Antivirulence Therapy- A Promising Alternative Technique for Antibiotic Resistance

Author(s):  
S.P. Zine ◽  
Ankita Rai ◽  
Parth Mehta ◽  
Sayli Sawant
eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Allison L Hicks ◽  
Stephen M Kissler ◽  
Tatum D Mortimer ◽  
Kevin C Ma ◽  
George Taiaroa ◽  
...  

Genotype-based diagnostics for antibiotic resistance represent a promising alternative to empiric therapy, reducing inappropriate antibiotic use. However, because such assays infer resistance based on known genetic markers, their utility will wane with the emergence of novel resistance. Maintenance of these diagnostics will therefore require surveillance to ensure early detection of novel resistance variants, but efficient strategies to do so remain undefined. We evaluate the efficiency of targeted sampling approaches informed by patient and pathogen characteristics in detecting antibiotic resistance and diagnostic escape variants in Neisseria gonorrhoeae, a pathogen associated with a high burden of disease and antibiotic resistance and the development of genotype-based diagnostics. We show that patient characteristic-informed sampling is not a reliable strategy for efficient variant detection. In contrast, sampling informed by pathogen characteristics, such as genomic diversity and genomic background, is significantly more efficient than random sampling in identifying genetic variants associated with resistance and diagnostic escape.


2019 ◽  
Vol 133 (2) ◽  
pp. 139
Author(s):  
Daniel F. Brunton

Making identifiable herbarium vouchers of the minute aquatic vascular plant duckmeal, Wolffia (Lemnoideae; Araceae) has typically required plants to be preserved in transparent, space-consuming vials that are fragile, difficult to work with, and labourious to prepare. An alternative technique for dry-mounting Wolffia within a layer of transparent, acid-free glue presents a promising alternative. Although the largely water-filled individual plants still compress substantially, this preparation technique results in specimens that retain their colour, size, and, most important, their shape. This greatly enhances the possibility of confident identification and simplifies both specimen preparation and storage.


2020 ◽  
Vol 10 (01) ◽  
pp. 106-113
Author(s):  
Hussain A. Hamza ◽  
Nasreen R. Jber

Methicillin-resistant Staphylococcus aureus (MRSA) is a S. aureus that resistant to β-lactam antibiotics (e.g., Cefoxitin and Oxacillin). MRSA has a tremendous capacity to develop resistance to other classes of antibiotics and forming a real threat to patients. The process of exploring a new tactic of non-antibiotic treatments has become an urgent need. A bacteriophage is one of the possible treatments that strongly suggested. Bacteriophages are viruses that infect bacteria as a natural host with a bactericidal capability against multidrug-resistant bacteria that do not respond to conventional antibiotics. The current study investigates the lytic efficacy of phage-cocktail in vitro, specifically against S. aureus isolated from skin infections and find out the possible association of phage-antibiotic resistance. A total of 43 isolates of Methicillin-resistant staphylococcus aureus were isolated from skin infections. The isolates are distributed as (10 isolates of burn, 4 isolates of diabetic foot ulcer, 7 isolates of surgical wounds, 3 isolates of pressure ulcer, and 19 of skin and soft tissue infection). The isolates exhibited variant antibiotic susceptibility against 12 antibiotics (Cefoxitin FOX, Vancomycin VAN, Oxacillin OX, Rifampin RA, Chloramphenicol C, Nitrofurantoin F, Clindamycin DA, Azithromycin AZM, Amikacin AK, Trimethoprim-sulfamethoxazole SXT, Ciprofloxacin CIP, and Gentamicin CN). A bacteriophage cocktail was isolated using a phage-enrichment technique, high titer phage lysate (5*109 pfu/ml) was obtained and investigated against 43 MRSA isolates. The phage-cocktail showed high specificity to S. aureus but variable susceptibility to 43 MRSA isolates. It was observed that there was no association (p greater than 0.05) between phage and antibiotic resistance of (FOX, OX, VAN, RA, C, F, and DA) where the significant association was observed (p less than 0.05) with (AZM, AK, SXT, CIP, and CN). Significantly, the more antibiotic-resistant isolates exhibited more sensitivity to phage-cocktail, which represents a promising alternative to antibiotics that do not affect with increasing antibiotic resistance.


Author(s):  
Allison L. Hicks ◽  
Stephen M. Kissler ◽  
Tatum D. Mortimer ◽  
Kevin C. Ma ◽  
George Taiaroa ◽  
...  

AbstractGenotype-based diagnostics for antibiotic resistance represent a promising alternative to empiric therapy, reducing inappropriate and ineffective antibiotic use. However, because such assays infer resistance phenotypes based on the presence or absence of known genetic markers, their utility will wane in response to the emergence of novel resistance. Maintenance of these diagnostics will therefore require surveillance designed to ensure early detection of novel resistance variants, but efficient strategies to do so remain to be defined. Here, we evaluate the efficiency of targeted sampling approaches informed by patient and pathogen characteristics in detecting genetic variants associated with antibiotic resistance or diagnostic escape in Neisseria gonorrhoeae, focusing on this pathogen because of its high burden of disease, the imminent threat of treatment resistance, and the use and ongoing development of genotype-based diagnostics. We show that incorporating patient characteristics, such as demographics, geographic regions, or anatomical sites of isolate collection, into sampling approaches is not a reliable strategy for increasing variant detection efficiency. In contrast, sampling approaches informed by pathogen characteristics, such as genomic diversity and genomic background, are significantly more efficient than random sampling in identifying genetic variants associated with antibiotic resistance and diagnostic escape.


2019 ◽  
Vol 20 (15) ◽  
pp. 3806 ◽  
Author(s):  
María Vallet-Regí ◽  
Blanca González ◽  
Isabel Izquierdo-Barba

Both the prevalence of antibiotic resistance and the increased biofilm-associated infections are boosting the demand for new advanced and more effective treatment for such infections. In this sense, nanotechnology offers a ground-breaking platform for addressing this challenge. This review shows the current progress in the field of antimicrobial inorganic-based nanomaterials and their activity against bacteria and bacterial biofilm. Herein, nanomaterials preventing the bacteria adhesion and nanomaterials treating the infection once formed are presented through a classification based on their functionality. To fight infection, nanoparticles with inherent antibacterial activity and nanoparticles acting as nanovehicles are described, emphasizing the design of the carrier nanosystems with properties targeting the bacteria and the biofilm.


Antibiotics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 46
Author(s):  
Tamara Manso ◽  
Marta Lores ◽  
Trinidad de Miguel

Antibiotic resistance is a growing global problem that affects people, animals, the environment, and the economy. Many clinically relevant bacteria have become resistant to antibiotics, and this fact is emerging as one of the major threats to public health. The lack of new antibiotics, which is due to their time-consuming and costly development, exacerbates the problem. Therefore, it is necessary to identify new antimicrobial agents to treat bacterial and fungal infections. Plant extracts, which are valuable sources of bioactive compounds, mainly polyphenols, play an important role as a new strategy to combat pathogenic microorganisms. There is an extensive body of supporting evidence for the potent antibacterial and antifungal activities of polyphenols. Furthermore, some polyphenols show a synergistic effect when combined with antibiotics and antifungals, suggesting a promising alternative for therapeutic strategies against antibiotic resistance. However, only a few articles are found when searching the antibacterial or antifungal activities of polyphenols employing clinical isolates. Hence, this review focuses on the antimicrobial activity of polyphenols and extracts rich in polyphenols on clinical isolates, organized according to the World Health Organization priority pathogens classification.


2020 ◽  
Author(s):  
Cristina Herencias ◽  
Jerónimo Rodríguez-Beltrán ◽  
Ricardo León-Sampedro ◽  
Aida Alonso-del Valle ◽  
Jana Palkovičová ◽  
...  

AbstractCollateral sensitivity (CS) is a promising alternative approach to counteract the rising problem of antibiotic resistance (ABR). CS occurs when the acquisition of resistance to one antibiotic produces increased susceptibility to a second antibiotic. For CS to be widely applicable in clinical practice, it would need to be effective against the different resistance mechanisms available to bacteria. Recent studies have focused on CS strategies designed against ABR mediated by chromosomal mutations. However, one of the main drivers of ABR in clinically relevant bacteria is the horizontal transfer of ABR genes mediated by plasmids. Here, we report the first analysis of CS associated with the acquisition of complete ABR plasmids, including the clinically important carbapenem-resistance conjugative plasmid pOXA-48. In addition, we describe the conservation of CS in clinical E. coli isolates and its application to the selective elimination of plasmid-carrying bacteria. Our results provide new insights that establish the basis for developing CS-informed treatment strategies to combat plasmid-mediated ABR.


2019 ◽  
Vol 26 (13) ◽  
pp. 2297-2312 ◽  
Author(s):  
Xiaodan Cai ◽  
Weihao Zheng ◽  
Zigang Li

Background:The increasing threats of antibiotic resistance urge the need for developing new approaches to combat bacterial infections including those caused by Staphylococcus aureus (S. aureus). Unlike conventional antibiotics that aim to kill bacteria or inhibit their growth, targeting bacterial virulence may be a promising alternative approach, which imposes less selective pressure for antibiotic resistance in future generations.Objective:Our goal is to provide a systematic review about developing high-throughput screening (HTS) strategies for the identification of inhibitors targeting virulence of S. aureus. We also describe an overview of virulence regulatory pathways for potential antivirulence targets.Methods:We focus on five potential targets or target families, including agr quorum sensing system, SarA/MgrA protein family, sortase A, Clp protease and eukaryotic-like Ser/Thr phosphatase (Stp1). For each target, we introduce its role in virulence regulation, summarize the HTS approaches that are used to identify novel anti-virulence inhibitors, and discuss the advantages and disadvantages of these strategies.Conclusion:The discovery of anti-virulence inhibitors via HTS underlines the promising potential of anti-virulence therapy for S. aureus. The development of HTS strategies can facilitate the identification of novel anti-virulence inhibitors for combating S. aureus infection, and may also advance our understanding on virulence regulation in S. aureus.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243947
Author(s):  
Katherine E. Macdonald ◽  
Helen J. Stacey ◽  
Gillian Harkin ◽  
Lesley M. L. Hall ◽  
Matthew J. Young ◽  
...  

Infections of diabetic foot ulcers are common, generally recalcitrant and often complicated by antibiotic resistance. Alternative antimicrobial strategies are needed. Phage therapy is a promising alternative that is being rediscovered. Despite phage therapy’s 100-year history, there have been no investigations into patient thoughts and concerns. This study aimed to explore patient awareness of and concern about antibiotic resistance and gain insight into the perceptions of phage therapy among a patient group that could potentially benefit from phage therapy. Patients with an active or resolved (healed or amputated) diabetic foot ulcer were eligible to participate. A survey was distributed digitally to eligible patients across Scotland via the NHS Research Scotland Diabetes Network and hard copies were available in diabetic foot clinics at the Royal Infirmary of Edinburgh and Queen Elizabeth University Hospital, Glasgow. A focus group of five survey respondents was held in Glasgow. Fifty-five survey responses were obtained. There was a high level of awareness (76.4%; N = 55) and concern (83.3%; N = 54) about antibiotic resistance. While largely aware of viruses, most patients had not heard of phage or phage therapy. Patients were no more concerned about phage than antibiotic therapy, with most suggesting more information could alleviate any concerns. Patient acceptability of phage therapy was high, a finding confirmed by the focus group. Patients are concerned about antibiotic resistance and supportive of ‘new’ antimicrobials. We have demonstrated that patients are supportive, enthusiastic and accepting of phage therapy. Although ‘Western’ phage therapy remains in its infancy, an understanding of patient ideas, concerns and expectations will be important in eventually shaping and successfully reintroducing phage therapy.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Cristina Herencias ◽  
Jerónimo Rodríguez-Beltrán ◽  
Ricardo León-Sampedro ◽  
Aida Alonso-del Valle ◽  
Jana Palkovičová ◽  
...  

Collateral sensitivity (CS) is a promising alternative approach to counteract the rising problem of antibiotic resistance (ABR). CS occurs when the acquisition of resistance to one antibiotic produces increased susceptibility to a second antibiotic. Recent studies have focused on CS strategies designed against ABR mediated by chromosomal mutations. However, one of the main drivers of ABR in clinically relevant bacteria is the horizontal transfer of ABR genes mediated by plasmids. Here, we report the first analysis of CS associated with the acquisition of complete ABR plasmids, including the clinically important carbapenem-resistance conjugative plasmid pOXA-48. In addition, we describe the conservation of CS in clinical E. coli isolates and its application to selectively kill plasmid-carrying bacteria. Our results provide new insights that establish the basis for developing CS-informed treatment strategies to combat plasmid-mediated ABR.


Sign in / Sign up

Export Citation Format

Share Document