Antibiotic Resistance Crisis Research Articles

Synthesis, In Silico Designing, Microbiological Evaluation and Structure Activity Relationship of Novel Amide Derivatives of 1-(2,4-Dinitrophenyl)-2-(3-Methylbenzo[b]Thiophen-6-yl)-1H-Benzo[d]Imidazole-5-Carboxylic Acid

Background Due to the growing crisis of antibiotic resistance, ample of different antibiotics accessible is declining and there are only a few of new antibiotics in the drug discovery pipeline. Therefore, there is an imperative need for the progress of new antimicrobial drugs. Method In the present study, synthesized amide derivatives of 1-(2,4-dinitrophenyl)-2-(3-methylbenzo[b]thiophen-6-yl)-1H-benzo[d]imidazole-5-carboxylic acid by centralize the tyrosyl-tRNA synthetase and aminoacyl-tRNA synthetase (AaRS)enzymes and inhibition study by docking leads to antimicrobial activity. Molecular docking studies were conceded out on a designed amide library, and the best 23 focused amide compounds of 1-(2,4-dinitrophenyl)-2-(3-methylbenzo[b]thiophen-6-yl)-1H-benzo[d]imidazole-5-carboxylic acid were privileged for synthesis based on the dock score evaluated by Schrodinger’s maestro package and AutoDock Vina 4.2 docking software against crystal structure of enzymes (PDB ID: 1wny.PDBQT and1jil.PDBQT) and investigated for in vitro antimicrobial activity. Results Among the library, the best compound A-4, A-5 and A-23 showing excellent dock score by AutoDock Vina/Schrodinger’s maestro against 1wny.PDBQT:1jil.PDBQT is −9.2:–10.6/–5.402: –5.653, −9.2: –10.6/–5.526/–5.734, −9.2: –10.6/–5.183: −5.679 as compared to standard drug dock score −10.2: –10.6/–5.847: –5.895 Derivatives A-4, A-5 and A-23 also flourished good MIC against six representative microorganisms as compared to standard by tube dilution method. Conclusions In vitro outcome naked that new synthesized compounds having excellent antimicrobial activity can be accustomed for in vivo studies for future.

153. pilot Study of a Novel Whole-genome Sequencing Based Rapid Bacterial Identification Assay in Patients with Bacteremia

BackgroundBlood stream infections (BSI) are among the leading cause of morbidity and mortality, yet gold standard culture-based diagnostics have limited ability to guide therapeutic intervention due to multi-day turnaround time and low sensitivity. Day Zero Diagnostics has developed Blood2Bac™, a culture-free, species agnostic process to enrich bacteria direct from whole blood. Coupled with whole genome sequencing (WGS) and Day Zero Diagnostics’ Keynome® algorithmic tools for species ID and antimicrobial resistance (AMR), we conducted the first proof-of-concept feasibility study in an inpatient clinical setting.MethodsStudy participants were enrolled and specimens collected from Boston Medical Center. Eligibility criteria included hospitalized adults with suspected and/or documented BSI, irrespective of empiric antibiotic therapy duration. Whole blood samples were processed with Blood2Bac, sequenced on a nanopore platform, and bacterial ID determined with Keynome ID. Keynome ID results were compared with blood culture results to measure concordance.ResultsSpecimens from 21 participants were processed with Blood2Bac and nanopore sequencing. For 20/21 samples, Keynome ID calls were concordant with clinical blood culture, where 6 concordant positive and 14 were concordant negative. In 3 concordant samples, Keynome ID called positive while concurrent blood cultures were negative. However, all IDs corresponded with positive blood culture results from the day prior, suggesting potentially higher sensitivity for the Blood2Bac compared to blood culture. Two concordant positive IDs, resulted in >95% of the genome recovered and Keynome concomitantly resulted in AMR predictions with 100% accuracy compared to pathogen phenotype. In 1 discordant specimen, the Keynome ID result was negative while blood cultures 8 hours before were positive. In this case, the patient was on empiric therapy for 8 days prior to samples collection and cultures were negative 19-hours post specimen collection.ConclusionThese results highlight the sensitivity of a real-time blood WGS approach to identify BSI and its utility as a diagnostic to minimize unnecessary antibiotic exposure contributing to the antibiotic resistance crisis.Disclosures Archana Asundi, MD, Gilead (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator)ViiV (Scientific Research Study Investigator) Nicole Billings, PhD, Day Zero Diagnostics (Employee) Zoe H. Rogers, MPH, Day Zero Diagnostics (Employee, Shareholder) Lisa S. Cunden, PhD, Day Zero Diagnostics (Shareholder) Imaly A. Nanayakkara, PhD, Day Zero Diagnostics (Employee, Shareholder) Chiahao Tsui, n/a, Day Zero Diagnostics (Employee, Shareholder) Paul Knysh, PhD, Day Zero Diagnostics (Employee) Cabell Maddux, n/a, Day Zero Diagnostics (Employee, Shareholder) Zachary Munro, n/a, Day Zero Diagnostics Inc. (Employee, Shareholder) Ian Herriott, BS, Day Zero Diagnostics (Employee, Shareholder) Miriam Huntley, PhD, Day Zero Diagnostics (Employee, Shareholder) Nina H. Lin, MD, Gilead Sciences (Scientific Research Study Investigator)ViiV (Scientific Research Study Investigator)

1218. Comparing the Diagnostic Accuracy of Clinician Judgement to a Novel Host Response Diagnostic for Acute Respiratory Illness

BackgroundDiscriminating bacterial and viral infections remains clinically challenging. The resulting antibacterial misuse contributes to antimicrobial resistance. Host gene expression-based tests are a promising strategy to discriminate of bacterial and viral infections, but their potential clinical utility has not yet been evaluated.MethodsA host gene expression biosignature was measured using either qRT-PCR or microarray in 683 ED subjects with suspected infection. Based on chart reviews, we recorded clinical diagnosis as defined both by the provider assessment and by the provider treatment plan. The biosignature, diagnosis, treatment plan, and procalcitonin were compared to clinical adjudication as the reference standard. With this as a baseline, we then calculated average weighted accuracy (AWA) and change in overall net benefit (∆NB), weighting bacterial false negatives four times more seriously than false positives.ResultsGene expression correctly classified the three possible disease etiologies (bacterial, viral, or non-infectious) 76.1% of the time, outperforming provider diagnosis, provider treatment, and procalcitonin (Table 1). Overall accuracy was higher in subjects with bacterial infections (n=278, 83.8% accurate) compared to those with viral (n=234, 76.5%) and non-infectious (n=171, 63.2%) etiologies. Due to a strong sensitivity bias to treat bacterial infections at the expense of diagnostic accuracy and specificity, the provider diagnosis was overall more accurate than the corresponding treatment plan (71.4% accuracy vs. 68.1%), resulting in inappropriate antibiotic use in 41.0% of cases where antibiotics were prescribed. The gene expression test had significantly higher AWA for the diagnosis of bacterial infection than both procalcitonin and provider treatment (82.4% vs. 70.3% and 74.4%, respectively; p < 0.0001). Consequently, the host gene expression test had greater net benefit than provider treatment (∆NBbact = 9.9%), provider diagnosis (∆NBbact = 4.4%), and procalcitonin (∆NBbact = 27.1%).Table 1: Summary of provider, procalcitonin, and host gene expression test performance in a cohort of 683 subjects. ConclusionHost gene expression-based tests to distinguish bacterial and viral infection can facilitate more appropriate treatment, leading to improved patient outcomes and mitigating the antibiotic resistance crisis.Disclosures Geoffrey S. Ginsburg, MD PhD, Predigen, Inc (Shareholder, Other Financial or Material Support) Ephraim L. Tsalik, MD, MHS, PhD, Predigen (Shareholder, Other Financial or Material Support, Founder)

The Antibiotic Resistance Crisis - An Indian Perspective

This research study reiterates the optimal usage of antimicrobial medicines in humans and animals to lessen antibiotic resistance. A primary survey was conducted to study an individual’s role in prevention and control of antibiotic resistance. It was found that antibiotics are being irrationally used and the efficacy of antibiotics, as previously transforming the medical sciences and saving lives of many is in danger due to the quick emergence of bacterial resistance. Extensive efforts are therefore required to manage crisis by implementing new policies and renewing research efforts. Additionally, there exists a dire need to educate patients and public regarding antibiotic resistance crisis.

Modern Problems of Antibiotic Therapy in Ophthalmology and the Perspective Ways of Solution. Literature Review

To date, the problem of interaction between humans and the surrounding microbiome continues to grow in the human population, which is expressed in the so-called crisis of antibiotic resistance. Microorganisms, being pathogens of infectious diseases, no longer have guaranteed pharmacological barriers that can stop their reproduction, which means that they continue to claim thousands of lives every year. This phenomenon is associated with many reasons, such as the presence of mobile genetic elements in bacteria that perform the function of horizontal gene transfer, responsible for their resistance to antibiotics. Mutational microevolution changes in the genotype of a bacterial cell can lead to the development of uncontrolled polyresistance. Also, the combination of micro-and macroevolutionary changes in the external signs of the pathogen determines the system of factors of aggression, invasion, protection and adaptation. Other factors causing antibioticoresistance include overuse of antibiotics and self-nominations during periods of self-medication, antibiotics and medical staff in subclinical doses, too short treatment courses, and sometimes their function in the absence of indications for therapy, the extensive use of antibiotics in agriculture. A number of preventive measures that could significantly affect the crisis of antibiotic resistance are being actively worked out at the state level and include programs to reduce the free circulation of antibiotics, optimize therapeutic regimes, improve diagnostic measures for the verification of pathogens, prevent the spread of infections, optimize interaction between pharmaceutical companies and registration organizations, stimulate investment and public-private partnership, and of course the international initiative on systemic interaction. This paper examines the cause-and-effect relationships that can have a direct impact on the resolution of the crisis of antibiotic resistance, which can be traced in the historical context and up to the present time, as well as describes modern promising scientific and technical directions that can give humanity a new «Golden bullet» against pathogens, in particular the use of artificial fluorophores-quantum dots.

A High-Throughput Method for Screening for Genes Controlling Bacterial Conjugation of Antibiotic Resistance.

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

Pseudomonas aeruginosa at the dawn of a post-antibiotic era: clinical significance, resistance mechanisms, novel antibiotics and alternative treatments

Since their discovery, antibiotics have helped treat diseases prior to which many were untreatable, saving millions of lives. However, due to the overuse of antibiotics in medicine and agriculture, the advent of resistant strains of bacteria followed shortly after. The current antibiotic resistance crisis is bringing humanity closer to a post-antibiotic era, when all the advancements made by modern medicine could easily be reversed. Pseudomonas aeruginosa is a Gram-negative, rod-shaped bacterium, ubiquitous owing to its minimal nutritional and growth requirements. P. aeruginosa is one of the pathogens included in the priority list of the WHO, being assessed as critical due to its high antimicrobial resistance, leaving only a few effective treatment options to combat it. As an opportunistic pathogen, P. aeruginosa establishes infection in immunocompromised patients, primarily in hospital settings. In order to initiate infection, it requires several virulence factors that mediate the invasion of the pathogen into host cells. Owing to the multiple resistance mechanisms of P. aeruginosa, it has developed resistance to most classes of antibiotics. Due to its increased resistance, treating P. aeruginosa infections is a great challenge for clinicians. Several β-lactam/β-lactamase combinations have been approved and are available as treatment options, which overall show high efficacy against P. aeruginosa. Moreover, novel antibiotics are currently in development as possible antipseudomonal agents, including a Pseudomonas-specific formulation. In addition, new strategies such as bacteriophage therapy, pyocins or the inhibition of the quorum sensing system are being investigated for the treatment of P. aeruginosa infections.

Monoclonal Antibody-Based Biosensor for Point-of-Care Detection of Type III Secretion System Expressing Pathogens.

It is predicted that the antibiotic resistance crisis will result in an annual death rate of 10 million people by the year 2050. To grapple with the challenges of the impending crisis, there is an urgent need for novel and rapid diagnostic tools. In this study, we developed a novel monoclonal antibody-named mAb-EspB-B7-that targets the EspB protein, a component within the bacterial type 3 secretion system (T3SS), which is mainly expressed in Gram-negative pathogens and is essential for bacterial infectivity. We found that mAb-EspB-B7 has high affinity and specificity toward recombinant and native EspB proteins; is stable over a range of pH levels, temperatures, and salt concentrations; and retains its functionality in human serum. We identified the epitope for mAb-EspB-B7 and validated it by competitive enzyme-linked immunosorbent assay (ELISA). Since this epitope is conserved across several T3SS-harboring pathogens, mAb-EspB-B7 holds great potential for development as an active component in precise and rapid diagnostic tools that can differentiate between commensal and pathogenic bacterial strains. To this end, we integrated the well-characterized monoclonal antibody into an electrochemical biosensor and demonstrated its high specificity and sensitivity capabilities in detecting pathogenic bacterial T3SS-associated antigens as well as intact bacteria. We foresee that in the near future it will be possible to design and develop a point-of-care biosensor with multiplexing capabilities for the detection of a panel of pathogenic bacteria.

The Perfect Predator: A Scientist's Race to Save Her Husband from a Deadly Superbug

The Perfect Predator: A Scientist's Race to Save Her Husband from a Deadly Superbug

TEIXOBACTIN - A GAME CHANGER ANTIBIOTIC

Ateam of scientist under the supervision of Kim Lewis from Northeastern University has discovered a novel antibiotic called Teixobactin, which kills the bacteria by inhibiting them from building their outer protein envelop. The bacterial resistance interference are key challenges to the global health. Teixobactin shows exceptional antibacterial activities against the range of pathogenic bacteria viz S.Aureus and Mycobacterium Tuberculosis. It is bactericidal and has many mode of operation, however it is one of the most important contribution in the modernization of medicine. However, the increase in Antibiotic resistance is at alarming rate and the ability of patient care through antibiotics is a challenge nowadays increment in Antibiotics resistance is among the top public health threats in the century 21". According to the Centers for Disease Control and Prevention (CDCP), around 23 thousand peoples die in every year in United States of America (USA) due to Antibiotic resistance. Whenever the patient is administered with an antibiotic the condition of the patient does not improve due to which more than 2 million people are sickened. The increase in Antibiotic resistance is much greater than the increase in epidemic diseases such as Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome (Al DS) or Ebola Virus Disease. The cost of human Antibiotic resistance crisis is estimated to be 300 million mortalities collectively by 2050. And it will also be the cause of declining graph of global economy of around $100 trillion. Production of new antibiotics in the 21" century seems to be difficult task to deal Teixobactin comes under new class of antibiotics. It is the first new antibiotic that is being isolated from bacteria after 30 years. After teixobactin's isolation from the soil full of bacteria, another novel class of antibiotics are discovered known as Malacidine, which was revealed later in 2018

Comprehensive prediction of secondary metabolite structure and biological activity from microbial genome sequences

Novel antibiotics are urgently needed to address the looming global crisis of antibiotic resistance. Historically, the primary source of clinically used antibiotics has been microbial secondary metabolism. Microbial genome sequencing has revealed a plethora of uncharacterized natural antibiotics that remain to be discovered. However, the isolation of these molecules is hindered by the challenge of linking sequence information to the chemical structures of the encoded molecules. Here, we present PRISM 4, a comprehensive platform for prediction of the chemical structures of genomically encoded antibiotics, including all classes of bacterial antibiotics currently in clinical use. The accuracy of chemical structure prediction enables the development of machine-learning methods to predict the likely biological activity of encoded molecules. We apply PRISM 4 to chart secondary metabolite biosynthesis in a collection of over 10,000 bacterial genomes from both cultured isolates and metagenomic datasets, revealing thousands of encoded antibiotics. PRISM 4 is freely available as an interactive web application at http://prism.adapsyn.com.

Plant resistome profiling in evolutionary old bog vegetation provides new clues to understand emergence of multi-resistance

The expanding antibiotic resistance crisis calls for a more in depth understanding of the importance of antimicrobial resistance genes (ARGs) in pristine environments. We, therefore, studied the microbiome associated with Sphagnum moss forming the main vegetation in undomesticated, evolutionary old bog ecosystems. In our complementary analysis of culture collections, metagenomic data and a fosmid library from different geographic sites in Europe, we identified a low abundant but highly diverse pool of resistance determinants, which targets an unexpectedly broad range of 29 antibiotics including natural and synthetic compounds. This derives both, from the extraordinarily high abundance of efflux pumps (up to 96%), and the unexpectedly versatile set of ARGs underlying all major resistance mechanisms. Multi-resistance was frequently observed among bacterial isolates, e.g. in Serratia, Rouxiella, Pandoraea, Paraburkholderia and Pseudomonas. In a search for novel ARGs, we identified the new class A β-lactamase Mm3. The native Sphagnum resistome comprising a highly diversified and partially novel set of ARGs contributes to the bog ecosystem´s plasticity. Our results reinforce the ecological link between natural and clinically relevant resistomes and thereby shed light onto this link from the aspect of pristine plants. Moreover, they underline that diverse resistomes are an intrinsic characteristic of plant-associated microbial communities, they naturally harbour many resistances including genes with potential clinical relevance.

Phage-antibiotic combinations: a promising approach to constrain resistance evolution in bacteria.

Antibiotic resistance has reached dangerously high levels throughout the world. A growing number of bacteria pose an urgent, serious, and concerning threat to public health. Few new antibiotics are available to clinicians and only few are in development, highlighting the need for new strategies to overcome the antibiotic resistance crisis. Combining existing antibiotics with phages, viruses the infect bacteria, is an attractive and promising alternative to standalone therapies. Phage-antibiotic combinations have been shown to suppress the emergence of resistance in bacteria, and sometimes even reverse it. Here, we discuss the mechanisms by which phage-antibiotic combinations reduce resistance evolution, and the potential limitations these mechanisms have in steering microbial resistance evolution in a desirable direction. We also emphasize the importance of gaining a better understanding of mechanisms behind physiological and evolutionary phage-antibiotic interactions in complex in-patient environments.

Ethnobotany and the Role of Plant Natural Products in Antibiotic Drug Discovery.

The crisis of antibiotic resistance necessitates creative and innovative approaches, from chemical identification and analysis to the assessment of bioactivity. Plant natural products (NPs) represent a promising source of antibacterial lead compounds that could help fill the drug discovery pipeline in response to the growing antibiotic resistance crisis. The major strength of plant NPs lies in their rich and unique chemodiversity, their worldwide distribution and ease of access, their various antibacterial modes of action, and the proven clinical effectiveness of plant extracts from which they are isolated. While many studies have tried to summarize NPs with antibacterial activities, a comprehensive review with rigorous selection criteria has never been performed. In this work, the literature from 2012 to 2019 was systematically reviewed to highlight plant-derived compounds with antibacterial activity by focusing on their growth inhibitory activity. A total of 459 compounds are included in this Review, of which 50.8% are phenolic derivatives, 26.6% are terpenoids, 5.7% are alkaloids, and 17% are classified as other metabolites. A selection of 183 compounds is further discussed regarding their antibacterial activity, biosynthesis, structure-activity relationship, mechanism of action, and potential as antibiotics. Emerging trends in the field of antibacterial drug discovery from plants are also discussed. This Review brings to the forefront key findings on the antibacterial potential of plant NPs for consideration in future antibiotic discovery and development efforts.

Antibiotic Resistance Crisis in Urinary Tract Infections Utis in Egypt

Abstract Introduction/Objective Bacterial adaptation to antibiotics has been very successful. Over the past decade, the increase in antibiotic resistance has generated considerable medical problems. UTIs are one of the most common community-onset infections. The emergence of resistance to all classes of antibiotics in previously susceptible bacterial pathogens is a major challenge to infectious disease medicine. Thus, it is important that we forcefully implement strategies to reduce the rate of appearance and spread of resistant bacteria to allow new drug discovery to catch up with bacterial resistance development. Objectives: Methods The aim of this study is to predict the percentage of urine cultures antibiotic resistance in patients with UTIs in Egypt. Subjects and methods: A total of 200 subjects were enrolled in this study from The Delta region in Egypt; 38% males and 62% females with a median age of 39 years and 35 years respectively. Identification of the isolated organisms was identified by the cultural characters (Morphological characters of the purified bacterial isolates were carried out according to the colony characters, Gram stain reaction and biochemical tests for each organism using a standard semi-automated technique Results 98 cultures (49%) were observed to have resistance to 3- 5 classes of antibiotics including, 98% Cephalosporins, 85% β-lactam inhibitors and 71% fluoroquinolones; 66 females (57 gram -ve stain and 9 gram +ve stain) and 33 males (27gm -ve stain, 6gm +ve stain). 82 cultures (41%) were not resistant to any classes.; 32 males (28 gram -ve stain and 3 gram +ve stain) and 50 females (45 gram -ve stain and 5 gram +ve stain). 19 cultures (9.5%) were observed to be resistant to all antibiotics.; 12 males (11 gram -ve stain and 1 gram +ve stain) and 7 females (2 gram -ve stain and 5 gram +ve stain). Conclusion This study highlights the highest antibiotic resistance associated with urinary tract infection in Egypt as well as the classification of the organisms. The high resistance percentage is due to the overuse of antibiotics by public and inappropriate antibiotic prescribing. Antibiotics are unregulated and available over the counter without a prescription in Egypt which makes it easily accessible. We recommend regulating the use of antibiotics and lunch antimicrobial stewardship programs in Egypt.

The Synergistic Effect of Mud Crab Antimicrobial Peptides Sphistin and Sph12-38 With Antibiotics Azithromycin and Rifampicin Enhances Bactericidal Activity Against Pseudomonas Aeruginosa.

Overuse or abuse of antibiotics has undoubtedly accelerated the increasing prevalence of global antibiotic resistance crisis, and thus, people have been trying to explore approaches to decrease dosage of antibiotics or find new antibacterial agents for many years. Antimicrobial peptides (AMPs) are the ideal candidates that could kill pathogens and multidrug-resistant bacteria either alone or in combination with conventional antibiotics. In the study, the antimicrobial efficacy of mud crab Scylla paramamosain AMPs Sphistin and Sph12−38 in combination with eight selected antibiotics was evaluated using a clinical pathogen, Pseudomonas aeruginosa. It was interesting to note that the in vitro combination of rifampicin and azithromycin with Sphistin and Sph12−38 showed significant synergistic activity against P. aeruginosa. Moreover, an in vivo study was carried out using a mouse model challenged with P. aeruginosa, and the result showed that the combination of Sph12−38 with either rifampicin or azithromycin could significantly promote the healing of wounds and had the healing time shortened to 4–5 days compared with 7–8 days in control. The underlying mechanism might be due to the binding of Sphistin and Sph12−38 with P. aeruginosa lipopolysaccharides (LPS) and subsequent promotion of the intracellular uptake of rifampicin and azithromycin. Taken together, the significant synergistic antibacterial effect on P. aeruginosa in vitro and in vivo conferred by the combination of low dose of Sphistin and Sph12−38 with low dose of rifampicin and azithromycin would be beneficial for the control of antibiotic resistance and effective treatment of P. aeruginosa-infected diseases in the future.

Addressing the global antibiotic resistance crisis through a microbiology undergraduate course-based research experience (CURE)

Objective Lens by editor Dr. John McKillip

English

Infections caused by Acinetobacter baumannii and other pathogenic bacteria are a worldwide concern due to their increasingly prevalent multidrug resistance. World leaders and health organizations across the globe have voiced their concerns over antibiotic resistance and the critical need for the development of novel antibiotics. Although the number of new antibiotic drugs entering the marketplace in recent years has been limited, it is encouraging to note that there are many initiatives in academia, industry, and government focused on this issue. This study outlines the investigation of a publicly available library of Traditional Chinese Medicine extracts to discover new compounds that could potentially inhibit the growth of a multidrug-resistant A. baumannii strain. Within this library of over 600 natural product samples, two individual extracts were found which exhibited over 50% mean growth inhibition of this bacterial strain at an extract concentration of 10 µg/mL. Fractionation of these two extracts into more isolated compounds also resulted in inhibitory activity. The results of this study highlight the value of this natural products library as a resource for further investigation in discovering anti-infective agents, especially during this global crisis of antibiotic resistance. Key words: Traditional Chinese Medicine, Acinetobacter baumannii, growth inhibition, antibiotic resistance.

Bacteriophages as drivers of bacterial virulence and their potential for biotechnological exploitation.

Bacteria-infecting viruses (phages) and their hosts maintain an ancient and complex relationship. Bacterial predation by lytic phages drives an ongoing phage-host arms race, whereas temperate phages initiate mutualistic relationships with their hosts upon lysogenization as prophages. In human pathogens, these prophages impact bacterial virulence in distinct ways: by secretion of phage-encoded toxins, modulation of the bacterial envelope, mediation of bacterial infectivity and the control of bacterial cell regulation. This review builds the argument that virulence-influencing prophages hold extensive, unexplored potential for biotechnology. More specifically, it highlights the development potential of novel therapies against infectious diseases, to address the current antibiotic resistance crisis. First, designer bacteriophages may serve to deliver genes encoding cargo proteins which repress bacterial virulence. Secondly, one may develop small molecules mimicking phage-derived proteins targeting central regulators of bacterial virulence. Thirdly, bacteria equipped with phage-derived synthetic circuits which modulate key virulence factors could serve as vaccine candidates to prevent bacterial infections. The development and exploitation of such antibacterial strategies will depend on the discovery of other prophage-derived, virulence control mechanisms and, more generally, on the dissection of the mutualistic relationship between temperate phages and bacteria, as well as on continuing developments in the synthetic biology field.

The Unique Role That WHO Could Play in Implementing Phage Therapy to Combat the Global Antibiotic Resistance Crisis.

The Unique Role That WHO Could Play in Implementing Phage Therapy to Combat the Global Antibiotic Resistance Crisis.