effective drug compounds, can be a detailed investigation of the prime cause of the emergence and effect of the extracellular environment on the molecular mechanisms of bacterial resistance to chemotherapeutic drugs. AIM: Analysis of the literature devoted to the molecular mechanisms of antimicrobial defense strategy of the bacterial cell against the effect of medical drugs, and to promising strategies of combating antibiotic-resistant agents. MATERIALS AND METHODS: A search and analysis of the scientific literature was conducted in PubMed, eLibrary, Europe PMC, WoS, CyberLeninka and other databases for the last 5 years. The search queries included the following word combinations: for Russian-language publications the problem of ABR, environmental factors of antibiotic sensitivity, resistance mechanisms, resistance genes, mobile genetic elements; for English-language publications: antibiotic resistance evolution, antibiotic resistance genes, antibiotic resistance in biofilms, transmission of antibiotic resistance. A total of 100 literature sources published from 2018 to 2022 have been analyzed, of which 44 were included in the review. An analysis of domestic and foreign sources showed that a significant role in the development of ABR in microorganisms is assigned to enzymatic beta-lactamase activity, specific protective proteins of microorganisms, as well as the ability of pathogenic strains to form biofilms. Besides, according to the results of studies, the main source of resistance genes is the environment, where the transfer of ABR genes between representatives of different bacterial taxa occurs. Promising areas in the fight against antibiotic-resistant pathogens are mathematical modeling, synthetic biology, phage therapy. CONCLUSION: In modern studies, the tendency of microorganisms to ABR presents a serious evolutionary and ecological problem. The uncontrolled and unjustified current use of antibacterial drugs in medicine, veterinary medicine and agriculture provoked the activation of the mechanisms of bacterial cell defense known by the moment, and caused enhancement of the adaptive capacity of bacterial pathogens and spread of multidrug resistant strains. The review also provides data on various strategies aimed at solving the ABR problem.

PurposeQuality use of antibiotics and the development of antibiotic resistance is a global catastrophe. In the conceptual context, the phenomenon is correlated with the healthcare practitioners’ understanding of antibiotic use and resistance. Therefore, the study aimed to highlight nurses’ perception of antibiotic use and resistance at a public healthcare institute in Quetta City, Pakistan.Respondents and MethodsBy using a semi-structured interview guide through the phenomenology-based approach, in-depth, face-to-face interviews were conducted. Nurses practicing at the surgical and medical units of Sandeman Provincial Hospital (SPH), Quetta, were approached for the study. All interviews were audio-taped, transcribed verbatim, and were then analyzed for thematic contents by the standard content analysis framework.ResultsAlthough the saturation was reached after the 13th interview, an additional two were interviewed for absolute validation. Content analysis revealed five major themes: (1) defining antibiotics and antibiotic resistance, (2) antibiotic use: awareness and concern, (3) antimicrobial resistance: awareness and concern, (4) responding to antibiotic use and resistance, and (5) barriers to quality use of antibiotics and prevention of antibiotic resistance. Even though the understanding of nurses regarding antibiotic use and resistance was promising, certain apprehensions were also observed. The respondents were aware of the critical situation and provided valuable insights that can offer significant input while promoting the quality use of antibiotics in a developing country.ConclusionWhile the perception towards antibiotics appeared positive, potential areas of concern and contributing factors regarding antibiotic resistance were also identified. Importantly, nurses too highlighted possible solutions to address the issue of irrational antibiotic use and the development of antibiotic resistance.

Impact of biofilm formation and detachment on the transmission of bacterial antibiotic resistance in drinking water distribution systems

A group of coagulase-negative staphylococci (CoNS) was historically classified as a nonpathogenic bacteria. Over the last few decades, nosocomial infections caused by CoNS as opportunistic pathogens have increased and become one of the major nosocomial pathogens. The aim of this study was to identify the relationship between the use of an antibiotic agent for CoNS in Bali’s regional public hospital and the development of antibiotic resistance during 3 years period. This study was a retrospective ecological study of antibiotic resistance and antibiotic consumption secondary data collected prospectively. It was conducted over a three years period of inpatient data. Susceptibility of CoNS to antibiotics was obtained from the hospital antibiogram of all isolates from 2017 to 2019. Sensitivity results in antibiogram were based on the standards provided by the Clinical and Laboratory Standards Institute (CLSI) with the disk diffusion method. Antibiotic consumption in DDDs/100 bed-days. The relationships between DDDs/100 bed-days of each antibiotic and rates of antibiotic resistance of each resistant strain of CoNS were tested using Spearman correlation and logistic regression. There was no significant correlation between antibiotic consumption (DDD) and the percentage of antibiotic resistance among the three CoNS species (p>0.05). However, this study found there was an inverse relationship between DDD and antibiotic resistance in Staphylococcus hominis species (OR = 0.063; CI [0.004-0.915]; p=0.043). We conclude that no significant correlation between antibiotic consumption and antibiotic resistance of the 3 CoNS species. There needs to be further research to identify antibiotic consumption, antibiotic resistance and other factors affecting antibiotic resistance.

Chapter 8 - Combination of virulence and antibiotic resistance: a successful bacterial strategy to survive under hostile environments

Nussbaum’s capability theory by drawing attention to multiple determinants of wellbeing provides a rich and relevant evaluative space for framing antibiotic resistance. I consider the implications of antibiotic resistance for child development and adult capabilities. There are common risk factors for childhood growth stunting and the spread of infectious diseases in both antibiotic sensitive and resistant forms. The interaction between infectious diseases, antibiotic resistance and growth stunting illustrates a clustering of disadvantage. The control of antibiotic resistance requires wide-ranging cooperative action. Cooperation is predicated on an expectation of equitable access to effective antibiotics. This expectation is confounded by inequality both in access to antibiotics, and in the risk that available antibiotics will be ineffective. Securing child development (and adult capabilities) requires that inequalities both in access to antibiotics and in risk factors for the dissemination and transmission of antibiotic resistance are addressed. Inequality undermines the cooperative activity that is control of infectious diseases and compounds the threat to the securing of capabilities that arises from antibiotic resistance.

As recognized by several international agencies, antibiotic resistance is nowadays one of the most relevant problems for human health. While this problem was alleviated with the introduction of new antibiotics into the market in the golden age of antimicrobial discovery, nowadays few antibiotics are in the pipeline. Under these circumstances, a deep understanding on the mechanisms of emergence, evolution and transmission of antibiotic resistance, as well as on the consequences for the bacterial physiology of acquiring resistance is needed to implement novel strategies, beyond the development of new antibiotics or the restriction in the use of current ones, to more efficiently treat infections. There are still several aspects in the field of antibiotic resistance that are not fully understood. In the current article, we make a non-exhaustive critical review of some of them that we consider of special relevance, in the aim of presenting a snapshot of the studies that still need to be done to tackle antibiotic resistance.

Antibiotics and antibiotic resistance genes in landfills: A review

The widespread use of antibiotics in animals is causing concerns about the growing risk for development and the spread of antibiotic-resistant bacteria. Antibiotic consumption is higher in animals than in humans as reported in a joint publication of EFSA (European Food Safety Agency), ECDC (European Centre for Disease Prevention and Control), and EMA (European Medicines Agency) using data from 2011 and 2012. Both in humans and animals, positive associations between the consumption of antibiotics and resistant bacteria are observed. Responsible use of antibiotics in humans and animals should therefore be promoted. In this paper some general aspects of antibiotic resistance such as microbiological versus clinical resistance, intrinsic versus acquired resistance, resistance mechanisms, and transfer of resistance are briefly introduced. In 2012, the Belgian Center of Expertise on Antimicrobial Consumption and Resistance in Animals (AMCRA) was founded. Its mission is to collect and analyze all data related to antibiotic use and resistance in animals in Belgium and to communicate these findings in a neutral and objective manner. One of AMCRA's 10 objectives is a 50% reduction in antibiotic consumption in veterinary medicine in Belgium by 2020. The aim of this paper is to report on the achievements of this national project. The Institute for Agricultural and Fisheries Research (ILVO, Merelbeke-Melle), in collaboration with Ghent University, is currently working on three nationally funded projects on antibiotic resistance in animal husbandry. In the first project, an in vitro model is used to study the influence of low antibiotic concentrations due to carry-over after production and usage of medicated feed on the development of resistance in the pig gut. Part of that project is to develop a quantitative risk assessment model. A second project focuses on tracking excreted antibiotics used in pig rearing and their influence on the development of antibiotic resistance in pig manure and the environment. In the last project, the relation between the use of biocides in animal husbandry and antibiotic resistance development are being studied. Copyright © 2016 John Wiley & Sons, Ltd.

Irrational antibiotic use contributes to the development of antibiotic resistance in bacteria, which is a major cause of healthcare-associated infections globally. Molecular research has shown that multiple resistance frequently develops from the uptake of pre-existing resistance genes, which are subsequently intensified under selective pressures. Resistant genes spread and are acquired through mobile genetic elements which are essential for facilitating horizontal gene transfer. MGEs have been identified as carriers of genetic material and are a significant player in evolutionary processes. These include insertion sequences, transposons, integrative and conjugative elements, plasmids, and genomic islands, all of which can transfer between and within DNA molecules. With an emphasis on pathogenic bacteria, this review highlights the salient features of the MGEs that contribute to the development and spread of antibiotic resistance. MGEs carry non-essential genes, including AMR and virulence genes, which can enhance the adaptability and fitness of their bacterial hosts. These elements employ evolutionary strategies to facilitate their replication and dissemination, thus enabling survival without positive selection for the harboring of beneficial genes.

We used quantitative microbial risk assessment to estimate ingestion risk for intI1, erm(B), sul1, tet(A), tet(W), and tet(X) in private wells contaminated by human and/or livestock feces. Genes were quantified with five human-specific and six bovine-specific microbial source-tracking (MST) markers in 138 well-water samples from a rural Wisconsin county. Daily ingestion risk (probability of swallowing ≥1 gene) was based on daily water consumption and a Poisson exposure model. Calculations were stratified by MST source and soil depth over the aquifer where wells were drilled. Relative ingestion risk was estimated using wells with no MST detections and >6.1 m soil depth as a referent category. Daily ingestion risk varied from 0 to 8.8 × 10-1 by gene and fecal source (i.e., human or bovine). The estimated number of residents ingesting target genes from private wells varied from 910 (tet(A)) to 1,500 (intI1 and tet(X)) per day out of 12,000 total. Relative risk of tet(A) ingestion was significantly higher in wells with MST markers detected, including wells with ≤6.1 m soil depth contaminated by bovine markers (2.2 [90% CI: 1.1-4.7]), wells with >6.1 m soil depth contaminated by bovine markers (1.8 [1.002-3.9]), and wells with ≤6.1 m soil depth contaminated by bovine and human markers simultaneously (3.1 [1.7-6.5]). Antibiotic resistance genes (ARGs) were not necessarily present in viable microorganisms, and ingestion is not directly associated with infection. However, results illustrate relative contributions of human and livestock fecal sources to ARG exposure and highlight rural groundwater as a significant point of exposure.IMPORTANCEAntibiotic resistance is a global public health challenge with well-known environmental dimensions, but quantitative analyses of the roles played by various natural environments in transmission of antibiotic resistance are lacking, particularly for drinking water. This study assesses risk of ingestion for several antibiotic resistance genes (ARGs) and the class 1 integron gene (intI1) in drinking water from private wells in a rural area of northeast Wisconsin, United States. Results allow comparison of drinking water as an exposure route for antibiotic resistance relative to other routes like food and recreational water. They also enable a comparison of the importance of human versus livestock fecal sources in the study area. Our study demonstrates the previously unrecognized importance of untreated rural drinking water as an exposure route for antibiotic resistance and identifies bovine fecal material as an important exposure factor in the study setting.

The rapid horizontal transmission of antibiotic resistance genes on conjugative plasmids between bacterial host cells is a major cause of the accelerating antibiotic resistance crisis. There are currently no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation, which prevents understanding and targeting conjugation. We introduce a novel experimental framework to screen for conjugation-based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. Plasmid-carrying donor strains are constructed in high-throughput. We then mix the resistance plasmid-carrying donors with recipients in a design where only transconjugants can reproduce, measure growth in dense intervals, and extract transmission times as the growth lag. As proof-of-principle, we exhaustively explore chromosomal genes controlling F-plasmid donation within Escherichia coli populations, by screening the Keio deletion collection in high replication. We recover all seven known chromosomal gene mutants affecting conjugation as donors and identify many novel mutants, all of which diminish antibiotic resistance transmission. We validate nine of the novel genes' effects in liquid mating assays and complement one of the novel genes' effect on conjugation (rseA). The new framework holds great potential for exhaustive disclosing of candidate targets for helper drugs that delay resistance development in patients and societies and improve the longevity of current and future antibiotics. Further, the platform can easily be adapted to explore interspecies conjugation, plasmid-borne factors, and experimental evolution and be used for rapid construction of strains.IMPORTANCE The rapid transmission of antibiotic resistance genes on conjugative plasmids between bacterial host cells is a major cause of the accelerating antibiotic resistance crisis. There are currently no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation, which prevents understanding and targeting conjugation. We introduce a novel experimental framework to screen for conjugation-based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. As proof-of-principle, we exhaustively explore chromosomal genes controlling F-plasmid donation within E. coli populations. We recover all previously known and many novel chromosomal gene mutants that affect conjugation efficiency. The new framework holds great potential for rapid screening of compounds that decrease transmission. Further, the platform can easily be adapted to explore interspecies conjugation, plasmid-borne factors, and experimental evolution and be used for rapid construction of strains.