scholarly journals Highlights on the alternatives to antibiotic therapy against bacterial infection

2021 ◽  
Vol 11 (2) ◽  
pp. 194-203
Author(s):  
Bijayanta Sircar ◽  
Shyamapada Mandal
Keyword(s):  
Antimicrobial Peptides ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Scientific Data ◽  
New Drugs ◽  
Health Concern ◽  
Antibiotic Resistant ◽  
Effective Drugs ◽  
Emergence Of Resistance ◽  
Antibacterial Capacity

The antibiotic resistance among gram-positive and gram-negative pathogenic bacteria is of global health concern. This has prompted the development of new effective drugs. But the discovery and development of new drugs is slow, and the emergence of resistance to such new drugs, on the other hand, is rapid as well as continuous among the bacteria. Therefore, in tackling the emergence of antibiotic resistant pathogenic bacteria finding alternative ways is vital. This communication, based on the published scientific data, summarizes the antibacterial capacity of some naturally derived agents such as honey, phytocomponents, probiotics, and antimicrobial peptides that might bring new essence in biomedicine.  Keywords: Bacterial resistance, alternative therapeutics, honey, phytomedicine, probiotics, antimicrobial peptides.

Antibiotic adjuvants: a promising approach to combat multidrug resistant bacteria

2021 ◽  
Vol 22 ◽  
Author(s):  
Namita Sharma ◽  
Anil K. Chhillar ◽  
Sweety Dahiya ◽  
Pooja Choudhary ◽  
Aruna Punia ◽  
...  
Keyword(s):  
Drug Targets ◽  
Pathogenic Bacteria ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibacterial Drugs ◽  
Effective Strategies ◽  
The Impact ◽  
Emergence Of Resistance

The escalating emergence and prevalence of infections caused by multi-drug resistant (MDR) pathogenic bacteria accentuate the crucial need to develop novel and effectual therapeutic strategies to control this threat. Recent past surprisingly indicates a staggering decline in effective strategies against MDR. Different approaches have been employed to minimize the effect of resistance but the question still lingers over the astounding number of drugs already tried and tested to no avail, furthermore, the detection of new drug targets and the action of new antibacterial agents against already existing drug targets also complicate the condition. Antibiotic adjuvants are considered as one such promising approach for overcoming the bacterial resistance. Adjuvants can potentiate the action of generally adopted antibacterial drugs against MDR bacterial pathogens either by minimizing the impact and emergence of resistance or improving the action of antibacterial drugs. This review provides an overview of mechanism of antibiotic resistance, main types of adjuvants and their mode of action, achievements and progression.

scholarly journals Surface mediated cooperative interactions of drugs enhance mechanical forces for antibiotic action

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Joseph W. Ndieyira ◽  
Joe Bailey ◽  
Samadhan B. Patil ◽  
Manuel Vögtli ◽  
Matthew A. Cooper ◽  
...  
Keyword(s):  
Drug Target ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Mechanical Response ◽  
Solvable Model ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Bacterial Surface ◽  
Membrane Effects

Abstract The alarming increase of pathogenic bacteria that are resistant to multiple antibiotics is now recognized as a major health issue fuelling demand for new drugs. Bacterial resistance is often caused by molecular changes at the bacterial surface, which alter the nature of specific drug-target interactions. Here, we identify a novel mechanism by which drug-target interactions in resistant bacteria can be enhanced. We examined the surface forces generated by four antibiotics; vancomycin, ristomycin, chloroeremomycin and oritavancin against drug-susceptible and drug-resistant targets on a cantilever and demonstrated significant differences in mechanical response when drug-resistant targets are challenged with different antibiotics although no significant differences were observed when using susceptible targets. Remarkably, the binding affinity for oritavancin against drug-resistant targets (70 nM) was found to be 11,000 times stronger than for vancomycin (800 μM), a powerful antibiotic used as the last resort treatment for streptococcal and staphylococcal bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Using an exactly solvable model, which takes into account the solvent and membrane effects, we demonstrate that drug-target interactions are strengthened by pronounced polyvalent interactions catalyzed by the surface itself. These findings further enhance our understanding of antibiotic mode of action and will enable development of more effective therapies.

scholarly journals Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 2

2015 ◽  
Vol 60 (3) ◽  
pp. 1194-1201 ◽  
Author(s):  
G. L. Drusano ◽  
William Hope ◽  
Alasdair MacGowan ◽  
Arnold Louie
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Regulatory Review ◽  
Content Type ◽  
Drug Resistant Bacteria ◽  
Antibiotic Drug ◽  
New Chemical Entities

We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens likePseudomonas aeruginosa,Acinetobacterspp., and multidrug-resistant (MDR)Enterobacteriaceae. These lessons need to be applied to our old drugs as well to preserve them and to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects.

scholarly journals Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 1

2015 ◽  
Vol 60 (3) ◽  
pp. 1183-1193 ◽  
Author(s):  
G. L. Drusano ◽  
Arnold Louie ◽  
Alasdair MacGowan ◽  
William Hope
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Regulatory Review ◽  
Content Type ◽  
Drug Resistant Bacteria ◽  
Antibiotic Drug ◽  
New Chemical Entities

We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens likePseudomonas aeruginosa,Acinetobacterspp., and multidrug-resistant (MDR)Enterobacteriaceae. These lessons need to be applied to our old drugs to preserve them as well and need to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a corresponding resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects.

scholarly journals Futuristic Non-antibiotic Therapies to Combat Antibiotic Resistance: A Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Manoj Kumar ◽  
Devojit Kumar Sarma ◽  
Swasti Shubham ◽  
Manoj Kumawat ◽  
Vinod Verma ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Genetic Factors ◽  
Clinical Importance ◽  
Therapeutic Interventions ◽  
Anthropogenic Sources ◽  
Health Concern ◽  
Clinical Settings ◽  
Livestock Farming ◽  
Antibiotic Resistant ◽  
Microbial Drug Resistance

The looming problem of resistance to antibiotics in microorganisms is a global health concern. The drug-resistant microorganisms originating from anthropogenic sources and commercial livestock farming have posed serious environmental and health challenges. Antibiotic-resistant genes constituting the environmental “resistome” get transferred to human and veterinary pathogens. Hence, deciphering the origin, mechanism and extreme of transfer of these genetic factors into pathogens is extremely important to develop not only the therapeutic interventions to curtail the infections, but also the strategies to avert the menace of microbial drug-resistance. Clinicians, researchers and policymakers should jointly come up to develop the strategies to prevent superfluous exposure of pathogens to antibiotics in non-clinical settings. This article highlights the present scenario of increasing antimicrobial-resistance in pathogenic bacteria and the clinical importance of unconventional or non-antibiotic therapies to thwart the infectious pathogenic microorganisms.

scholarly journals Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

2020 ◽  
Vol 21 (24) ◽  
pp. 9552
Author(s):  
Stanislav R. Kurpe ◽  
Sergei Yu. Grishin ◽  
Alexey K. Surin ◽  
Alexander V. Panfilov ◽  
Mikhail V. Slizen ◽  
...  
Keyword(s):  
Biological Activity ◽  
Severe Acute Respiratory Syndrome ◽  
Antimicrobial Peptides ◽  
Pathogenic Bacteria ◽  
Molecular Design ◽  
Resistant Bacteria ◽  
Published Data ◽  
Antibiotic Resistant ◽  
High Prevalence ◽  
Artificial Origin

At present, much attention is paid to the use of antimicrobial peptides (AMPs) of natural and artificial origin to combat pathogens. AMPs have several points that determine their biological activity. We analyzed the structural properties of AMPs, as well as described their mechanism of action and impact on pathogenic bacteria and viruses. Recently published data on the development of new AMP drugs based on a combination of molecular design and genetic engineering approaches are presented. In this article, we have focused on information on the amyloidogenic properties of AMP. This review examines AMP development strategies from the perspective of the current high prevalence of antibiotic-resistant bacteria, and the potential prospects and challenges of using AMPs against infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

scholarly journals Antimicrobial Peptides as Probes in Biosensors Detecting Whole Bacteria: A Review

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1998 ◽  
Author(s):  
Éric Pardoux ◽  
Didier Boturyn ◽  
Yoann Roupioz
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Molecular Probes ◽  
Growth Potential ◽  
New Drugs ◽  
Diagnostic Tools ◽  
Label Free ◽  
Bacterial Membranes ◽  
Global Issue ◽  
Cost Efficient

Bacterial resistance is becoming a global issue due to its rapid growth. Potential new drugs as antimicrobial peptides (AMPs) are considered for several decades as promising candidates to circumvent this threat. Nonetheless, AMPs have also been used more recently in other settings such as molecular probes grafted on biosensors able to detect whole bacteria. Rapid, reliable and cost-efficient diagnostic tools for bacterial infection could prevent the spread of the pathogen from the earliest stages. Biosensors based on AMPs would enable easy monitoring of potentially infected samples, thanks to their powerful versatility and integrability in pre-existent settings. AMPs, which show a broad spectrum of interactions with bacterial membranes, can be tailored in order to design ubiquitous biosensors easily adaptable to clinical settings. This review aims to focus on the state of the art of AMPs used as the recognition elements of whole bacteria in label-free biosensors with a particular focus on the characteristics obtained in terms of threshold, volume of sample analysable and medium, in order to assess their workability in real-world applications.

scholarly journals Antimicrobial Action of Carbon Monoxide-Releasing Compounds

2007 ◽  
Vol 51 (12) ◽  
pp. 4303-4307 ◽  
Author(s):  
Lígia S. Nobre ◽  
João D. Seixas ◽  
Carlos C. Romão ◽  
Lígia M. Saraiva
Keyword(s):  
Carbon Monoxide ◽  
Mammalian Cells ◽  
Pathogenic Bacteria ◽  
Health Concern ◽  
Low Oxygen ◽  
Vascular Effects ◽  
Antibiotic Resistant ◽  
Therapeutic Drugs ◽  
Starting Point ◽  
Pathogen Colonization

ABSTRACT Carbon monoxide (CO) is endogenously produced in the human body, mainly from the oxidation of heme catalyzed by heme oxygenase (HO) enzymes. The induction of HO and the consequent increase in CO production play important physiological roles in vasorelaxation and neurotransmission and in the immune system. The exogenous administration of CO gas and CO-releasing molecules (CO-RMs) has been shown to induce vascular effects and to alleviate hypoxia-reoxygenation injury of mammalian cells. In particular, due to its anti-inflammatory, antiapoptotic, and antiproliferative properties, CO inhibits ischemic-reperfusion injury and provides potent cytoprotective effects during organ and cell transplantation. In spite of these findings regarding the physiology and biology of mammals, nothing is known about the action of CO on bacteria. In the present work, we examined the effect of CO on bacterial cell proliferation. Cell growth experiments showed that CO caused the rapid death of the two pathogenic bacteria tested, Escherichia coli and Staphylococcus aureus, particularly when delivered through organometallic CO-RMs. Of importance is the observation that the effectiveness of the CO-RMs was greater in near-anaerobic environments, as many pathogens are anaerobic organisms and pathogen colonization occurs in environments with low oxygen concentrations. Our results constitute the first evidence that CO can be utilized as an antimicrobial agent. We anticipate our results to be the starting point for the development of novel types of therapeutic drugs designed to combat antibiotic-resistant pathogens, which are widespread and presently a major public health concern.

scholarly journals Antimicrobial Peptides: A New Hope in Biomedical and Pharmaceutical Fields

2021 ◽  
Vol 11 ◽  
Author(s):  
Antonio Moretta ◽  
Carmen Scieuzo ◽  
Anna Maria Petrone ◽  
Rosanna Salvia ◽  
Michele Dario Manniello ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Inhibitory Peptides ◽  
Small Proteins ◽  
Ability To Act ◽  
New Antibiotics ◽  
Potential Applicability ◽  
Living Organisms ◽  
Enzyme I

Antibiotics are essential drugs used to treat pathogenic bacteria, but their prolonged use contributes to the development and spread of drug-resistant microorganisms. Antibiotic resistance is a serious challenge and has led to the need for new alternative molecules less prone to bacterial resistance. Antimicrobial peptides (AMPs) have aroused great interest as potential next-generation antibiotics, since they are bioactive small proteins, naturally produced by all living organisms, and representing the first line of defense against fungi, viruses and bacteria. AMPs are commonly classified according to their sources, which are represented by microorganisms, plants and animals, as well as to their secondary structure, their biosynthesis and their mechanism of action. They find application in different fields such as agriculture, food industry and medicine, on which we focused our attention in this review. Particularly, we examined AMP potential applicability in wound healing, skin infections and metabolic syndrome, considering their ability to act as potential Angiotensin-Converting Enzyme I and pancreatic lipase inhibitory peptides as well as antioxidant peptides. Moreover, we argued about the pharmacokinetic and pharmacodynamic approaches to develop new antibiotics, the drug development strategies and the formulation approaches which need to be taken into account in developing clinically suitable AMP applications.

Mechanisms of antibiotic action shape the fitness landscapes of resistance mutations

2020 ◽  
Author(s):  
Colin Hemez ◽  
Fabrizio Clarelli ◽  
Adam C. Palmer ◽  
Leonid Chindelevitch ◽  
Theodore Cohen ◽  
...  
Keyword(s):  
New Drugs ◽  
Resistant Bacteria ◽  
Resistance Mutations ◽  
Antibiotic Resistant ◽  
Resistance Selection ◽  
Drug Mechanism ◽  
Selection Window ◽  
Drug Doses ◽  
Target Binding ◽  
Emergence Of Resistance

AbstractAntibiotic-resistant pathogens are a major public health threat. Understanding how an antibiotic’s mechanism of action influences the emergence of resistance could help to improve the design of new drugs and to preserve the effectiveness of existing ones. To this end, we developed a model that links bacterial population dynamics with antibiotic-target binding kinetics. Our approach allows us to derive mechanistic insights on drug activity from population-scale experimental data and to quantify the interplay between drug mechanism and resistance selection. We find that whether a drug acts as a bacteriostatic or bactericidal agent has little influence on resistance selection. We also show that heterogeneous drug-target binding within a population enables antibiotic-resistant bacteria to evolve secondary mutations, even when drug doses remain above the resistant strain’s minimum inhibitory concentration. Our work suggests that antibiotic doses beyond this “secondary mutation selection window” could safeguard against the emergence of high-fitness resistant strains during treatment.

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