scholarly journals OMN6 a novel bioengineered peptide for the treatment of multidrug resistant Gram negative bacteria

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shira Mandel ◽  
Janna Michaeli ◽  
Noa Nur ◽  
Isabelle Erbetti ◽  
Jonathan Zazoun ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Antimicrobial Agents ◽  
Cyclic Peptide ◽  
Safety Margin ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Development Of Resistance ◽  
Cecropin A

AbstractNew antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.

scholarly journals Reversion of antibiotic resistance in multidrug-resistant pathogens using non-antibiotic pharmaceutical benzydamine

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yuan Liu ◽  
Ziwen Tong ◽  
Jingru Shi ◽  
Yuqian Jia ◽  
Tian Deng ◽  
...  
Keyword(s):  
Cost Effective ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Treatment Regimens ◽  
Development Of Resistance ◽  
Metabolic States ◽  
Animal Infection ◽  
Life Threatening

AbstractAntimicrobial resistance has been a growing concern that gradually undermines our tradition treatment regimens. The fact that few antibacterial drugs with new scaffolds or targets have been approved in the past two decades aggravates this crisis. Repurposing drugs as potent antibiotic adjuvants offers a cost-effective strategy to mitigate the development of resistance and tackle the increasing infections by multidrug-resistant (MDR) bacteria. Herein, we found that benzydamine, a widely used non‐steroidal anti‐inflammatory drug in clinic, remarkably potentiated broad-spectrum antibiotic-tetracyclines activity against a panel of clinically important pathogens, including MRSA, VRE, MCRPEC and tet(X)-positive Gram-negative bacteria. Mechanistic studies showed that benzydamine dissipated membrane potential (▵Ψ) in both Gram-positive and Gram-negative bacteria, which in turn upregulated the transmembrane proton gradient (▵pH) and promoted the uptake of tetracyclines. Additionally, benzydamine exacerbated the oxidative stress by triggering the production of ROS and suppressing GAD system-mediated oxidative defensive. This mode of action explains the great bactericidal activity of the doxycycline-benzydamine combination against different metabolic states of bacteria involve persister cells. As a proof-of-concept, the in vivo efficacy of this drug combination was evidenced in multiple animal infection models. These findings indicate that benzydamine is a potential tetracyclines adjuvant to address life-threatening infections by MDR bacteria.

scholarly journals Metal-Based Nanoparticles as Antimicrobial Agents: An Overview

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 292 ◽  
Author(s):  
Elena Sánchez-López ◽  
Daniela Gomes ◽  
Gerard Esteruelas ◽  
Lorena Bonilla ◽  
Ana Laura Lopez-Machado ◽  
...  
Keyword(s):  
Metal Nanoparticles ◽  
Antimicrobial Agents ◽  
Physicochemical Characterization ◽  
Copper Oxide Nanoparticles ◽  
Added Value ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Development Of Resistance ◽  
Different Types

Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while others (e.g., gold, zinc oxide, copper, and copper oxide nanoparticles) commonly used in antibiotherapy are also reviewed. The novelty of this review relies on the comparative discussion of the different types of metal nanoparticles, their production methods, physicochemical characterization, and pharmacokinetics together with the toxicological risk encountered with the use of different types of nanoparticles as antimicrobial agents. Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted.

scholarly journals Bacteriocins, Antimicrobial Peptides from Bacterial Origin: Overview of Their Biology and Their Impact against Multidrug-Resistant Bacteria

2020 ◽  
Vol 8 (5) ◽  
pp. 639 ◽  
Author(s):  
Alexis Simons ◽  
Kamel Alhanout ◽  
Raphaël E. Duval
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Further Development

Currently, the emergence and ongoing dissemination of antimicrobial resistance among bacteria are critical health and economic issue, leading to increased rates of morbidity and mortality related to bacterial infections. Research and development for new antimicrobial agents is currently needed to overcome this problem. Among the different approaches studied, bacteriocins seem to be a promising possibility. These molecules are peptides naturally synthesized by ribosomes, produced by both Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), which will allow these bacteriocin producers to survive in highly competitive polymicrobial environment. Bacteriocins exhibit antimicrobial activity with variable spectrum depending on the peptide, which may target several bacteria. Already used in some areas such as agro-food, bacteriocins may be considered as interesting candidates for further development as antimicrobial agents used in health contexts, particularly considering the issue of antimicrobial resistance. The aim of this review is to present an updated global report on the biology of bacteriocins produced by GPB and GNB, as well as their antibacterial activity against relevant bacterial pathogens, and especially against multidrug-resistant bacteria.

scholarly journals Peptidomic Analysis of Skin Secretions of the Caribbean Frogs Leptodactylus insularum and Leptodactylus nesiotus (Leptodactylidae) Identifies an Ocellatin with Broad Spectrum Antimicrobial Activity

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 718 ◽  
Author(s):  
Gervonne Barran ◽  
Jolanta Kolodziejek ◽  
Laurent Coquet ◽  
Jérôme Leprince ◽  
Thierry Jouenne ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Broad Spectrum ◽  
Antimicrobial Agents ◽  
Therapeutic Potential ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Peptidomic Analysis ◽  
Skin Secretions ◽  
Long Acting

Ocellatins are peptides produced in the skins of frogs belonging to the genus Leptodactylus that generally display weak antimicrobial activity against Gram-negative bacteria only. Peptidomic analysis of norepinephrine-stimulated skin secretions from Leptodactylus insularum Barbour 1906 and Leptodactylus nesiotus Heyer 1994, collected in the Icacos Peninsula, Trinidad, led to the purification and structural characterization of five ocellatin-related peptides from L. insularum (ocellatin-1I together with its (1–16) fragment, ocellatin-2I and its (1–16) fragment, and ocellatin-3I) and four ocellatins from L. nesiotus (ocellatin-1N, -2N, -3N, and -4N). While ocellatins-1I, -2I, and -1N showed a typically low antimicrobial potency against Gram-negative bacteria, ocellatin-3N (GIFDVLKNLAKGVITSLAS.NH2) was active against an antibiotic-resistant strain of Klebsiella pneumoniae and reference strains of Escherichia coli, K. pneumoniae, Pseudomonas aeruginosa, and Salmonella typhimurium (minimum inhibitory concentrations (MICs) in the range 31.25–62.5 μM), and was the only peptide active against Gram-positive Staphylococcus aureus (MIC = 31.25 μM) and Enterococcus faecium (MIC = 62.5 μM). The therapeutic potential of ocellatin-3N is limited by its moderate hemolytic activity (LC50 = 98 μM) against mouse erythrocytes. The peptide represents a template for the design of long-acting, non-toxic, and broad-spectrum antimicrobial agents for targeting multidrug-resistant pathogens.

scholarly journals A Review of Superbug: A Global Threat in Health Care System

2018 ◽  
Vol 4 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Bhuiyan Mohammad Mahtab Uddin ◽  
Md Abdullah Yusuf ◽  
Zubair Ahmed Ratan
Keyword(s):  
Public Health ◽  
Health Problem ◽  
Antimicrobial Agents ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Major Public Health Problem ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Hospital Acquired

The rapid spread and dissemination of the multidrug-resistant bacteria worldwide represents a major public health problem. The development of antibiotics decreased the mortality among the human and animals leading to a better life expectancy. But the injudicious use of antimicrobials and selection pressure the microbes have developed resistance which became more prominent during last few decades. With the evolution of Methicilin-resistant Staphylococcus aureus (MRSA), Hospital-acquired MRSA, Communityacquired MRSA and MDR TB (Multidrug resistant tuberculosis) challenge for the clinicians have increased to a greater extent. The global emergence and dissemination of acquired carbapenemases among gram negative bacteria are considered a major public health problem. Gram-negative bacteria, most notably Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, are among the most important causes of serious hospital-acquired and community-onset bacterial infections in humans, and resistance to antimicrobial agents in these bacteria has become an increasingly relevant problem. Recent development in nanotechnology based drug delivery system may prove to be solution for combating these resistant bacteria. However policies and regulations for antibiotic use should be formulated to control the further development of resistance among the microbes.Bangladesh Journal of Infectious Diseases 2017;4(1):25-28

MULTI-RESISTANT CARBAPENEM-INSENSITIVE GRAMNEGATIVE BACTERIA IN PATIENTS WITH SOLID TUMORS

2017 ◽  
Vol 63 (5) ◽  
pp. 780-784
Author(s):  
Anna Polishchuk ◽  
Yelena Yakubovich ◽  
Viktor Osovskikh ◽  
Vladimir Yevtushenko ◽  
O. Polukhina
Keyword(s):  
Cancer Patients ◽  
Solid Tumors ◽  
Antimicrobial Agents ◽  
Distinct Species ◽  
Multidrug Resistant ◽  
Klebsiella Pneumonia ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Wide Range ◽  
Genes Encoding

Infections caused by multiresistant gram-negative bacteria are one of the major problems in the treatment of cancer patients. Strains with mechanisms of resistance mediated by carbapenemases represent a particular threat since they spread rapidly and are characterized by high frequency of occurrence of multiresistance to antimicrobial agents. Here we show that 14 out of 399 gram-negative bacteria (3,5 %), isolated from clinical specimens of 11 patients with solid tumors (n=581) in a hospital of federal level in January 2015-April 2016 were carbapenem-insusceptible. Among them 3 isolates of Klebsiella pneumonia, 2 Enterobacter cloacae, 2 Pseudomonas aeruginosa and 7 Acinetobacter baumannii. All 14 strains were resistant to a wide range of antimicrobial agents including beta-lactams, aminoglycosides, monobactams and fluoroquinolones. The only antimicrobial agent to which all but one Exloacae strain remained susceptible was colistin. This strain was insusceptible to all 10 antimicrobial agents tested in the study, including tigecycline. We observed two cases of infection of a single patient by 2-3 distinct species of multidrug-resistant gram-negative bacteria. In 79 % of the strains the genes encoding carbapenemases of OXA40/24, KPC, VIM and NDM types were detected. Despite the fact that multidrug-resistant car-bapenem-insusceptible strains of gram-negative bacteria were isolated from a relatively small number of cancer patients, the majority of these strains represent a particular epidemiological and clinical threat.

scholarly journals Gram-Negative Bacteria Holding Together in a Biofilm: The Acinetobacter baumannii Way

2021 ◽  
Vol 9 (7) ◽  
pp. 1353
Author(s):  
Arianna Pompilio ◽  
Daniela Scribano ◽  
Meysam Sarshar ◽  
Giovanni Di Bonaventura ◽  
Anna Teresa Palamara ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Public Health Problem ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Abiotic Surfaces ◽  
Healthcare Associated

Bacterial biofilms are a serious public-health problem worldwide. In recent years, the rates of antibiotic-resistant Gram-negative bacteria associated with biofilm-forming activity have increased worrisomely, particularly among healthcare-associated pathogens. Acinetobacter baumannii is a critically opportunistic pathogen, due to the high rates of antibiotic resistant strains causing healthcare-acquired infections (HAIs). The clinical isolates of A. baumannii can form biofilms on both biotic and abiotic surfaces; hospital settings and medical devices are the ideal environments for A. baumannii biofilms, thereby representing the main source of patient infections. However, the paucity of therapeutic options poses major concerns for human health infections caused by A. baumannii strains. The increasing number of multidrug-resistant A. baumannii biofilm-forming isolates in association with the limited number of biofilm-eradicating treatments intensify the need for effective antibiofilm approaches. This review discusses the mechanisms used by this opportunistic pathogen to form biofilms, describes their clinical impact, and summarizes the current and emerging treatment options available, both to prevent their formation and to disrupt preformed A. baumannii biofilms.

Antibiotic Resistance as a Virulence Factor of Opportunistic Microorganisms

2021 ◽  
pp. 50-56
Author(s):  
NА Gordinskaya ◽  
EV Boriskina ◽  
DV Kryazhev
Keyword(s):  
Antibiotic Resistance ◽  
Infectious Diseases ◽  
Molecular Genetic ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Coagulase Negative Staphylococci ◽  
Genetic Studies ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Resistant Strains

Introduction: A large number of infectious processes are associated with opportunistic microorganisms. The phenotype of antibiotic resistance of such pathogens is multidrug-resistant strains with the presence of various β-lactamases. Our objective was to determine the phenotypic and genotypic features of antibiotic resistance of staphylococci, enterobacteria, and non-fermenting Gram-negative bacteria – the cause of infectious diseases in patients of various health facilities of Nizhny Novgorod. Material and methods: Using classical microbiological methods and molecular genetic studies, we analyzed 486 strains of microorganisms isolated from the upper respiratory tract, intestines, urine, and wound discharge of patients in 2019–2020. In all isolates, the phenotype of antibiotic resistance was determined by the disco-diffusion method (Bioanalyse, Turkey) and using the Multiscan FC spectrophotometer (ThermoScientific, Finland) with Microlatest tablets (PLIVA-Lachema, Czech Republic), along with molecular features of resistance mechanisms by PCR on the CFX96 device (BioRad, USA) using AmpliSens kits (Russia). Results and discussion: The results showed that the most prevalent causative agents of infectious diseases (40.7 %) were Gram-negative bacteria, of which Enterobacteriaceae and non-fermenting bacteria accounted for 27.1 % and 13.6 % of cases, respectively. Staphylococci were isolated in 37.6 % of patients: S. aureus and coagulase-negative staphylococci induced 13.4 % and 24.2 % of cases, respectively. The analysis of antibiotic resistance of the isolates showed a high level of antimicrobial resistance in all hospitals, regardless of the isolation locus. The phenotype of methicillin-resistant strains was found in 26.3 % and 37.9 % of S. aureus and coagulase-negative staphylococci, respectively; the mecA gene was found in 89.0 % of methicillin-resistant staphylococci. The highest number of antibiotic-resistant strains among Gram-negative microorganisms was observed in K. pneumoniae, A. baumannii, and P. aeruginosa. We established that 61.7 % of K. pneumoniae, 75.1 % of A. baumannii, and 58.2 % of P. aeruginosa were resistant to carbapenems. The results of molecular genetic studies confirmed the presence of serine carbapenemases KPC and OXA groups in all multidrug-resistant K. pneumoniae and A. baumannii; genes of the metallo-β-lactamase of VIM group were found in 40.9 % strains of P. aeruginosa. The production of numerous β-lactamases and the presence of determinants of antibiotic resistance in the genome determine the virulent properties of opportunistic microorganisms. Conclusion: The antibiotic resistance of opportunistic microorganisms is the cause of developing a chronic infectious process. Today, a wide spread of antibiotic-resistant infectious agents is a serious public health problem, which determines the need for constant microbiological monitoring and studies of molecular mechanisms of resistance to identify the most potent antibiotics and to determine the ways of eradication of multidrug-resistant strains.

scholarly journals Drugs Repurposing for Multi-Drug Resistant Bacterial Infections

2020 ◽  
Author(s):  
Andrea Vila Domínguez ◽  
Manuel Enrique Jiménez Mejías ◽  
Younes Smani
Keyword(s):  
Antimicrobial Resistance ◽  
Global Health ◽  
Mechanism Of Action ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Therapeutic Potential ◽  
Multidrug Resistant ◽  
Therapeutic Strategies ◽  
Clinical Development ◽  
Gram Negative

Different institutions recognized that antimicrobial resistance is a global health threat that has compounded by the reduction in the discovery and development of new antimicrobial agents. Therefore, the development of new antimicrobial therapeutic strategies requires immediate attention to avoid the 10 million deaths predicted to occur by 2050 as a result of multidrug-resistant (MDR) bacteria. Despite the great interest in the development of repurposing drugs, only few repurposing drugs are under clinical development against Gram-negative critical-priority pathogens. In this chapter, we aim: (i) to discuss the therapeutic potential of the repurposing drugs for treating MDR bacterial infections, (ii) to summarize their mechanism of action, and (iii) to provide an overview for their preclinical and clinical development against these critical-priority pathogens.

scholarly journals Colistin: The phoenix Arises

2006 ◽  
Vol 17 (5) ◽  
pp. 267-269 ◽  
Author(s):  
JM Conly ◽  
BL Johnston
Keyword(s):  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
High Incidence ◽  
The World ◽  
Lung Infections ◽  
Polypeptide Antibiotics ◽  
Ophthalmic Solutions ◽  
The Phoenix

The polymyxins were discovered in the 1940s and represent a group of closely related polypeptide antibiotics obtained fromBacillus polymyxa, which was originally isolated from soil (1,2). Although they have been used extensively worldwide in topical otic and ophthalmic solutions for decades, the intravenous formulations were gradually abandoned in most parts of the world in the early 1980s because of the reported high incidence of nephrotoxicity (3-5). As a result, the use of polymyxin preparations has been mainly restricted to the treatment of lung infections due to multidrug-resistant (MDR) gram-negative bacteria in patients with cystic fibrosis (6,7). The emergence of bacteria resistant to most classes of commercially available antibiotics and the shortage of novel antimicrobial agents with activity against gram-negative microorganisms have led to the reemergence of polymyxins as a valuable addition to the therapeutic armamentarium. It was thus considered timely to review colistin and its emerging role in managing infections due to MDR gram-negative bacteria.

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