scholarly journals Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

2018 ◽  
Vol 14 ◽  
pp. 2607-2617 ◽  
Author(s):  
Matthew B Calvert ◽  
Varsha R Jumde ◽  
Alexander Titz

The rapid development of antimicrobial resistance is threatening mankind to such an extent that the World Health Organization expects more deaths from infections than from cancer in 2050 if current trends continue. To avoid this scenario, new classes of anti-infectives must urgently be developed. Antibiotics with new modes of action are needed, but other concepts are also currently being pursued. Targeting bacterial virulence as a means of blocking pathogenicity is a promising new strategy for disarming pathogens. Furthermore, it is believed that this new approach is less susceptible towards resistance development. In this review, recent examples of anti-infective compounds acting on several types of bacterial targets, e.g., adhesins, toxins and bacterial communication, are described.

Author(s):  
Rita M Pinto ◽  
Daniela Lopes-de-Campos ◽  
M Cristina L Martins ◽  
Patrick Van Dijck ◽  
Cláudia Nunes ◽  
...  

ABSTRACT Staphylococcus aureus (S. aureus) is considered by the World Health Organization as a high priority pathogen for which new therapies are needed. This is particularly important for biofilm implant-associated infections once the only available treatment option implies a surgical procedure combined with antibiotic therapy. Consequently, these infections represent an economic burden for Healthcare Systems. A new strategy has emerged to tackle this problem: for small bugs, small particles. Here, we describe how nanotechnology-based systems have been studied to treat S. aureus biofilms. Their features, drawbacks and potentialities to impact the treatment of these infections are highlighted. Furthermore, we also outline biofilm models and assays required for preclinical validation of those nanosystems to smooth the process of clinical translation.


2006 ◽  
Vol 1 (7) ◽  
pp. 1934578X0600100
Author(s):  
Costas Demetzos

Nanotechnology is a challenging field in science and its application in medicine will bring significant advantages in the treatment of diseases. According to the World Health Organization there is a need for improved therapies against cancer, AIDS and Alzheimer's disease. The new therapies include the design of drug delivery systems, which are able to deliver new bioactive natural products to the target tissues. Dendrimers are hyperbranched polymers with well defined structure and molecular weight; they are composed of a central core and repeated branching units; they have a globular shape, low polydispersity and large void internal spaces that can be used for the encapsulation and delivery of many classes of compounds. Nanosystems, such as dendrimers, can achieve successful administration of poorly water-soluble compounds and those with narrow therapeutic indices.


2013 ◽  
Vol 2 (1) ◽  
Author(s):  
Zhu Yang ◽  
Mingxin Li ◽  
Wen Chen ◽  
Alexander Peters

<p>More and more mammalian cells especially continuous cell lines were used to produce vaccines and therapeutic biological products with the rapid development of biomedical technologies. Therefore, more attention should be paid from drug regulatory authorities to the safety of biological products especially quality control of residual DNA and RNA. World Health Organization has evaluated the methods commonly used in vaccine manufacture for their ability to reduce the biological activity of DNA. Benzonase endonuclease is frequently used during the production of vaccines and can degrade all nucleic acid sequences down to oligonucleotides of approximately 3 to 5 base pairs.</p>


2021 ◽  
Vol 3 (6) ◽  
pp. 52-55
Author(s):  
Selia Chowdhury ◽  
Mehedi Hasan Bappy

The unprecedented consequences brought by the COVID pandemic are still going on, the virus hasn’t been tamed yet. It is evolving through mutations to consistently being a risk to public health. Recently, the Delta variant has been declared as the variant of concern by the World Health Organization (WHO). In this article, a subvariant of Delta known as Delta Plus has been presented to provide a relevant foundation for future research works. The evolution, pathogenesis, associated symptoms, suggested prevention and treatments, vaccine efficacy, and current trends of transmission of Delta Plus variant of SARS-CoV-2 are reviewed and discussed.


Author(s):  
Mark S. Butler ◽  
Valeria Gigante ◽  
Hatim Sati ◽  
Sarah Paulin ◽  
Laila Al-Sulaiman ◽  
...  

There is an urgent global need for new strategies and drugs to control and treat multi-drug resistant bacterial infections. In 2017, the World Health Organization (WHO) released a list of 12 antibiotic-resistant priority pathogens and began to critically analyze the antibacterial clinical pipeline. This review analyzes ‘traditional’ and ‘non-traditional’ antibacterial agents and modulators in clinical development current on 30 June 2021 with activity against the WHO priority pathogens, mycobacteria and Clostridioides difficile. Since 2017, 12 new antibacterial drugs have been approved globally, but only vaborbactam belongs to a new antibacterial class. Also innovative is the cephalosporin derivative cefiderocol, which incorporates an iron-chelating siderophore that facilitates Gram-negative bacteria cell entry. Overall, there were 76 antibacterial agents in clinical development (45 traditional and 31 non-traditional) with 28 in Phase 1, 32 in Phase 2, 12 in Phase 3 and four under regulatory evaluation. Forty-one out of 76 (54%) targeted WHO priority pathogens, 16 (21%) against mycobacteria, 15 (20%) against C. difficile and 4 (5%) are non-traditional agents with broad spectrum effects. Nineteen of the 76 antibacterial agents have new pharmacophores and four of these have new modes of actions not previously exploited by marketed antibacterial drugs. Despite there being 76 antibacterial clinical candidates, this analysis indicated that there were still relatively few clinically differentiated antibacterial agents in late-stage clinical development, especially against critical Priority Pathogens. We believe that future antibacterial R&D should focus on the development of innovative and clinically differentiated candidates that have clear and feasible progression pathways to the market.


2020 ◽  
Vol 12 (22) ◽  
pp. 2035-2065
Author(s):  
Liam J Stephens ◽  
Melissa V Werrett ◽  
Adam C Sedgwick ◽  
Steven D Bull ◽  
Philip C Andrews

As bacteria continue to develop resistance to our existing treatment options, antibiotic innovation remains overlooked. If current trends continue, then we could face the stark reality of a postantibiotic era, whereby routine bacterial infections could once again become deadly. In light of a warning signaled by the WHO, a number of new initiatives have been established in the hope of reinvigorating the antibiotic drug development pipeline. In this perspective, we aim to summarize some of these initiatives and funding options, as well as providing an insight into the predicament that we face. Using clinical trials data, company website information and the most recent press releases, a current update of the antibiotic drug development pipeline is also included.


2015 ◽  
Vol 51 (1) ◽  
pp. 53-58
Author(s):  
Iwona Bil-Lula ◽  
Anna Krzywonos-Zawadzka

Obesity, which is a pathological and excessive accumulation of body fat (WHO; World Health Organization), is the problem undertaken in the world literature for several decades. Significant mortality due to the obesity comorbidities is the basis to undertake an intensive work on the new preventive and therapeutic strategies worldwide. Nevertheless, due to the multifactorial origin of obesity and the growing number of obese subjects, the effectiveness of these strategies appears to be highly limited. Besides to the traditionally recognized etiological factors of obesity, many reports showing an association of infectious agents and uncontrolled weight gain have been published recently. In this paper we present an overview of reports confirming the association between infections and obesity. Data showed that a specific viral and bacterial infections as well as infections with protozoa and prions are associated with the increased intracellular accumulation of lipids, hypertrophy and hyperplasia of adipose tissue, body weight gain, increase of BMI and changes in lipid metabolism. These infections can serve as direct causal agents, but they can also interact with other environmental factors, thus increasing the predisposition to the development of obesity. There are at least a few hypotheses on the pathogenesis of “infectobesity.” There are some reports describing the damage of the central nervous system and hence the endocrine glands dysfunction due to infection, increased insulin susceptibility of infected cells, reduced production and release of leptin, increased glucose and fatty acids transport into adipocytes and inflammatory basis for infectobesity. Undoubtedly, awareness of the relationship between infections and obesity brings us closer to develop the effective preventive and therapeutic strategies, but it also raises the question about other, so far underestimated, environmental factors that increase the predisposition to obesity.


2020 ◽  
Vol 1 (4) ◽  
pp. 74-79 ◽  
Author(s):  
Thomas E. Baldock ◽  
Scott M. Bolam ◽  
Ryan Gao ◽  
Mark F. Zhu ◽  
Michael P. J. Rosenfeldt ◽  
...  

Aim The coronavirus disease 2019 (COVID-19) pandemic presents significant challenges to healthcare systems globally. Orthopaedic surgeons are at risk of contracting COVID-19 due to their close contact with patients in both outpatient and theatre environments. The aim of this review was to perform a literature review, including articles of other coronaviruses, to formulate guidelines for orthopaedic healthcare staff. Methods A search of Medline, EMBASE, the Cochrane Library, World Health Organization (WHO), and Centers for Disease Control and Prevention (CDC) databases was performed encompassing a variety of terms including ‘coronavirus’, ‘covid-19’, ‘orthopaedic’, ‘personal protective environment’ and ‘PPE’. Online database searches identified 354 articles. Articles were included if they studied any of the other coronaviruses or if the basic science could potentially applied to COVID-19 (i.e. use of an inactivated virus with a similar diameter to COVID-19). Two reviewers independently identified and screened articles based on the titles and abstracts. 274 were subsequently excluded, with 80 full-text articles retrieved and assessed for eligibility. Of these, 66 were excluded as they compared personal protection equipment to no personal protection equipment or referred to prevention measures in the context of bacterial infections. Results There is a paucity of high quality evidence surrounding COVID-19. This review collates evidence from previous coronavirus outbreaks to put forward recommendations for orthopaedic surgeons during the COVID-19 pandemic. The key findings have been summarized and interpreted for application to the orthopaedic operative setting. Conclusion For COVID-19 positive patients, minimum suggested PPE includes N95 respirator, goggles, face shield, gown, double gloves, and surgical balaclava. Space suits not advised. Be trained in the correct technique of donning and doffing PPE. Use negative pressure theatres if available. Minimize aerosolization and its effects (smoke evacuation and no pulse lavage). Minimize further unnecessary patient-staff contact (dissolvable sutures, clear dressings, split casts).


2017 ◽  
Vol 114 (16) ◽  
pp. 4055-4059 ◽  
Author(s):  
David E. Bloom ◽  
Steven Black ◽  
Rino Rappuoli

Infectious diseases are now emerging or reemerging almost every year. This trend will continue because a number of factors, including the increased global population, aging, travel, urbanization, and climate change, favor the emergence, evolution, and spread of new pathogens. The approach used so far for emerging infectious diseases (EIDs) does not work from the technical point of view, and it is not sustainable. However, the advent of platform technologies offers vaccine manufacturers an opportunity to develop new vaccines faster and to reduce the investment to build manufacturing facilities, in addition to allowing for the possible streamlining of regulatory processes. The new technologies also make possible the rapid development of human monoclonal antibodies that could become a potent immediate response to an emergency. So far, several proposals to approach EIDs have been made independently by scientists, the private sector, national governments, and international organizations such as the World Health Organization (WHO). While each of them has merit, there is a need for a global governance that is capable of taking a strong leadership role and making it attractive to all partners to come to the same table and to coordinate the global approach.


2021 ◽  
Vol 22 (8) ◽  
pp. 4042
Author(s):  
Vanessa Arato ◽  
Maria Michelina Raso ◽  
Gianmarco Gasperini ◽  
Francesco Berlanda Scorza ◽  
Francesca Micoli

Klebsiella pneumoniae (Kp) is an opportunistic pathogen and the leading cause of healthcare-associated infections, mostly affecting subjects with compromised immune systems or suffering from concurrent bacterial infections. However, the dramatic increase in hypervirulent strains and the emergence of new multidrug-resistant clones resulted in Kp occurrence among previously healthy people and in increased morbidity and mortality, including neonatal sepsis and death across low- and middle-income countries. As a consequence, carbapenem-resistant and extended spectrum β-lactamase-producing Kp have been prioritized as a critical anti-microbial resistance threat by the World Health Organization and this has renewed the interest of the scientific community in developing a vaccine as well as treatments alternative to the now ineffective antibiotics. Capsule polysaccharide is the most important virulence factor of Kp and plays major roles in the pathogenesis but its high variability (more than 100 different types have been reported) makes the identification of a universal treatment or prevention strategy very challenging. However, less variable virulence factors such as the O-Antigen, outer membrane proteins as fimbriae and siderophores might also be key players in the fight against Kp infections. Here, we review elements of the current status of the epidemiology and the molecular pathogenesis of Kp and explore specific bacterial antigens as potential targets for both prophylactic and therapeutic solutions.


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