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Current Opinion in Microbiology Oct 2019The first antibiotic, salvarsan, was deployed in 1910. In just over 100 years antibiotics have drastically changed modern medicine and extended the average human... (Review)
Review
The first antibiotic, salvarsan, was deployed in 1910. In just over 100 years antibiotics have drastically changed modern medicine and extended the average human lifespan by 23 years. The discovery of penicillin in 1928 started the golden age of natural product antibiotic discovery that peaked in the mid-1950s. Since then, a gradual decline in antibiotic discovery and development and the evolution of drug resistance in many human pathogens has led to the current antimicrobial resistance crisis. Here we give an overview of the history of antibiotic discovery, the major classes of antibiotics and where they come from. We argue that the future of antibiotic discovery looks bright as new technologies such as genome mining and editing are deployed to discover new natural products with diverse bioactivities. We also report on the current state of antibiotic development, with 45 drugs currently going through the clinical trials pipeline, including several new classes with novel modes of action that are in phase 3 clinical trials. Overall, there are promising signs for antibiotic discovery, but changes in financial models are required to translate scientific advances into clinically approved antibiotics.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Discovery; History, 20th Century; History, 21st Century; Humans
PubMed: 31733401
DOI: 10.1016/j.mib.2019.10.008 -
Frontiers in Cellular and Infection... 2022Both, antibiotic persistence and antibiotic resistance characterize phenotypes of survival in which a bacterial cell becomes insensitive to one (or even) more... (Review)
Review
Both, antibiotic persistence and antibiotic resistance characterize phenotypes of survival in which a bacterial cell becomes insensitive to one (or even) more antibiotic(s). However, the molecular basis for these two antibiotic-tolerant phenotypes is fundamentally different. Whereas antibiotic resistance is genetically determined and hence represents a rather stable phenotype, antibiotic persistence marks a transient physiological state triggered by various stress-inducing conditions that switches back to the original antibiotic sensitive state once the environmental situation improves. The molecular basics of antibiotic resistance are in principle well understood. This is not the case for antibiotic persistence. Under all culture conditions, there is a stochastically formed, subpopulation of persister cells in bacterial populations, the size of which depends on the culture conditions. The proportion of persisters in a bacterial population increases under different stress conditions, including treatment with bactericidal antibiotics (BCAs). Various models have been proposed to explain the formation of persistence in bacteria. We recently hypothesized that all physiological culture conditions leading to persistence converge in the inability of the bacteria to re-initiate a new round of DNA replication caused by an insufficient level of the initiator complex ATP-DnaA and hence by the lack of formation of a functional orisome. Here, we extend this hypothesis by proposing that in this persistence state the bacteria become more susceptible to mutation-based antibiotic resistance provided they are equipped with error-prone DNA repair functions. This is - in our opinion - in particular the case when such bacterial populations are exposed to BCAs.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Drug Resistance, Microbial
PubMed: 35928205
DOI: 10.3389/fcimb.2022.900848 -
Frontiers in Cellular and Infection... 2020Infectious diseases are the second most important cause of human death worldwide; is a very common human pathogenic microorganism that can trigger a variety of... (Review)
Review
Infectious diseases are the second most important cause of human death worldwide; is a very common human pathogenic microorganism that can trigger a variety of infectious diseases, such as skin and soft tissue infections, endocarditis, osteomyelitis, bacteremia, and lethal pneumonia. Moreover, according to the sensitivity to antibiotic drugs, can be divided into methicillin-sensitive (MSSA) and methicillin-resistant (MRSA). In recent decades, due to the evolution of bacteria and the abuse of antibiotics, the drug resistance of has gradually increased, the infection rate of MRSA has increased worldwide, and the clinical anti-infective treatment for MRSA has become more difficult. Accumulating evidence has demonstrated that the resistance mechanisms of are very complex, especially for MRSA, which is resistant to many kinds of antibiotics. Therefore, understanding the drug resistance of MRSA in a timely manner and elucidating its drug resistance mechanism at the molecular level are of great significance for the treatment of infection. A large number of researchers believe that analyzing the molecular characteristics of can help provide a basis for designing effective prevention and treatment measures against hospital infections caused by and further monitor the evolution of . This paper reviews the research status of MSSA and MRSA, the detailed mechanisms of the intrinsic antibiotic resistance and the acquired antibiotic resistance, the advanced research on anti-MRSA antibiotics and novel therapeutic strategies for MRSA treatment.
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Humans; Methicillin-Resistant Staphylococcus aureus; Prevalence; Staphylococcal Infections; Staphylococcus aureus
PubMed: 32257966
DOI: 10.3389/fcimb.2020.00107 -
British Journal of Biomedical Science 2023Antimicrobial resistance (AMR) has now emerged as a chronic public health problem globally, with the forecast of 10 million deaths per year globally by 2050. AMR occurs... (Review)
Review
Antimicrobial resistance (AMR) has now emerged as a chronic public health problem globally, with the forecast of 10 million deaths per year globally by 2050. AMR occurs when viruses, bacteria, fungi and parasites do not respond to antimicrobial treatments in humans and animals, thus allowing the survival of the microorganism within the host. The prominent cause contributing to the current crisis remains to be the overuse and misuse of antimicrobials, particularly the inappropriate usage of antibiotics, increasing the global burden of antimicrobial resistance. The global consumption and usage of antibiotics are therefore closely monitored at all times. This review provides a current overview of the implications of strategies used by international governmental organisations, including the UN's 17 Sustainable Development Goals (SDGs), to address the problem of antibiotic resistance, as well as the "," a system incorporating a multidisciplinary effort to achieve the best possible health outcome by acknowledging the clear connections between humans, animals and their shared environment. The importance of public awareness and health literacy of lay audiences still needs to be further emphasised as part of global and local action plans. Antimicrobial resistance continues to be a major global public health dilemma of the 21st century. Already this topic is receiving substantial political input from the G7 countries and continues to be on the agenda of numerous political conferences. The consequences of failure to adequately address AMR are profound, with estimations of a return to the pre-antibiotic era, where everyday infections relating to childbirth, surgery and open fractured limbs could be potentially life-threatening. AMR itself represents a microcosm of factors, including social anthropology, civil unrest/war, diasporas, ethnic displacement, political systems, healthcare, economics, societal behaviour both at a population and individual level, health literacy, geoclimatic events, global travel and pharmaceutical innovation and investment, thus finding a solution that adequately addresses AMR and which helps stem further AMR emergence is complicated. Success will involve individuals, communities and nations all working together to ensure that the world continues to possess a sufficient armamentarium of effective antimicrobials that will sustain human and animal health, both now and in the future.
Topics: Animals; Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Anti-Infective Agents
PubMed: 37448857
DOI: 10.3389/bjbs.2023.11387 -
Journal of Infection and Public Health 2017Antimicrobial resistance in bacterial pathogens is a challenge that is associated with high morbidity and mortality. Multidrug resistance patterns in Gram-positive and... (Review)
Review
Antimicrobial resistance in bacterial pathogens is a challenge that is associated with high morbidity and mortality. Multidrug resistance patterns in Gram-positive and -negative bacteria are difficult to treat and may even be untreatable with conventional antibiotics. There is currently a shortage of effective therapies, lack of successful prevention measures, and only a few new antibiotics, which require development of novel treatment options and alternative antimicrobial therapies. Biofilms are involved in multidrug resistance and can present challenges for infection control. Virulence, Staphylococcus aureus, Clostridium difficile infection, vancomycin-resistant enterococci, and control in the Emergency Department are also discussed.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Humans
PubMed: 27616769
DOI: 10.1016/j.jiph.2016.08.007 -
Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects.Journal of Infection and Public Health Dec 2021Antibiotics have been used to cure bacterial infections for more than 70 years, and these low-molecular-weight bioactive agents have also been used for a variety of... (Review)
Review
Antibiotics have been used to cure bacterial infections for more than 70 years, and these low-molecular-weight bioactive agents have also been used for a variety of other medicinal applications. In the battle against microbes, antibiotics have certainly been a blessing to human civilization by saving millions of lives. Globally, infections caused by multidrug-resistant (MDR) bacteria are on the rise. Antibiotics are being used to combat diversified bacterial infections. Synthetic biology techniques, in combination with molecular, functional genomic, and metagenomic studies of bacteria, plants, and even marine invertebrates are aimed at unlocking the world's natural products faster than previous methods of antibiotic discovery. There are currently only few viable remedies, potential preventive techniques, and a limited number of antibiotics, thereby necessitating the discovery of innovative medicinal approaches and antimicrobial therapies. MDR is also facilitated by biofilms, which makes infection control more complex. In this review, we have spotlighted comprehensively various aspects of antibiotics viz. overview of antibiotics era, mode of actions of antibiotics, development and mechanisms of antibiotic resistance in bacteria, and future strategies to fight the emerging antimicrobial resistant threat.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Biofilms; Drug Resistance, Multiple, Bacterial; Humans
PubMed: 34756812
DOI: 10.1016/j.jiph.2021.10.020 -
European Journal of Pharmaceutical... Mar 2022Antibiotic resistance is a major health concern globally and has been estimated to cause 10 million deaths worldwide by year 2050 if the current trend of inappropriate... (Review)
Review
Antibiotic resistance is a major health concern globally and has been estimated to cause 10 million deaths worldwide by year 2050 if the current trend of inappropriate and excessive use of antibiotics continues. Although, the discovery of antibiotics has saved countless of lives for the past 80 years, increasing levels of bacterial resistance to antibiotics would jeopardize the progress in clinical and agricultural sectors and may cause life-threatening situations even for previously treatable bacterial infections. Antibiotic resistance would increase the levels of poverty of low-middle income countries mostly due to extended hospital stays, higher cost of treatment and untimely deaths that directly affect the total productivity rate. Recent incidences of antibiotic resistance have been gradually increasing globally and this may potentiate horizontal transmission of the resistant gene and have been linked with cross-resistance to other antibiotic families as well. This review summarizes the global burden of antibiotic resistance from the economic viewpoint, highlights the recent incidences of antibiotic resistance mainly related to Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella spp. and Staphylococcus aureus, describes the common mechanistic actions of antibiotic resistance and potential strategies to overcome antibiotic resistance.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Drug Resistance, Bacterial; Financial Stress; Humans; Prevalence
PubMed: 34936936
DOI: 10.1016/j.ejps.2021.106103 -
Trends in Biochemical Sciences Sep 2018Macrolide antibiotics inhibit protein synthesis by targeting the bacterial ribosome. They bind at the nascent peptide exit tunnel and partially occlude it. Thus,... (Review)
Review
Macrolide antibiotics inhibit protein synthesis by targeting the bacterial ribosome. They bind at the nascent peptide exit tunnel and partially occlude it. Thus, macrolides have been viewed as 'tunnel plugs' that stop the synthesis of every protein. More recent evidence, however, demonstrates that macrolides selectively inhibit the translation of a subset of cellular proteins, and that their action crucially depends on the nascent protein sequence and on the antibiotic structure. Therefore, macrolides emerge as modulators of translation rather than as global inhibitors of protein synthesis. The context-specific action of macrolides is the basis for regulating the expression of resistance genes. Understanding the details of the mechanism of macrolide action may inform rational design of new drugs and unveil important principles of translation regulation.
Topics: Anti-Bacterial Agents; Macrolides; Protein Biosynthesis
PubMed: 30054232
DOI: 10.1016/j.tibs.2018.06.011 -
MicrobiologyOpen Feb 2022It is well established that the gut microbiota plays an important role in host health and is perturbed by several factors including antibiotics. Antibiotic-induced... (Review)
Review
It is well established that the gut microbiota plays an important role in host health and is perturbed by several factors including antibiotics. Antibiotic-induced changes in microbial composition can have a negative impact on host health including reduced microbial diversity, changes in functional attributes of the microbiota, formation, and selection of antibiotic-resistant strains making hosts more susceptible to infection with pathogens such as Clostridioides difficile. Antibiotic resistance is a global crisis and the increased use of antibiotics over time warrants investigation into its effects on microbiota and health. In this review, we discuss the adverse effects of antibiotics on the gut microbiota and thus host health, and suggest alternative approaches to antibiotic use.
Topics: Adult; Animals; Anti-Bacterial Agents; Child; Female; Humans; Infant; Infant, Newborn; Microbiota; Pregnancy
PubMed: 35212478
DOI: 10.1002/mbo3.1260 -
MBio Dec 2021In the struggle with antibiotic resistance, we are losing. There is now a serious threat of moving into a postantibiotic world. High levels of resistance, in terms of... (Review)
Review
In the struggle with antibiotic resistance, we are losing. There is now a serious threat of moving into a postantibiotic world. High levels of resistance, in terms of both frequency and strength, have evolved against all clinically approved antibiotics worldwide. The usable life span of new clinically approved antibiotics is typically less than a decade before resistance reaches frequencies so high as to require only guarded usage. However, microbes have produced antibiotics for millennia without resistance becoming an existential issue. If resistance is the inevitable consequence of antibiotic usage, as has been the human experience, why has it not become an issue for microbes as well, especially since resistance genes are as prevalent in nature as the genes responsible for antibiotic production? Here, we ask how antibiotics can exist given the almost ubiquitous presence of resistance genes in the very microbes that have produced and used antibiotics since before humans walked the planet. We find that the context of both production and usage of antibiotics by microbes may be key to understanding how resistance is managed over time, with antibiotic synthesis and resistance existing in a paired relationship, much like a cipher and key, that impacts microbial community assembly. Finally, we put forward the cohesive, ecologically based "secret society" hypothesis to explain the longevity of antibiotics in nature.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Proteins; Drug Resistance, Bacterial; History, 20th Century; History, 21st Century; Humans
PubMed: 34872345
DOI: 10.1128/mBio.01966-21