-
Chemical Communications (Cambridge,... May 2023Antibiotic resistance is an enormous problem that is accountable for over a million deaths annually, with numbers expected to significantly increase over the coming... (Review)
Review
Antibiotic resistance is an enormous problem that is accountable for over a million deaths annually, with numbers expected to significantly increase over the coming decades. Although some of the underlying causes leading up to antibiotic resistance are well understood, many of the molecular processes involved remain elusive. To better appreciate at a molecular level how resistance emerges, customized chemical biology tools can offer a solution. This Feature Article attempts to provide an overview of the wide variety of tools that have been developed over the last decade, by highlighting some of the more illustrative examples. These include the use of fluorescent, photoaffinity and activatable antibiotics and bacterial components to start to unravel the molecular mechanisms involved in resistance. The antibiotic crisis is an eminent global threat and requires the continuous development of creative chemical tools to dissect and ultimately counteract resistance.
Topics: Drug Resistance, Microbial; Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial
PubMed: 37039397
DOI: 10.1039/d3cc00759f -
Cell Host & Microbe Apr 2020Horizontal gene transfer (HGT) facilitates spead of antibiotic resistance elements. In this issue of Cell Host & Microbe, Domenech et al. discover that compounds...
Horizontal gene transfer (HGT) facilitates spead of antibiotic resistance elements. In this issue of Cell Host & Microbe, Domenech et al. discover that compounds disrupting proton motive force block natural competence (COM) and interrupt intraspecies HGT and exchange of antibiotic resistance. Such strategies might minimize clinical spread of antibiotic resistance.
Topics: Bacteria; Drug Resistance, Microbial; Gene Transfer, Horizontal; Plasmids; Proton-Motive Force
PubMed: 32272070
DOI: 10.1016/j.chom.2020.03.013 -
Current Opinion in Microbiology Oct 2023Bacterial pathogens are constantly evolving new resistance mechanisms against antibiotics; hence, strategies to potentiate existing antibiotics or combat mechanisms of... (Review)
Review
Bacterial pathogens are constantly evolving new resistance mechanisms against antibiotics; hence, strategies to potentiate existing antibiotics or combat mechanisms of resistance using adjuvants are always in demand. Recently, inhibitors have been identified that counteract enzymatic modification of the drugs isoniazid and rifampin, which have implications in the study of multi-drug-resistant mycobacteria. A wealth of structural studies on efflux pumps from diverse bacteria has also fueled the design of new small-molecule and peptide-based agents to prevent the active transport of antibiotics. We envision that these findings will inspire microbiologists to apply existing adjuvants to clinically relevant resistant strains, or to use described platforms to discover novel antibiotic adjuvant scaffolds.
Topics: Bacteria; Anti-Bacterial Agents; Drug Resistance, Microbial; Biological Transport; Drug Resistance, Multiple, Bacterial
PubMed: 37329679
DOI: 10.1016/j.mib.2023.102334 -
Frontiers in Cellular and Infection... 2021
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Phylogeny; Virulence; Virulence Factors
PubMed: 33869085
DOI: 10.3389/fcimb.2021.654283 -
MBio Jun 2022Bacteria have evolved to develop multiple strategies for antibiotic resistance by effectively reducing intracellular antibiotic concentrations or antibiotic binding...
Bacteria have evolved to develop multiple strategies for antibiotic resistance by effectively reducing intracellular antibiotic concentrations or antibiotic binding affinities, but the role of cell morphology in antibiotic resistance remains poorly understood. By analyzing cell morphological data for different bacterial species under antibiotic stress, we find that bacteria increase or decrease the cell surface-to-volume ratio depending on the antibiotic target. Using quantitative modeling, we show that by reducing the surface-to-volume ratio, bacteria can effectively reduce the intracellular antibiotic concentration by decreasing antibiotic influx. The model further predicts that bacteria can increase the surface-to-volume ratio to induce the dilution of membrane-targeting antibiotics, in agreement with experimental data. Using a whole-cell model for the regulation of cell shape and growth by antibiotics, we predict shape transformations that bacteria can utilize to increase their fitness in the presence of antibiotics. We conclude by discussing additional pathways for antibiotic resistance that may act in synergy with shape-induced resistance.
Topics: Anti-Bacterial Agents; Bacteria; Cell Shape; Drug Resistance, Bacterial; Drug Resistance, Microbial
PubMed: 35616332
DOI: 10.1128/mbio.00659-22 -
Journal of the European Academy of... Jan 2021Antibiotic resistance in acne was first observed in the 1970s and has been a major concern in dermatology since the 1980s. The resistance rates and types of... (Review)
Review
Antibiotic resistance in acne was first observed in the 1970s and has been a major concern in dermatology since the 1980s. The resistance rates and types of antimicrobials have subsequently shown great variations in regions and countries. Illustrative of this is the resistance to topical erythromycin and clindamycin which continues to be a problem worldwide, while resistance to systemic treatment with tetracyclines has remained low during the past decade. The resistance for the newer macrolides like azithromycin and clarithromycin has been increasing. The results of antibiotic resistance may include treatment failure of acne, disturbance of skin microbiota, induction of opportunistic pathogens locally and systemically, and dissemination of resistant strains to both healthcare personnel and the general population. The ensuing complications, such as aggravated opportunistic infections caused by Propionibacterium acnes and the emergence of multiresistant superbugs, have not yet been confirmed.
Topics: Acne Vulgaris; Anti-Bacterial Agents; Clindamycin; Drug Resistance, Bacterial; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Propionibacterium acnes
PubMed: 32474948
DOI: 10.1111/jdv.16686 -
Trends in Microbiology Sep 2022Biofilms are communities of bacteria forming high-density sessile colonies. Such a lifestyle comes associated with costs and benefits: while the growth rate of biofilms... (Review)
Review
Biofilms are communities of bacteria forming high-density sessile colonies. Such a lifestyle comes associated with costs and benefits: while the growth rate of biofilms is often lower than that of their free-living counterparts, this cost is readily repaid once the colony is subjected to antibiotics. Biofilms can grow in antibiotic concentrations a thousand times higher than planktonic bacteria. While numerous mechanisms have been proposed to explain biofilm recalcitrance towards antibiotics, little is yet known about their effect on the evolution of resistance. We synthesize the current understanding of biofilm recalcitrance from a pharmacodynamic and a population genetics perspective. Using the pharmacodynamic framework, we discuss the effects of various mechanisms and show that biofilms can either promote or impede resistance evolution.
Topics: Anti-Bacterial Agents; Bacteria; Biofilms; Drug Resistance, Microbial; Genetics, Population; Microbial Sensitivity Tests; Plankton
PubMed: 35337697
DOI: 10.1016/j.tim.2022.02.005 -
Environmental Pollution (Barking, Essex... Nov 2023The surge of Antibiotic Resistant Bacteria (ARB) in the environment is poised to be the next health threat. World Health Organisation's (WHO's) Global Antimicrobial...
The surge of Antibiotic Resistant Bacteria (ARB) in the environment is poised to be the next health threat. World Health Organisation's (WHO's) Global Antimicrobial Surveillance System (GLASS) report indicates that developing countries may be at a greater risk. Among various factors, the major driver here could be untreated wastewater and poor sanitation. Bacteria are extremely adaptable to their surroundings and develop Antimicrobial Resistance (AMR) when exposed to antibiotics and other pollutants that cause microbial stress. Thus, untreated domestic wastewater drains could easily become hotspots for the occurrence of ARBs. This study reports surveillance of sewage-carrying drains across four urban cities in India and demonstrated the presence of ARBs in the bacterial community against 7 classes of antibiotics, namely, β-Lactams, Chloramphenicol, Glycopeptides, Macrolides, Tetracycline, Third Generation Cephalosporin, and Quinolones. Untreated domestic wastewater flowing in target drains was collected twice a month, for a period of six months and the microbial community was subjected to Antibiotic Susceptibility Testing (AST) by plate assays. The zone of inhibition was recorded and interpreted as per the interpretive chart of The Clinical & Laboratory Standards Institute (CLSI) & The European Committee on Antimicrobial Susceptibility Testing (EUCAST). The total number of samples showing resistance against antibiotics was used to define an Antibiotic Resistance Index (ARI), calculated for all 20 sampling sites (drains). Results demonstrated that the highest ARI was observed in Delhi and Mumbai, ranging from 0.81 to 0.92 in Delhi and 0.49-0.56 in Mumbai. This surveillance study reveals the antibiotic resistance pattern of the representative bacterial community in the drains and goes beyond few targeted bacterial species. The alarming presence of antibiotic resistant bacterial community highlights the concern of ARBs being the next looming health threat. This report aims to demonstrates the importance of considering sewage surveillance on routine basis by state authorities.
Topics: Wastewater; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Drug Resistance, Microbial; Bacteria; Drug Resistance, Bacterial
PubMed: 37741538
DOI: 10.1016/j.envpol.2023.122586 -
Biochemistry. Biokhimiia Nov 2020This issue of the Biochemistry (Moscow) journal presents reviews and experimental articles on the new strategies for solving the problem of antibiotic resistance and on...
This issue of the Biochemistry (Moscow) journal presents reviews and experimental articles on the new strategies for solving the problem of antibiotic resistance and on the search for novel antimicrobial preparations using the methods of molecular biology, genetics, and nanotechnology. A wide variety of scientific approaches and successful (as a rule) research results give hope for overcoming microbial antibiotic resistance in the fight against infectious diseases.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Microbial; Humans
PubMed: 33280573
DOI: 10.1134/S0006297920110012 -
Ecotoxicology and Environmental Safety Apr 2023Antibiotic resistance is currently one of the greatest threats to human health. Widespread use and residues of antibiotics in humans, animals, and the environment can... (Review)
Review
Antibiotic resistance is currently one of the greatest threats to human health. Widespread use and residues of antibiotics in humans, animals, and the environment can exert selective pressure on antibiotic resistance bacteria (ARB) and antibiotic resistance gene (ARG), accelerating the flow of antibiotic resistance. As ARG spreads to the population, the burden of antibiotic resistance in humans increases, which may have potential health effects on people. Therefore, it is critical to mitigate the spread of antibiotic resistance to humans and reduce the load of antibiotic resistance in humans. This review briefly described the information of global antibiotic consumption information and national action plans (NAPs) to combat antibiotic resistance and provided a set of feasible control strategies for the transmission of ARB and ARG to humans in three areas including (a) Reducing the colonization capacity of exogenous ARB, (b) Enhancing human colonization resistance and mitigating the horizontal gene transfer (HGT) of ARG, (c) Reversing ARB antibiotic resistance. With the hope of achieving interdisciplinary one-health prevention and control of bacterial resistance.
Topics: Animals; Humans; Bacteria; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Genes, Bacterial; Anti-Bacterial Agents; Drug Resistance, Microbial; Drug Resistance, Bacterial
PubMed: 36950985
DOI: 10.1016/j.ecoenv.2023.114734