Antibiotic Resistance and Epigenetics: More to It than Meets the Eye

ABSTRACT The discovery of antibiotics in the last century is considered one of the most important achievements in the history of medicine. Antibiotic usage has significantly reduced morbidity and mortality associated with bacterial infections. However, inappropriate use of antibiotics has led to emergence of antibiotic resistance at an alarming rate. Antibiotic resistance is regarded as a major health care challenge of this century. Despite extensive research, well-documented biochemical mechanisms and genetic changes fail to fully explain mechanisms underlying antibiotic resistance. Several recent reports suggest a key role for epigenetics in the development of antibiotic resistance in bacteria. The intrinsic heterogeneity as well as transient nature of epigenetic inheritance provides a plausible backdrop for high-paced emergence of drug resistance in bacteria. The methylation of adenines and cytosines can influence mutation rates in bacterial genomes, thus modulating antibiotic susceptibility. In this review, we discuss a plethora of recently discovered epigenetic mechanisms and their emerging roles in antibiotic resistance. We also highlight specific epigenetic mechanisms that merit further investigation for their role in antibiotic resistance.

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Bloodstream infection with Acinetobacter baumanii in a Plasmodium falciparum positive infant: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-020-02648-7 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Charity Wiafe Akenten ◽

Kennedy Gyau Boahen ◽

Kwadwo Sarfo Marfo ◽

Nimako Sarpong ◽

Denise Dekker ◽

...

Keyword(s):

Case Report ◽

Bacterial Infections ◽

Treatment Options ◽

Female Child ◽

Correct Choice ◽

Blood Cultures ◽

Microbial Culture ◽

Acinetobacter Baumanii ◽

Inappropriate Use ◽

History Of

Abstract Background The increasing incidence of multi-antibiotic-resistant bacterial infections, coupled with the risk of co-infections in malaria-endemic regions, complicates accurate diagnosis and prolongs hospitalization, thereby increasing the total cost of illness. Further, there are challenges in making the correct choice of antibiotic treatment and duration, precipitated by a lack of access to microbial culture facilities in many hospitals in Ghana. The aim of this case report is to highlight the need for blood cultures or alternative rapid tests to be performed routinely in malaria patients, to diagnose co-infections with bacteria, especially when symptoms persist after antimalarial treatment. Case presentation A 6-month old black female child presented to the Agogo Presbyterian Hospital with fever, diarrhea, and a 3-day history of cough. A rapid diagnostic test for malaria and Malaria microscopy was positive for P. falciparum with a parasitemia of 224 parasites/μl. The patient was treated with Intravenous Artesunate, parental antibiotics (cefuroxime and gentamicin) and oral dispersible zinc tablets in addition to intravenous fluids. Blood culture yielded Acinetobacter baumanii, which was resistant to all of the third-generation antibiotics included in the susceptibility test conducted, but sensitive to ciprofloxacin and gentamicin. After augmenting treatment with intravenous ciprofloxacin, all symptoms resolved. Conclusion Even though this study cannot confirm whether the bacterial infection was nosocomial or otherwise, the case highlights the necessity to test malaria patients for possible co-infections, especially when fever persists after parasites have been cleared from the bloodstream. Bacterial blood cultures and antimicrobial susceptibility testing should be routinely performed to guide treatment options for febril illnesses in Ghana in order to reduce inappropriate use of broad-spectrum antibiotics and limit the development of antimicrobial resistance.

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Possibilities of tropical treatment of bacterial ENT infections

Medical Council ◽

10.21518/2079-701x-2021-18-44-54 ◽

2021 ◽

pp. 44-54

Author(s):

P. A. Shamkina ◽

A. A. Krivopalov ◽

P. I. Panchenko ◽

S. V. Ryazantsev

Keyword(s):

Antibiotic Resistance ◽

Otitis Media ◽

Primary Care Physicians ◽

Bacterial Infections ◽

Acute Otitis Media ◽

Medical Community ◽

Antibacterial Drug ◽

Upper Respiratory Tract ◽

Inappropriate Use ◽

Acute Rhinosinusitis

The overuse and inappropriate use of systemic antibiotics is the most serious cause of problems associated with the increasing resistance of bacterial pathogens. What served as the basis for WHO to call the XXI century “The era of antibiotic resistance”. The wide spread of resistant strains of microorganisms, the growth of severe and complicated forms of diseases leads to an increase in the frequency of unfavorable treatment outcomes. In the Russian Federation, an increase in the incidence of acute rhinosinusitis from 4.6 to 12.7 cases per 1000 population has been noted in the last decade. The incidence of acute rhinosinusitis in Europe is recorded in 6.4 ± 3.6 of all cases of visits to primary care physicians. Up to 38% of outpatients in the ENT profile suffer from various forms of otitis media, including up to 30% of acute otitis media. The most important way to overcome the global problem of antibiotic resistance, along with the delayed use of systemic antibacterial drugs initiated by the world medical community, is to switch to the active use of topical drugs with antimicrobial activity. The article provides an overview of the data of domestic and foreign literature on the properties of a topical antibacterial drug with the active ingredient hydroxymethylquinoxaline dioxide. The results of experimental work and clinical studies, proving the high efficacy and safety of the drug in the complex treatment of bacterial infections of the upper respiratory tract, have been analyzed.

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The Association between Insertion Sequences and Antibiotic Resistance Genes

mSphere ◽

10.1128/msphere.00418-20 ◽

2020 ◽

Vol 5 (5) ◽

Cited By ~ 1

Author(s):

Mohammad Razavi ◽

Erik Kristiansson ◽

Carl-Fredrik Flach ◽

D. G. Joakim Larsson

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Bacterial Infections ◽

Antibiotic Resistance Genes ◽

Mobile Genetic Elements ◽

Insertion Sequences ◽

Negative Consequences ◽

Bacterial Genomes ◽

Genetic Elements ◽

Empirical Approaches

ABSTRACT Insertion sequences (ISs) are abundant mobile genetic elements on bacterial genomes, responsible for mobilization of many genes, including antibiotic resistance genes (ARGs). As ARGs often occur in similar genetic contexts, understanding which ISs tend to be associated with known ARGs could be a first step toward discovering novel ARGs through predictive or experimental strategies. This could be valuable, as early identification of ARGs in pathogens could facilitate surveillance, confinement actions, molecular diagnostics, and drug development. Here, we present a comprehensive analysis of the association of specific ISs with known ARGs. A large collection of bacterial genomes was used to characterize the immediate context of 2,437 known ARGs and 3,768 ISs. While many ARGs were consistently found close to specific ISs, the contexts around all ISs were more variable. Nevertheless, a subset of individual ISs, as well as tentative composite transposons, showed significant associations with ARGs. These included, e.g., insertion sequences classified as IS6, Tn3, IS4, and IS1 that were not only strongly associated with diverse ARGs but also highly abundant in pathogens. Therefore, we conclude that the context of this subset of ISs and tentative composite transposons would be particularly valuable to discover novel ARGs through modeling or empirical approaches. A set of 1,891 metagenomes were analyzed to identify environments where those ISs commonly associated with ARGs were particularly abundant. The associations found in metagenomes were similar to those found in genomes. IMPORTANCE The emergence and spread of antibiotic resistance genes (ARGs) among pathogens threaten the prevention and treatment of bacterial infections as well as our food production chains. Early knowledge about mobile ARGs that are present in pathogens or that have the potential to become clinically relevant could help mitigate potential negative consequences. Recently, exploring integron gene cassettes was shown to be successful for identifying novel mobilized ARGs, some of which were already circulating in pathogens. Still, only a subset of ARGs is mobilized by integrons, and the contexts of other mobile genetic elements associated with ARGs remain unexplored. This includes insertion sequences (ISs) responsible for the mobilization of many ARGs. Our analyses identified ISs, species, and environments where ARG-IS relationships are particularly strong. This could be a first step to guide the discovery of novel ARGs, while also providing insights into mechanisms involved in the mobilization and transfer of ARGs.

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Educational Video Improves Knowledge about Outpatients’ Usage of Antibiotics in Two Public Hospitals in Indonesia

Antibiotics ◽

10.3390/antibiotics10050606 ◽

2021 ◽

Vol 10 (5) ◽

pp. 606

Author(s):

Fauna Herawati ◽

Rika Yulia ◽

Bustanul Arifin ◽

Ikhwan Frasetyo ◽

Setiasih ◽

...

Keyword(s):

Antibiotic Resistance ◽

General Hospital ◽

Sampling Technique ◽

Knowledge Score ◽

Antibiotic Use ◽

Public Hospitals ◽

Educational Video ◽

Inappropriate Use ◽

Quasi Experimental ◽

The Difference

The inappropriate use or misuse of antibiotics, particularly by outpatients, increases antibiotic resistance. A lack of public knowledge about “Responsible use of antibiotics” and “How to obtain antibiotics” is a major cause of this. This study aimed to assess the effectiveness of an educational video about antibiotics and antibiotic use to increase outpatients’ knowledge shown in two public hospitals in East Java, Indonesia. A quasi-experimental research setting was used with a one-group pre-test—post-test design, carried out from November 2018 to January 2019. The study population consisted of outpatients to whom antibiotics were prescribed. Participants were selected using a purposive sampling technique; 98 outpatients at MZ General Hospital in the S regency and 96 at SG General Hospital in the L regency were included. A questionnaire was used to measure the respondents’ knowledge, and consisted of five domains, i.e., the definition of infections and antibiotics, obtaining the antibiotics, directions for use, storage instructions, and antibiotic resistance. The knowledge test score was the total score of the Guttman scale (a dichotomous “yes” or “no” answer). To determine the significance of the difference in knowledge before and after providing the educational video and in the knowledge score between hospitals, the (paired) Student’s t-test was applied. The educational videos significantly improved outpatients’ knowledge, which increased by 41% in MZ General Hospital, and by 42% in SG General Hospital. It was concluded that an educational video provides a useful method to improve the knowledge of the outpatients regarding antibiotics.

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Phage-Encoded Endolysins

Antibiotics ◽

10.3390/antibiotics10020124 ◽

2021 ◽

Vol 10 (2) ◽

pp. 124

Author(s):

Fatma Abdelrahman ◽

Maheswaran Easwaran ◽

Oluwasegun I. Daramola ◽

Samar Ragab ◽

Stephanie Lynch ◽

...

Keyword(s):

Clinical Trials ◽

Cell Wall ◽

Antibiotic Resistance ◽

Bacterial Infections ◽

Therapeutic Strategies ◽

Therapeutic Application ◽

Significant Evidence ◽

Crucial Information

Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.

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Silencing Antibiotic Resistance with Antisense Oligonucleotides

Biomedicines ◽

10.3390/biomedicines9040416 ◽

2021 ◽

Vol 9 (4) ◽

pp. 416

Author(s):

Saumya Jani ◽

Maria Soledad Ramirez ◽

Marcelo E. Tolmasky

Keyword(s):

Antibiotic Resistance ◽

Nucleic Acids ◽

Antisense Oligonucleotides ◽

Bacterial Infections ◽

Genetic Disorders ◽

Antibiotic Resistance Genes ◽

Short Review ◽

Rnase H ◽

Biological Processes ◽

Locked Nucleic Acids

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeting resistance to β-lactams include carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones. The purpose of this short review is to summarize the attempts to develop antisense compounds that inhibit expression of resistance to antibiotics.

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Draft Genome Sequence of a Clinically Isolated Extensively Drug-Resistant Pseudomonas aeruginosa Strain

Genome Announcements ◽

10.1128/genomea.00162-16 ◽

2016 ◽

Vol 4 (2) ◽

Author(s):

Bhavani Manivannan ◽

Niranjana Mahalingam ◽

Sudhir Jadhao ◽

Amrita Mishra ◽

Pravin Nilawe ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Genome Assembly ◽

Biofilm Formation ◽

Draft Genome ◽

Drug Resistant ◽

Draft Genome Assembly ◽

Extensively Drug Resistant ◽

History Of ◽

Urinary Tuberculosis

We present the draft genome assembly of an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain isolated from a patient with a history of genito urinary tuberculosis. The draft genome is 7,022,546 bp with a G+C content of 65.48%. It carries 7 phage genomes, genes for quorum sensing, biofilm formation, virulence, and antibiotic resistance.

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Recent Development of Rapid Antimicrobial Susceptibility Testing Methods through Metabolic Profiling of Bacteria

Antibiotics ◽

10.3390/antibiotics10030311 ◽

2021 ◽

Vol 10 (3) ◽

pp. 311

Author(s):

Chen Chen ◽

Weili Hong

Keyword(s):

Antimicrobial Susceptibility ◽

Metabolic Profiling ◽

Bacterial Infections ◽

Susceptibility Testing ◽

Antimicrobial Susceptibility Testing ◽

Bacterial Metabolism ◽

Resistant Bacteria ◽

Bacterial Cells ◽

Inappropriate Use ◽

Key Factor

Due to the inappropriate use and overuse of antibiotics, the emergence and spread of antibiotic-resistant bacteria are increasing and have become a major threat to human health. A key factor in the treatment of bacterial infections and slowing down the emergence of antibiotic resistance is to perform antimicrobial susceptibility testing (AST) of infecting bacteria rapidly to prescribe appropriate drugs and reduce the use of broad-spectrum antibiotics. Current phenotypic AST methods based on the detection of bacterial growth are generally reliable but are too slow. There is an urgent need for new methods that can perform AST rapidly. Bacterial metabolism is a fast process, as bacterial cells double about every 20 to 30 min for fast-growing species. Moreover, bacterial metabolism has shown to be related to drug resistance, so a comparison of differences in microbial metabolic processes in the presence or absence of antimicrobials provides an alternative approach to traditional culture for faster AST. In this review, we summarize recent developments in rapid AST methods through metabolic profiling of bacteria under antibiotic treatment.

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Bacteria and Their Antibiotic Resistance Profiles in Ambient Air in Accra, Ghana, February 2020: A Cross-Sectional Study

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6030110 ◽

2021 ◽

Vol 6 (3) ◽

pp. 110

Author(s):

Godfred Saviour Kudjo Azaglo ◽

Mohammed Khogali ◽

Katrina Hann ◽

John Alexis Pwamang ◽

Emmanuel Appoh ◽

...

Keyword(s):

Antibiotic Resistance ◽

Pathogenic Bacteria ◽

Ambient Air ◽

Cross Sectional Study ◽

Bacillus Species ◽

Resistant Bacteria ◽

Cross Sectional ◽

Antibiotic Resistant ◽

Bacterial Counts ◽

Inappropriate Use

Inappropriate use of antibiotics has led to the presence of antibiotic-resistant bacteria in ambient air. There is no published information about the presence and resistance profiles of bacteria in ambient air in Ghana. We evaluated the presence and antibiotic resistance profiles of selected bacterial, environmental and meteorological characteristics and airborne bacterial counts in 12 active air quality monitoring sites (seven roadside, two industrial and three residential) in Accra in February 2020. Roadside sites had the highest median temperature, relative humidity, wind speed and PM10 concentrations, and median airborne bacterial counts in roadside sites (115,000 CFU/m3) were higher compared with industrial (35,150 CFU/m3) and residential sites (1210 CFU/m3). Bacillus species were isolated in all samples and none were antibiotic resistant. There were, however, Pseudomonas aeruginosa, Escherichia coli, Pseudomonas species, non-hemolytic Streptococci, Coliforms and Staphylococci species, of which six (50%) showed mono-resistance or multidrug resistance to four antibiotics (penicillin, ampicillin, ciprofloxacin and ceftriaxone). There was a positive correlation between PM10 concentrations and airborne bacterial counts (rs = 0.72), but no correlations were found between PM10 concentrations and the pathogenic bacteria nor their antibiotic resistance. We call for the expansion of surveillance of ambient air to other cities of Ghana to obtain nationally representative information.

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Sequence variation and evolution of nuclear DNA in man and the primates

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1981.0021 ◽

1981 ◽

Vol 292 (1057) ◽

pp. 133-142 ◽

Cited By ~ 5

Keyword(s):

Dna Sequence ◽

Sequence Variation ◽

Nuclear Dna ◽

Sequence Divergence ◽

Gene Arrangement ◽

Human Populations ◽

Genetic Changes ◽

Detailed Structural Analysis ◽

Dna Sequence Variation ◽

History Of

Recent advances in nucleic acid technology have facilitated the detection and detailed structural analysis of a wide variety of genes in higher organisms, including those in man. This in turn has opened the way to an examination of the evolution of structural genes and their surrounding and intervening sequences. In a study of the evolution of haemoglobin genes and neighbouring sequences in man and the primates, we have investigated gene arrangement and DNA sequence divergence both within and between species ranging from Old World monkeys to man. This analysis is beginning to reveal the evolutionary constraints that have acted on this region of the genome during primate evolution. Furthermore, DNA sequence variation, both within and between species, provides, in principle, a novel and powerful method for determining inter-specific phylogenetic distances and also for analysing the structure of present-day human populations. Application of this new branch of molecular biology to other areas of the human genome should prove important in unravelling the history of genetic changes that have occurred during the evolution of man.

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