Challenges and opportunities for cheat therapy in the control of bacterial infections

2022 ◽  
Author(s):  
James Gurney ◽  
Camille Simonet ◽  
Kristofer Wollein Waldetoft ◽  
Sam P. Brown

Bacterial pathogens can be highly social, communicating and cooperating within multi-cellular groups to make us sick. Manipulating these behaviors might have therapeutic benefits.

2017 ◽  
Vol 1 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Giordano Rampioni ◽  
Paolo Visca ◽  
Livia Leoni ◽  
Francesco Imperi

Antibiotic resistance is a serious public health concern at the global level. Available antibiotics have saved millions of lives, but are progressively losing their efficacy against many bacterial pathogens, and very few new antibiotics are being developed by the pharmaceutical industry. Over the last few decades, progress in understanding the pathogenic process of bacterial infections has led researchers to focus on bacterial virulence factors as potential targets for ‘antivirulence' drugs, i.e. compounds which inhibit the ability of bacteria to cause damage to the host, as opposed to inhibition of bacterial growth which is typical of antibiotics. Hundreds of virulence inhibitors have been examined to date in vitro and/or in animal models, but only a few were entered into clinical trials and none were approved, thus hindering the clinical validation of antivirulence therapy. To breathe new life into antivirulence research and speed-up its transfer to the clinic, antivirulence activities have also been sought in drugs already approved for different therapeutic purposes in humans. If effective, these drugs could be repositioned for antivirulence therapy and have an easier and faster transfer to the clinic. In this work we summarize the approaches which have led to the identification of repurposing candidates with antivirulence activities, and discuss the challenges and opportunities related to antivirulence therapy and drug repurposing. While this approach undoubtedly holds promise for boosting antivirulence drug research, some important issues remain to be addressed in order to make antivirulence drugs viable alternatives to traditional antibacterials.


Chemosensors ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 49
Author(s):  
Pushap Raj ◽  
Man Hwan Oh ◽  
Kyudong Han ◽  
Tae Yoon Lee

Bacterial infections have become a significant challenge in terms of public health, the food industry, and the environment. Therefore, it is necessary to address these challenges by developing a rapid, cost-effective, and easy-to-use biosensor for early diagnosis of bacterial pathogens. Herein, we developed a simple, label-free, and highly sensitive immunosensor based on electrochemical detection using the Au@MoS₂–PANI nanocomposite. The conductivity of the glassy carbon electrode is greatly enhanced using the Au@MoS₂–PANI nanocomposite and a self-assembled monolayer of mercaptopropionic acid on the gold nanoparticle surface was employed for the covalent immobilization of antibodies to minimize the nonspecific adsorption of bacterial pathogens on the electrode surface. The biosensor established a high selectivity and sensitivity with a low limit of detection of 10 CFU/mL, and detected Escherichia coli within 30 min. Moreover, the developed biosensor demonstrated a good linear detection range, practical utility in urine samples, and electrode regenerative studies.


Nanoscale ◽  
2022 ◽  
Author(s):  
Deepa Ghosh ◽  
Swati Kaushik ◽  
Jijo Thomas ◽  
Vineeta Panwar ◽  
Preethi Murugesan ◽  
...  

The extensive and indiscriminate use of antibiotics in the ongoing COVID-19 pandemic might significantly contribute to the growing number of multiple drug resistant (MDR) bacteria. With the dwindling pipeline of...


2019 ◽  
Vol 21 (2) ◽  
pp. 741-750 ◽  
Author(s):  
Zhi Ruan ◽  
Yunsong Yu ◽  
Ye Feng

Abstract Whole genome sequencing (WGS) has revolutionized the genotyping of bacterial pathogens and is expected to become the new gold standard for tracing the transmissions of bacterial infectious diseases for public health purposes. Traditional genomic epidemiology often uses WGS as a verification tool, namely, when a common source or epidemiological link is suspected, the collected isolates are sequenced for the determination of clonal relationships. However, increasingly frequent international travel and food transportation, and the associated potential for the cross-border transmission of bacterial pathogens, often lead to an absence of information on bacterial transmission routes. Here we introduce the concept of ‘reverse genomic epidemiology’, i.e. when isolates are inspected by genome comparisons to be sufficiently similar to one another, they are assumed to be a consequence of infection from a common source. Through BacWGSTdb (http://bacdb.org/BacWGSTdb/), a database we have developed for bacterial genome typing and source tracking, we have found that almost the entire analyzed 20 bacterial species exhibit the phenomenon of cross-border clonal dissemination. Five networks were further identified in which isolates sharing nearly identical genomes were collected from at least five different countries. Three of these have been documented as real infectious disease outbreaks, therefore demonstrating the feasibility and authority of reverse genomic epidemiology. Our survey and proposed strategy would be of potential value in establishing a global surveillance system for tracing bacterial transmissions and outbreaks; the related database and techniques require urgent standardization.


2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Ravinder Mettu ◽  
Chiang-Yun Chen ◽  
Chung-Yi Wu

AbstractGlycoconjugate vaccines based on bacterial capsular polysaccharides (CPS) have been extremely successful in preventing bacterial infections. The glycan antigens for the preparation of CPS based glycoconjugate vaccines are mainly obtained from bacterial fermentation, the quality and length of glycans are always inconsistent. Such kind of situation make the CMC of glycoconjugate vaccines are difficult to well control. Thanks to the advantage of synthetic methods for carbohydrates syntheses. The well controlled glycan antigens are more easily to obtain, and them are conjugated to carrier protein to from the so-call homogeneous fully synthetic glycoconjugate vaccines. Several fully glycoconjugate vaccines are in different phases of clinical trial for bacteria or cancers. The review will introduce the recent development of fully synthetic glycoconjugate vaccine.


2020 ◽  
Vol 19 (3) ◽  
pp. 365-371
Author(s):  
S Sindhu ◽  
S Murugan

for treating a new clinical condition takes time and consumes a lot of investment. Therefore, there is much attention given towards repurposing of old drugs for new therapy. Majority of drugs approved by FDA for a particular treatment has found applications in the treatment of various other clinical conditions too. In other words, it can be said as ‘reusing’ of a drug. This mini review focused on the use of repurposed drugs for bacterial infections and cancer treatment. Apart from the benefits of repurposing of drugs, there are some challenges needed to be addressed. Therefore, in this review paper the use of repurposed drugs in treatment of communicable (bacterial infections) and non-communicable (cancer) diseases were discussed. Bangladesh Journal of Medical Science Vol.19(3) 2020 p.365-371


2012 ◽  
Vol 56 (11) ◽  
pp. 5433-5441 ◽  
Author(s):  
Miles C. Duncan ◽  
Roger G. Linington ◽  
Victoria Auerbuch

ABSTRACTThe recent and dramatic rise of antibiotic resistance among bacterial pathogens underlies the fear that standard treatments for infectious disease will soon be largely ineffective. Resistance has evolved against nearly every clinically used antibiotic, and in the near future, we may be hard-pressed to treat bacterial infections previously conquered by “magic bullet” drugs. While traditional antibiotics kill or slow bacterial growth, an important emerging strategy to combat pathogens seeks to block the ability of bacteria to harm the host by inhibiting bacterial virulence factors. One such virulence factor, the type three secretion system (T3SS), is found in over two dozen Gram-negative pathogens and functions by injecting effector proteins directly into the cytosol of host cells. Without T3SSs, many pathogenic bacteria are unable to cause disease, making the T3SS an attractive target for novel antimicrobial drugs. Interdisciplinary efforts between chemists and microbiologists have yielded several T3SS inhibitors, including the relatively well-studied salicylidene acylhydrazides. This review highlights the discovery and characterization of T3SS inhibitors in the primary literature over the past 10 years and discusses the future of these drugs as both research tools and a new class of therapeutic agents.


2021 ◽  
Vol 12 ◽  
Author(s):  
Robin Smyth ◽  
Jim Sun

The global antimicrobial resistance crisis poses a significant threat to humankind in the coming decades. Challenges associated with the development of novel antibiotics underscore the urgent need to develop alternative treatment strategies to combat bacterial infections. Host-directed therapy is a promising new therapeutic strategy that aims to boost the host immune response to bacteria rather than target the pathogen itself, thereby circumventing the development of antibiotic resistance. However, host-directed therapy depends on the identification of druggable host targets or proteins with key functions in antibacterial defense. Protein Kinase R (PKR) is a well-characterized human kinase with established roles in cancer, metabolic disorders, neurodegeneration, and antiviral defense. However, its role in antibacterial defense has been surprisingly underappreciated. Although the canonical role of PKR is to inhibit protein translation during viral infection, this kinase senses and responds to multiple types of cellular stress by regulating cell-signaling pathways involved in inflammation, cell death, and autophagy – mechanisms that are all critical for a protective host response against bacterial pathogens. Indeed, there is accumulating evidence to demonstrate that PKR contributes significantly to the immune response to a variety of bacterial pathogens. Importantly, there are existing pharmacological modulators of PKR that are well-tolerated in animals, indicating that PKR is a feasible target for host-directed therapy. In this review, we provide an overview of immune cell functions regulated by PKR and summarize the current knowledge on the role and functions of PKR in bacterial infections. We also review the non-canonical activators of PKR and speculate on the potential mechanisms that trigger activation of PKR during bacterial infection. Finally, we provide an overview of existing pharmacological modulators of PKR that could be explored as novel treatment strategies for bacterial infections.


2014 ◽  
Vol 61 (3) ◽  
Author(s):  
Janusz Kocik ◽  
Marcin Niemcewicz ◽  
Izabela Winnicka ◽  
Aleksander Michalski ◽  
Agata Bielawska-Drózd ◽  
...  

The aim of this study was to conduct an epidemiological and laboratory surveillance of Influenza-Like Illnesses (ILI) in Polish Armed Forces, civilian military personnel and their families in 2011/2012 epidemic season, under the United States Department of Defense-Global Emerging Infections Surveillance and Response System (DoD-GEIS). ILI incidence data were analyzed in relation to age, gender, patient category as well as pathogen patterns. Multiple viral, bacterial and viral-bacterial co-infections were identified. Nose and throat swabs of active duty soldiers in the homeland country and in the NATO peacekeeping forces KFOR (Kosovo Force), as well as members of their families were tested for the presence of viral and bacterial pathogens. From October 2011 to May 2012, 416 specimens from ILI symptoms patients were collected and analyzed for the presence of viral and bacterial pathogens. Among viruses, coronavirus was the most commonly detected. In the case of bacterial infections, the most common pathogen was Staphylococcus aureus.


2019 ◽  
Vol 98 (4) ◽  
pp. 137-144

The paper describes the basic sources and principles of antibiotic therapy in contemporary medicine in which the ability to treat bacterial infections may be lost. The main reason for that is the increasing resistance of bacterial pathogens to antibiotics. A possible solution is to implement a comprehensive program of antibiotic stewardship incorporating adequate consideration of indication and selection of antimicrobial agents including appropriate duration and way of administration. Another important component of the comprehensive approach to bacterial resistance and antibiotic therapy is adequately applied antibiotic prophylaxis in surgery.


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