Journal articles on the topic 'Microbial drug resistance'

To curtail pathogens or tumors, antimicrobial or antineoplastic drugs have been developed. These drugs target microbial/cancer growth and survival, thereby improving the host’s health. In attempts to evade the detrimental effects of such drugs, these cells have evolved several mechanisms over time. Some variants of the cells have developed resistances against multiple drugs or antimicrobial agents. Such microorganisms or cancer cells are said to exhibit multidrug resistance (MDR). The drug resistance status of a cell can be determined by analyzing several genotypic and phenotypic changes, which are brought about by significant physiological and biochemical alterations. Owing to their resilient nature, treatment and management of MDR cases in clinics is arduous and requires a meticulous approach. Currently, techniques such as plating and culturing, biopsy, gene sequencing, and magnetic resonance imaging are prevalent in clinical practices for determining drug resistance status. However, the major drawbacks of using these methods lie in their time-consuming nature and the problem of translating them into point-of-care or mass-detection tools. To overcome the shortcomings of conventional techniques, biosensors with a low detection limit have been engineered to provide quick and reliable results conveniently. These devices are highly versatile in terms of analyte range and quantities that can be detected to report drug resistance in a given sample. A brief introduction to MDR, along with a detailed insight into recent biosensor design trends and use for identifying multidrug-resistant microorganisms and tumors, is presented in this review.

Nowadays, infectious diseases caused by microorganisms are a major threat to human health, mostly because of drug resistance, multi-drug resistance and extensive-drug-resistance phenomena to microbial pathogens. During the last few years, obtaining hybrid azaheterocyclic drugs represents a powerful and attractive approach in modern antimicrobial therapy with very promising results including overcoming microbial drug resistance. The emphasis of this review is to notify the scientific community about the latest recent advances from the last five years in the field of hybrid azine derivatives with antimicrobial activity. The review is divided according to the main series of six-member ring azaheterocycles with one nitrogen atom and their fused analogs. In each case, the main essential data concerning synthesis and antimicrobial activity are presented.

Amino acids are ubiquitous vital biomolecules found in all kinds of living organisms including those in the microbial world. They are utilised as nutrients and control many biological functions in microorganisms such as cell division, cell wall formation, cell growth and metabolism, intermicrobial communication (quorum sensing), and microbial-host interactions. Amino acids in the form of enzymes also play a key role in enabling microbes to resist antimicrobial drugs. Antimicrobial resistance (AMR) and microbial biofilms are posing a great threat to the world’s human and animal population and are of prime concern to scientists and medical professionals. Although amino acids play an important role in the development of microbial resistance, they also offer a solution to the very same problem i.e., amino acids have been used to develop antimicrobial peptides as they are highly effective and less prone to microbial resistance. Other important applications of amino acids include their role as anti-biofilm agents, drug excipients, drug solubility enhancers, and drug adjuvants. This review aims to explore the emerging paradigm of amino acids as potential therapeutic moieties.

Currently, the efficacy of antibiotics is severely affected by the emergence of the antimicrobial resistance phenomenon, leading to increased morbidity and mortality worldwide. Multidrug-resistant pathogens are found not only in hospital settings, but also in the community, and are considered one of the biggest public health concerns. The main mechanisms by which bacteria develop resistance to antibiotics include changes in the drug target, prevention of entering the cell, elimination through efflux pumps or inactivation of drugs. A better understanding and prediction of resistance patterns of a pathogen will lead to a better selection of active antibiotics for the treatment of multidrug-resistant infections.

Quorum sensing is a cell-to-cell communication system that exists widely in the microbiome and is related to cell density. The high-density colony population can generate a sufficient number of small molecule signals, activate a variety of downstream cellular processes including virulence and drug resistance mechanisms, tolerate antibiotics, and harm the host. This article gives a general introduction to the current research status of microbial quorum-sensing systems, focuses on the role of quorum-sensing systems in regulating microbial resistance mechanisms, such as drug efflux pump and microbial biofilm formation regulation, and discusses a new strategy for the treatment of drug-resistant bacteria proposed by using quorum quenching to prevent microbial resistance.

OBJECTIVE: To investigate the perception of general dentists regarding the over-prescription of antibiotics leading to Antimicrobial drug resistance in their clinical practice. METHODOLOGY: A cross-sectional study encompassing a personalized Likert scale questionnaire on factors influencing anti-microbial resistance in dental general practices was conducted on 196 practitioners. The questionnaire inquired about different factors which tend to affect the over-prescription of antibiotics and influence anti-microbial resistance. It was piloted on 30 participants before dissemination. RESULTS: Factors showing the highest level of agreement were "lack of patient awareness regarding use of antibiotics" (96.9%), "over-the-counter availability" (95.4%), and self-medication" (95.4%). General dental practitioners were overprescribing in their clinical setup due to improper guidelines (24.4%), for their patient's satisfaction (21.2%), and lack of knowledge (19.2%).33.5% of them stated that patients reporting to them were self-medicating and 27.2% found that their patients had a lack of awareness. CONCLUSIONS: This study concluded that all the factors were responsible for the Antimicrobial Drug Resistance phenomenon in clinical dental practice. However, the majority of the dentists were over-prescribing antibiotics due to improper guidelines, lack of knowledge, and for the patient's satisfaction. KEYWORDS: Antimicrobial Drug Resistance; Awareness; Antibiotics; Dental General Practices; Over-the-Counter Drugs.

Hybrid molecule approach of drug design has become popular due to advantages such as delayed resistance, reduced toxicity, ease of treatment of co-infection and lower cost of preclinical evaluation. Antifungal drugs currently available for the treatment of fungal diseases suffer a major side effect of drug resistance. Hybrid drugs development is one of the approaches that has been employed to control microbial resistance. Their antifungal activity is influenced by their design. This review is focused on hybrid molecules exhibiting antifungal properties to guide scientists in search of more efficient drugs for the treatment of fungal diseases.

Antibiotics, both broad- and narrow spectrum, are widely used for treatment of specific infection by a consortium of microorganisms or by a single pathogen, respectively. Oral or intravenous, or even topical administration of different categories of antibiotics in various forms is a common practice round the globe. Yet for the recent years a major public health issue has been raised by the emergence of the drug-resistance microorganisms. A number of researches focused on the issue of the ineffectiveness of antibiotics as well as regarding the evolution of the drugresistance genes within the pathogenic microorganisms. Isolation of the drug-resistant microorganisms including the multi-drug resistant (MDR) and the extensively drug resistant (XDR) bacteria from a range of patients with microbiological infections has been seriously challenging the disease mitigation approaches. Besides, the dominance of the methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Staphylococcus aureus (VRSA), etc. are quite frequent as evident from different case studies. Current review focused on the origin and evolution of such drug-resistance incidences, and the promising remedies over the problems of drug-resistance. Bangladesh J Microbiol, Volume 36 Number 2 December 2019, pp 111-114

The three major groups of antifungal agents are there that are used in clinical use, azoles, polyenes, and allylamine/thiocarbamates, all own their antifungal activities to inhibit the reactivity of microbial or stop direct interaction of microbial with healthy cells.3 Microbial organometallic assimilation, the bioaccessibility, bioavailability, and bioaccumulation properties of inorganic metals in different antimicrobial moieties that are interrelated and classified as abiotic (e.g., organic carbon) and biotic (e.g., uptake and metabolism).4 IntroductionThe development of antifungal and antibacterial agents is different because of unpredictable consequences of the cellular events and features of the organisms. Hence, substantial attention has been focused on developing a more detailed understanding of the mechanisms of antimicrobial resistance, improved methods to detect resistance when it occurs search new antimicrobial options in treating infections caused by resistant organisms, and methods to prevent the emergence and spread of resistance in the first place since such efforts initiated.1 Most of the attention has devoted to the study of antibiotic resistance in bacteria for several reasons: (i) bacterial infections are responsible for the bulk of community-acquired and nosocomial infections; (ii) the large and expanding number of antibacterial classes offers a more diverse range of resistance mechanisms to study; and (iii) the ability to move bacterial resistance determinants into standard well-characterized bacterial strains facilitates the detailed study of molecular mechanisms of resistance in bacterial species.2 Moreover, the three major groups of antifungal agents are there that are used in clinical use, azoles, polyenes, and allylamine/thiocarbamates, all own their antifungal activities to inhibit the reactivity of microbial or stop direct interaction of microbial with healthy cells.3 Microbial organometallic assimilation, the bioaccessibility, bioavailability, and bioaccumulation properties of inorganic metals in different antimicrobial moieties that are interrelated and classified as abiotic (e.g., organic carbon) and biotic (e.g., uptake and metabolism).4 Modifying factors determine the amount of an inorganic metal that interacts at biological surfaces and binds it and finally was absorbed across the membranes.5 A major challenge is to consistently and accurately measure quantitative differences in bioavailability between multiple forms of inorganic metals in the environment. Microbes interact with metals and minerals in natural and synthetic environments, altering their physical and chemical state, with metals and minerals also able to affect microbial growth, activity, and survival. Additionally, many minerals are biogenic in origin, and the formation of such biominerals is of global geological and industrial significance, as well as provides important structural components for many organisms, including important microbial groups i.e. diatoms, foraminifera, and radiolarian. The current article summarizes each category of antimicrobial agents in order to illustrate the diverse modes of coordination/association of the ligands having different donor atoms (N. S. and O. etc.). This phenomenon is usually achieved by increasing asymmetry in the mode of coordination of these ligands as a donor of electrons. Wherever it was found appropriate, the comments relating to the physiological role, biochemical mechanism, environmental significance, and bioremediation potential of the microbial biotransformation are included (Fig. 1).6 Figure 1. During the following steps of metal usage, the acquired metal is transferred through intracellular trafficking pathways, which may include diverse storage compartments to be directed to cofactor assembly systems and final microorganism targeting can be achieved.7 Several of these used metals, organic moieties and related channeling routes, which have been described recently since their evolution, provide first insights into the later steps of metal assimilation and help in the characterization of an essential part of the cellular metal homeostasis network. Overall, so many challenges existed in this concept of antimicrobial drugs, and a few of them are related to the molecular entities of antimicrobial drugs. But, others have been concerned with the emergence of microbial resistance to the drugs applied and gradually limiting the efficiency of these antimicrobial remedies.8 But in the current, no solution is available, although the innovation of effective antimicrobial drugs is continuing. Several efforts have done for increasing the life of current drugs and designing of new antimicrobial drugs that will have to solve the problem of short life expectancy through scientific or adopting new strategies such as vaccination and other approaches for disease resistors are being tracked. The main causes of the resistance investigated and a few of them are as follows: innate features of the microbial, multiplying abilities of microbial, non-multiplying state, mutation, or gene transfer.9 In accordance with scientific evidence reported, it is easy to destroy the multiplying microbial quickly by existing antimicrobial drugs, but in the case of non-multiplying or slowly multiplying microbial, it is not quite easy. These findings elaborate on the need for highly effective antimicrobial drugs and conventional prolonged courses of drugs.10 One of the solutions that can be applied for it is; by applying the combination of antimicrobial drugs of both the categories, one class of drugs that target non-multiplying and other types of drugs that treat multiplying microbial.11 Sometimes these simple strategies can work and be an effective solution for the problem that can into existence because of the emergence of antimicrobial resistance.12 The other option is to develop a new class of antimicrobial agents that could remain effective for extended periods comparatively than presently existing antimicrobial drugs. The phenomenon of resistance especially emerged in the microbial impact and specific needs are there to deal it by applying antibacterial drugs and during treatment also, it can become a severe problem for the health of human beings. Therefore, the concern to have potential antimicrobial drugs is good whys and wherefores for it and is at the top of the current priority that is in demand. Antimicrobial drugs were developed by following a concept, which can induce new features to the organic moiety of the proposed drug to empower the central metal atom as well.13 Then, the developed antimicrobial drugs will have more potential to inhibit the multiplication processes of the microbial, and that is why it is considered a key concept in the discovery of antibacterial drugs. Among them, several other options are available that can be adopted for developing antimicrobial drugs, an alternative novel strategy is one of them.14 According to this concept, the primarily alleviate the current need, and after that incorporates new functional and many required features required for drug resistance, that are generated by interacting the potential moieties and effective metal combinations. These predetermined abilities were developed for targeting the non-multiplying latent.15 These strategies are helpful in the development of antimicrobial drugs that can prolong the duration of antimicrobial impact and enhanced the abilities that can break the microbialresistance. These routes of discovery are also helpful against prolonged suboptimal bactericidal growth, which is considered the main cause for the emergence of resistance.16 These settings of resistance and unhealthy biological features exist not only in the target pathogen, but also presented a different class of tissues and organs i.e. the gut, and throat. These pathogens can initiate fatal diseases in healthy tissues. The proper analysis of these strategies proved that long-term use of antimicrobial drugs can deal with microbial resistance in a better way comparatively than a shorter period. These results encourage researchers in dealing with the emergence of resistance initiated by the microbial.17 But, in some cases, the approach of a long course can develop more complications in the patients and as a result, it will enhance the power of resistance. In the current situation, the use of drug libraries can be applied to avoid such situations. Newly developed antimicrobial drugs should be screened against non-multiplying bacteria for the discovery of potential antimicrobial drugs that can destroy the microbial and originated resistance responsible for initiating the disease too. This opinion covers the approaches useful in the discovery of novel antimicrobial drugs by applying classic screening, by the analysis of structural changes done in drugs, by genome hunting; and by adopting a novel route that targets non-multiplying, latent microbial.18 The author tried his best to correlate all the original facts and concerning the chemistry of drug resistance with a special focus on antimicrobial drugs and concerned resistance mechanism underlying in the context of bioaccessibility, bioavailability, and bioaccumulation.19 In the end, it is a better way to adopt the latest scientific approach available, recently discovered tools and theories. By doing so, greater chances and much hope are there to be successful in the discovery of novel antimicrobial drugs that will reduce the emergence of resistance caused by the antimicrobial agents and treat the diseases in a better way. References: Ghannoum, M. A.; Rice, L. B. Antifungal agents: Mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clinical Microbiology Reviews. 1999, 12, 501–517. Miotto, P.; Zhang, Y.; Cirillo, D. M.; Yam, W. C. Drug resistance mechanisms and drug susceptibility testing for tuberculosis. Respirology. 2018, 23, 1098–1113. Weersma, R. K.; Zhernakova, A.; Fu, J. Interaction between drugs and the gut microbiome. 2020, 69, 1510–1519. Kumar, R.; Chhikara, B. S. Organometallic assemblies: π-electron delocalization, μ-bridging spacers, flexibility, lipophilic nature, bio-accessibility, bioavailability, intracellular trafficking pathways and antimicrobial assimilation. Organomet. Chem. 2015, 776. McGeer, J.; et al. Issue paper on the bioavailability and bioaccumulation of metals. in US Environmental Protection Agency risk assessment forum. 2004, 1200, 122. Orazi, G.; O’Toole, G. A. ‘It takes a village’: Mechanisms underlying antimicrobial recalcitrance of polymicrobial biofilms. Journal of Bacteriology. 2020, 202. Claudel, M.; Schwarte, J. V.; Fromm, K. M. New Antimicrobial Strategies Based on Metal Complexes. Chemistry (Easton). 2020, 2, 849–899. Cascioferro, S.; et al. Thiazoles, Their Benzofused Systems, and Thiazolidinone Derivatives: Versatile and Promising Tools to Comb at Antibiotic Resistance. Journal of Medicinal Chemistry. 2020, 63, 7923–7956. Tyson, G. H.; Sabo, J. L.; Rice-Trujillo, C.; Hernandez, J.; McDermott, P. F. Whole-genome sequencing based characterization of antimicrobial resistance in Enterococcus. Pathog. Dis. 2018, 76. Yoo, H. H.; Kim, I. S.; Yoo, D. H.; Kim, D. H. Effects of orally administered antibiotics on the bioavailability of amlodipine: Gut microbiota-mediated drug interaction. Hypertens. 2016, 34, 156–162. Du, D.; et al. Multidrug efflux pumps: structure, function and regulation. Nature Reviews Microbiology. 2018, 6, 523–539. Luthra, S.; Rominski, A.; Sander, P. The role of antibiotic-target-modifying and antibiotic-modifying enzymes in mycobacterium abscessusdrug resistance. Frontiers in Microbiology. 2018, 9. Abd-El-Aziz, A. S.; Abdelghani, A. A.; Mishra, A. K. Optical and Biological Properties of Metal-Containing Macromolecules. Journal of Inorganic and Organometallic Polymers and Materials. 2020, 30, 3–41. Alamino, R. C. An agent-based lattice model for the emergence of anti-microbial resistance. Theor. Biol. 2020, 486. Serban, G.; Stanasel, O.; Serban, E.; Bota, S. 2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents. Drug Design, Development and Therapy. 2018, 12, 1545–1566. Levy, S. B.; Bonnie, M. Antibacterial resistance worldwide: Causes, challenges and responses. Nature Medicine. 2004, 10, S122–S129. Kumar S.; S. B. R. An Overview of Mechanisms and Emergence of Antimicrobials Drug Resistance. Anim. Vet. Sci. 2013, 1, 7 –14. Fairlamb, A. H.; Gow, N. A. R.; Matthews, K. R.; Waters, A. P. Drug resistance in eukaryotic microorganisms. Nature Microbiology. 2016, 1. Rhouma, M.; Beaudry, F.; Thériault, W.; Letellier, A. Colistin in pig production: Chemistry, mechanism of antibacterial action, microbial resistance emergence, and one health perspectives. Frontiers in Microbiology. 2016, 7.

With the escalating global antimicrobial resistance crisis, there is an urgent need for innovative strategies against drug-resistant microbes. Accumulating evidence indicates microbial extracellular vesicles (EVs) contribute to antimicrobial resistance. Therefore, comprehensively elucidating the roles and mechanisms of microbial EVs in conferring resistance could provide new perspectives and avenues for novel antimicrobial approaches. In this review, we systematically examine current research on antimicrobial resistance involving bacterial, fungal, and parasitic EVs, delineating the mechanisms whereby microbial EVs promote resistance. Finally, we discuss the application of bacterial EVs in antimicrobial therapy.

Antimicrobial resistance and tolerance are natural phenomena that arose due to evolutionary adaptation of microorganisms against various xenobiotic agents. These adaptation mechanisms make the current treatment options challenging as it is increasingly difficult to treat a broad range of infections, associated biofilm formation, intracellular and host adapted microbes, as well as persister cells and microbes in protected niches. Therefore, novel strategies are needed to identify the most promising drug targets to overcome the existing hurdles in the treatment of infectious diseases. Furthermore, discovery of novel drug candidates is also much needed, as few novel antimicrobial drugs have been introduced in the last two decades. In this review, we focus on the strategies that may help in the development of innovative small molecules which can interfere with microbial resistance mechanisms. We also highlight the recent advances in optimization of growth media which mimic host conditions and genome scale molecular analyses of microbial response against antimicrobial agents. Furthermore, we discuss the identification of antibiofilm molecules and their mechanisms of action in the light of the distinct physiology and metabolism of biofilm cells. This review thus provides the most recent advances in host mimicking growth media for effective drug discovery and development of antimicrobial and antibiofilm agents.

SUMMARYThe rise of antimicrobial resistance, coupled with a lack of industrial focus on antimicrobial discovery over preceding decades, has brought the world to a crisis point. With both human and animal health set to decline due to increased disease burdens caused by near untreatable microbial pathogens, there is an urgent need to identify new antimicrobials. Central to this is the elucidation of new, robustly validated, drug targets. Informed by industrial practice and concerns, the use of both biological and chemical tools in validation is key. In parallel, repurposing approved drugs for use as antimicrobials may provide both new treatments and identify new targets, whilst improved understanding of pharmacology will help develop and progress good ‘hits’ with the required rapidity. In recognition of the need to increase research efforts in these areas, in 14–16 September 2017, the British Society for Parasitology (BSP) Autumn Symposium was hosted at Durham University with the title: Microbial Protein Targets: towards understanding and intervention. Staged in collaboration with the Royal Society of Chemistry (RSC) Chemistry Biology Interface Division (CBID), the core aim was to bring together leading researchers working across disciplines to imagine novel approaches towards combating infection and antimicrobial resistance. Sessions were held on: ‘Anti-infective discovery, an overview’; ‘Omic approaches to target validation’; ‘Genetic approaches to target validation’; ‘Drug target structure and drug discovery’; ‘Fragment-based approaches to drug discovery’; and ‘Chemical approaches to target validation’. Here, we introduce a series of review and primary research articles from selected contributors to the Symposium, giving an overview of progress in understanding antimicrobial targets and developing new drugs. The Symposium was organized by Paul Denny (Durham) for the BSP and Patrick Steel (Durham) for RSC CBID.

In the present research, the steroidal anti-asthmatic drug beclomethasone dipropionate was subjected to microbial biotransformation by Aspergillus niger. Beclomethasone dipropionate was transformed into various metabolites first time from microbial transformation. New drug metabolites produced can act as new potential drug molecules and can replace the old drugs in terms of safety, efficacy, and least resistance. They were purified by preparative thin layer chromatography technique, and their structures were elucidated using modern spectroscopic techniques, such as 13C NMR, 1H NMR, HMQC, HMQC, COSY, and NOESY, and mass spectrometry, such as EI-MS. Four metabolites were purified: (i) beclomethasone 17-monopropionate, (ii) beclomethasone 21-monopropionate, (iii) beclomethasone, and (iv) 9beta,11beta-epoxy-17,21-dihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 21-propionate.

SUMMARYThe availability of genome sequence data has facilitated the development of high-throughput genetic screening approaches in microbial pathogens. In the African trypanosome, Trypanosoma brucei, genome-scale RNA interference screens have proven particularly effective in this regard. These genetic screens allow for identification of the genes that contribute to a particular pathway or mechanisms of interest. The approach has been used to assess loss-of-fitness, revealing the genes and proteins required for parasite viability and growth. The outputs from these screens predict essential and dispensable genes and facilitate drug target prioritization efforts. The approach has also been used to assess resistance to anti-trypanosomal drugs, revealing the genes and proteins that facilitate drug uptake and action. These outputs also highlight likely mechanisms underlying clinically relevant drug resistance. I first review these findings in the context of what we know about current drugs. I then describe potential contributions that these high-throughput approaches could make to the development and implementation of new drugs.

AbstractHigh levels of antimicrobial drug resistance deleteriously affecting the outcome of treatment with antibacterial agents are causing increasing concern worldwide. This is particularly worrying in patients with cirrhosis with a depressed immune system and heightened susceptibility to infection. Antibiotics have to be started early before results of microbiological culture are available. Current guidelines for the empirical choice of antibiotics in this situation are not very helpful, and embracing antimicrobial stewardship including rapid de-escalation of therapy are not sufficiently emphasised. Multi-drug resistant organism rates to quinolone drugs of up to 40% are recorded in patients with spontaneous bacterial peritonitis on prophylactic antibiotics, leading to a break-through recurrence of intra-peritoneal infection. Also considered in this review is the value of rifaximin-α, non-selective beta-blockers, and concerns around proton pump inhibitor drug use. Fecal microbial transplantation and other gut-targeting therapies in lessening gut bacterial translocation are a promising approach, and new molecular techniques for determining bacterial sensitivity will allow more specific targeted therapy.

Dear Reader, Many of you would have noted the announcement of the establishment of a Centre by ICMR in New Delhi, in collaboration with a multinational pharmaceutical corporation to combat anti-microbial resistance (AMR). We see large full page advertisements with the words “AMR” in the front page of the daily news papers. These advertisements are the result of the efforts to draw the attention of all to the development of Anti-microbial resistance at a much faster pace than predicted. The action is noteworthy. However, it is difficult to comprehend how these advertisements will help to reduce AMR. While many more activities are being planned, it is hoped that the holistic approach being pursued will involve many more institutions and organizations. CDSCO has notified a separate schedule of drugs, Schedule H1 consisting of antibiotics, to ensure better prescription practices by medical professionals and the requirement that retailers maintain copies of the prescriptions served

The ability of microorganisms to form multicellular three-dimensional associates (biofilms) increases significantly their resistance to the influence of negative environmental factors. One of the manifestations of this ability is the development of drug resistance, which leads to a decrease in the effectiveness of drugs and significantly complicates the treatment of the corresponding diseases. Despite the unabated interest in this extremely undesirable phenomenon, there is no generally accepted explanation of the mechanisms of resistance development. At the same time, the generalization of data on the properties of biofilms allows us to get closer to the understanding of this process, but also to substantiate the proposition about its negative impact on adjacent tissues.

Plasmodium parasites, the causative agent of malaria infections, rapidly evolve drug resistance and escape detection by the human immune response via the incredible mutability of its genome. Understanding the genetic mechanisms by which Plasmodium parasites develop antimalarial resistance is essential to understanding why most drugs fail in the clinic and designing the next generation of therapies. A systematic genomic analysis of 262 Plasmodium falciparum clones with stable in vitro resistance to 37 diverse compounds with potent antimalarial activity was undertaken with the main goal of identifying new drug targets. Despite several challenges inherent to this method of in vitro drug resistance generation followed by whole genome sequencing, the study was able to identify a likely drug target or resistance gene for every compound for which resistant parasites could be generated. Known and novel P falciparum resistance mediators were discovered along with several new promising antimalarial drug targets. Surprisingly, gene amplification events contributed to one-third of the drug resistance acquisition events. The study can serve as a model for drug discovery and resistance analyses in other similar microbial pathogens amenable to in vitro culture.

Antimicrobial drugs have made outstanding contributions to the treatment of pathogenic infections. However, the emergence of drug resistance continues to be a major threat to human health in recent years, and therefore, the search for novel antimicrobial drugs is particularly urgent. With a deeper understanding of microbial habits and drug resistance mechanisms, various creative strategies for the development of novel antibiotics have been proposed. Stilbenoids, characterized by a C6–C2–C6 carbon skeleton, have recently been widely recognized for their flexible antimicrobial roles. Here, we comprehensively summarize the mode of action of stilbenoids from the viewpoint of their direct antimicrobial properties, antibiofilm and antivirulence activities and their role in reversing drug resistance. This review will provide an important reference for the future development and research into the mechanisms of stilbenoids as antimicrobial agents.

The microbial cell wall plays a crucial role in biofilm formation and drug resistance.cspAencodes a repeat-rich glycophosphatidylinositol-anchored cell wall protein in the pathogenic fungusAspergillus fumigatus. To determine whethercspAhas a significant impact on biofilm development and sensitivity to antifungal drugs inA. fumigatus, a ΔcspAmutant was constructed by targeted gene disruption, and we then reconstituted the mutant to wild type by homologous recombination of a functionalcspAgene. Deletion ofcspAresulted in a rougher conidial surface, reduced biofilm formation, decreased resistance to antifungal agents, and increased internalization by A549 human lung epithelial cells, suggesting thatcspAnot only participates in maintaining the integrity of the cell wall, but also affects biofilm establishment, drug response, and invasiveness ofA. fumigatus.

Background: Bloodstream infection (BSI) is frequent in stroke, with poorer outcomes when microbial isolates are multi-drug resistant. There is a shortage of published data on BSI amongst stroke patients in Nigeria. Objective: To describe the microbial isolates and the antimicrobial resistance pattern among microbial isolates in BSI in stroke patients. Methods: This retrospective study of all hospitalized stroke patients with BSI at the University of Benin Teaching Hospital, Benin City, Nigeria covered July 2018 to June 2022. The demographics, stroke type, microbial isolates and antimicrobial resistance patterns were studied. Results: Blood culture studies were conducted among 834 stroke patients with infections; 410 (49.2%) had positive growth for microbial organisms. Amongst those with positive blood cultures, 53% (217/410) were females, while 56% had a haemorrhagic stroke. The mean age was 76.9±13.9 years, with about 80% of them aged ≥ 65. Infections of the respiratory tract (45%) and the urinary tract (33%) were the possible primary sources of BSI. The leading isolates included Enterococcus faecalis (18.5%), Klebsiella oxotyca (12.9%), Proteus mirabilis (12.9%), Staphylococcus aureus (11.5%), and Escherichia coli (11.2%). Approximately 88% of the isolates were multi-drug resistant, with 100% resistance to cefuroxime, ceftazidime, and co-trimoxazole, 83.3% to erythromycin and 75% resistance to ampicillin. The elderly patients were significantly more likely to acquire multi-drug resistant micro-organisms (p = 0.007). Conclusion: Stroke patients, especially the older ones, are susceptible to bloodstream infection from multi-drug-resistant micro-organisms, contributing to increased morbidity and mortality among stroke patients.

Trillions of diverse microbes reside in the gut and are deeply interwoven with the human physiological process, from food digestion, immune system maturation, and fighting invading pathogens, to drug metabolism. Microbial drug metabolism has a profound impact on drug absorption, bioavailability, stability, efficacy, and toxicity. However, our knowledge of specific gut microbial strains, and their genes that encode enzymes involved in the metabolism, is limited. The microbiome encodes over 3 million unique genes contributing to a huge enzymatic capacity, vastly expanding the traditional drug metabolic reactions that occur in the liver, manipulating their pharmacological effect, and, ultimately, leading to variation in drug response. For example, the microbial deactivation of anticancer drugs such as gemcitabine can lead to resistance to chemotherapeutics or the crucial role of microbes in modulating the efficacy of the anticancer drug, cyclophosphamide. On the other hand, recent findings show that many drugs can shape the composition, function, and gene expression of the gut microbial community, making it harder to predict the outcome of drug-microbiota interactions. In this review, we discuss the recent understanding of the multidirectional interaction between the host, oral medications, and gut microbiota, using traditional and machine-learning approaches. We analyze gaps, challenges, and future promises of personalized medicine that consider gut microbes as a crucial player in drug metabolism. This consideration will enable the development of personalized therapeutic regimes with an improved outcome, ultimately leading to precision medicine.

Antibiotic resistance has become a threat to microbial therapies nowadays. The conventional approaches possess several limitations to combat microbial infections. Therefore, to overcome such complications, novel drug delivery systems have gained pharmaceutical scientists’ interest. Significant findings have validated the effectiveness of novel drug delivery systems such as polymeric nanoparticles, liposomes, metallic nanoparticles, dendrimers, and lipid-based nanoparticles against severe microbial infections and combating antimicrobial resistance. This review article comprises the specific mechanism of antibiotic resistance development in bacteria. In addition, the manuscript incorporated the advanced nanotechnological approaches with their mechanisms, including interaction with the bacterial cell wall, inhibition of biofilm formations, activation of innate and adaptive host immune response, generation of reactive oxygen species, and induction of intracellular effect to fight against antibiotic resistance. A section of this article demonstrated the findings related to the development of delivery systems. Lastly, the role of microfluidics in fighting antimicrobial resistance has been discussed. Overall, this review article is an amalgamation of various strategies to study the role of novel approaches and their mechanism to fight against the resistance developed to the antimicrobial therapies.

The biggest challenge in the present-day healthcare scenario is the rapid emergence and spread of antimicrobial resistance due to the rampant use of antibiotics in daily therapeutics. Such drug resistance is associated with the enhancement of microbial virulence and the acquisition of the ability to evade the host’s immune response under the shelter of a biofilm. Quorum sensing (QS) is the mechanism by which the microbial colonies in a biofilm modulate and intercept communication without direct interaction. Hence, the eradication of biofilms through hindering this communication will lead to the successful management of drug resistance and may be a novel target for antimicrobial chemotherapy. Chitosan shows microbicidal activities by acting electrostatically with its positively charged amino groups, which interact with anionic moieties on microbial species, causing enhanced membrane permeability and eventual cell death. Therefore, nanoparticles (NPs) prepared with chitosan possess a positive surface charge and mucoadhesive properties that can adhere to microbial mucus membranes and release their drug load in a constant release manner. As the success in therapeutics depends on the targeted delivery of drugs, chitosan nanomaterial, which displays low toxicity, can be safely used for eradicating a biofilm through attenuating the quorum sensing (QS). Since the anti-biofilm potential of chitosan and its nano-derivatives are reported for various microorganisms, these can be used as attractive tools for combating chronic infections and for the preparation of functionalized nanomaterials for different medical devices, such as orthodontic appliances. This mini-review focuses on the mechanism of the downregulation of quorum sensing using functionalized chitosan nanomaterials and the future prospects of its applications.

Antimicrobial resistance is a global public health issue and one of the most serious threats to the mankind today. Some bacterial strains have acquired resistance to most antimicrobial drugs and, therefore, new antibacterial agents that would overcome resistant strains are needed. In 2017, the World Health Organization published a list of priority antimicrobial-resistant pathogens. Most of these agents are gram-negative bacteria. Due to their structure, the gram-negative bacteria are more resistant to antimicrobials than gram-positive bacteria and cause significant morbidity and mortality worldwide. The main resistance mechanisms are: restricted drug absorption, modification of the target attack, inactivation of the antimicrobial drug by production of hydrolyzing enzymes and active drug efflux. These mechanisms may be innate or acquired by microorganisms, and understanding those mechanisms may create new treatment options for infectious pathology and may contribute to the development of new antimicrobial drugs that counter the microbial attempts to become resistant.

With the ever-increasing population and improvement in the healthcare system in the 21st century, the incidence of chronic microbial infections and associated health disorders has also increased at a striking pace. The ability of pathogenic microorganisms to form biofilm matrix aggravates the situation due to antibiotic resistance phenomenon resulting in resistance against conventional antibiotic therapy which has become a public health concern. The canonical Quorum Sensing (QS) signaling system hierarchically regulates the expression of an array of virulence phenotypes and controls the development of biofilm dynamics. It is imperative to develop an alternative, yet effective and non-conventional therapeutic approach, popularly known as “anti-infective therapy” which seems to be interesting. In this regard, targeting microbial QS associated virulence and biofilm development proves to be a quite astonishing approach in counteracting the paucity of traditional antibiotics. A number of synthetic and natural compounds are exploited for their efficacy in combating QS associated microbial infections but the bioavailability and biocompatibility limit their widespread applications. In this context, the nanotechnological intervention offers a new paradigm for widespread biomedical applications starting from targeted drug delivery to diagnostics for the diagnosis and treatment of infectious diseases, particularly to fight against microbial infections and antibiotics resistance in biofilms. A wide range of nanomaterials ranging from metallic nanoparticles to polymeric nanoparticles and recent advances in the development of carbon-based nanomaterials such as Carbon Nanotubes (CNTs), Graphene Oxide (GO) also immensely exhibited intrinsic antiinfective properties when targeted towards microbial infections and associated MDR phenomenon. In addition, the use of nano-based platforms as carriers emphatically increases the efficacy of targeted and sitespecific delivery of potential drug candidates for preventing microbial infections.

Microbiological risk assessments generally focus on estimating adverse human health risks from exposures to human pathogenic microbes. The assessment of potential human health risks posed by pathogens that have acquired resistance to antimicrobial drugs is a new application of risk assessment that is closely related to microbiological risk assessment. Antimicrobial resistance risk assessment is a risk analytical process that focuses on resistance determinants as hazardous agents that might lead to drug-resistant microbial infections in humans exposed to bacteria carrying the determinants. Antimicrobial-resistant infections could occur directly from actively invading or opportunistic pathogens or indirectly from the transfer of resistance genes to other bacteria. Here, we discuss risk assessment models that might be employed to estimate risks from drug-resistant bacteria in the animal food pathway and the types of models and data that may be used for microbiological risk assessments or antimicrobial resistance risk assessments.