scholarly journals Synergism of a Novel 1,2,4-oxadiazole-containing Derivative with Oxacillin against Methicillin-Resistant Staphylococcus aureus

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1258
Author(s):  
Elisabetta Buommino ◽  
Simona De Marino ◽  
Martina Sciarretta ◽  
Marialuisa Piccolo ◽  
Carmen Festa ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Therapeutic Potential ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Vast Number ◽  
Methicillin Resistant ◽  
Inappropriate Use ◽  
Expression Of Genes ◽  
Index Value

Staphylococcusaureus is an important opportunistic pathogen that causes many infections in humans and animals. The inappropriate use of antibiotics has favored the diffusion of methicillin-resistant S. aureus (MRSA), nullifying the efforts undertaken in the discovery of antimicrobial agents. Oxadiazole heterocycles represent privileged scaffolds for the development of new drugs because of their unique bioisosteric properties, easy synthesis, and therapeutic potential. A vast number of oxadiazole-containing derivatives have been discovered as potent antibacterial agents against multidrug-resistant MRSA strains. Here, we investigate the ability of a new library of oxadiazoles to contrast the growth of Gram-positive and Gram-negative strains. The strongest antimicrobial activity was obtained with compounds 3 (4 µM) and 12 (2 µM). Compound 12, selected for further evaluation, was found to be noncytotoxic on the HaCaT cell line up to 25 µM, bactericidal, and was able to improve the activity of oxacillin against the MRSA. The highest synergistic interaction was obtained with the combination values of 0.78 μM for compound 12, and 0.06 μg/mL for oxacillin. The FIC index value of 0.396 confirms the synergistic effect of compound 12 and oxacillin. MRSA treatment with compound 12 reduced the expression of genes included in the mec operon. In conclusion, 12 inhibited the growth of the MRSA and restored the activity of oxacillin, thus resulting in a promising compound in the treatment of MRSA infection.

scholarly journals Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Sirijan Santajit ◽  
Nitaya Indrawattana
Keyword(s):  
Public Health ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Global Public Health ◽  
Drug Usage ◽  
Inappropriate Use ◽  
Public Health Challenges ◽  
Eskape Pathogens

The ESKAPE pathogens (Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa, andEnterobacterspecies) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens.

scholarly journals F-type Pyocins are Diverse Non-Contractile Phage Tail-Like Weapons for Killing Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Senjuti Saha ◽  
Chidozie D. Ojobor ◽  
Erik Mackinnon ◽  
Olesia I. North ◽  
Joseph Bondy-Denomy ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bactericidal Activity ◽  
Pathogenic Bacteria ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Antibiotic Resistant ◽  
Genes Encoding ◽  
Intraspecies Competition

ABSTRACTMost Pseudomonas aeruginosa strains produce bacteriocins derived from contractile or non-contractile phage tails known as R-type and F-type pyocins, respectively. These bacteriocins possess strain-specific bactericidal activity against P. aeruginosa and likely increase evolutionary fitness through intraspecies competition. R-type pyocins have been studied extensively and show promise as alternatives to antibiotics. Although they have similar therapeutic potential, experimental studies on F-type pyocins are limited. Here, we provide a bioinformatic and experimental investigation of F-type pyocins. We introduce a systematic naming scheme for genes found in R- and F-type pyocin operons and identify 15 genes invariably found in strains producing F-type pyocins. Five proteins encoded at the 3’-end of the F-type pyocin cluster are divergent in sequence, and likely determine bactericidal specificity. We use sequence similarities among these proteins to define 11 distinct F-type pyocin groups, five of which had not been previously described. The five genes encoding the variable proteins associate in two modules that have clearly re-assorted independently during the evolution of these operons. These proteins are considerably more diverse than the specificity-determining tail fibers of R-type pyocins, suggesting that F-type pyocins emerged earlier or have been subject to distinct evolutionary pressures. Experimental studies on six F-type pyocin groups show that each displays a distinct spectrum of bactericidal activity. This activity is strongly influenced by the lipopolysaccharide O-antigen type, but other factors also play a role. F-type pyocins appear to kill as efficiently as R-type pyocins. These studies set the stage for the development of F-type pyocins as anti-bacterial therapeutics.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen that causes a broad spectrum of antibiotic resistant infections with high mortality rates, particularly in immunocompromised individuals and cystic fibrosis patients. Due to the increasing frequency of multidrug-resistant P. aeruginosa infections, there is great interest in the development of alternative therapeutics. One alternative is protein-based antimicrobials called bacteriocins, which are produced by one strain of bacteria to kill other strains. In this study, we investigate F-type pyocins, bacteriocins naturally produced by P. aeruginosa that resemble non-contractile phage tails. We show that they are potent killers of P. aeruginosa, and distinct pyocin groups display different killing specificities. We have identified the probable specificity determinants of F-type pyocins, which opens up the potential to engineer them to precisely target strains of pathogenic bacteria. The resemblance of F-type pyocins to well characterized phage tails will greatly facilitate their development into effective antibacterials.

scholarly journals Novel Antibiotic Combinations of Diverse Subclasses for Effective Suppression of Extensively Drug-Resistant Methicillin-Resistant Staphylococcus aureus (MRSA)

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Shumyila Nasir ◽  
Muhammad Sufyan Vohra ◽  
Danish Gul ◽  
Umm E Swaiba ◽  
Maira Aleem ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clavulanic Acid ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Methicillin Resistant ◽  
Development Of Resistance ◽  
Amoxicillin Clavulanic Acid ◽  
Combination Antibiotics ◽  
Time Kill

The emergence of multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), the chief etiological agent for a range of refractory infections, has rendered all β-lactams ineffective against it. The treatment process is further complicated with the development of resistance to glycopeptides, primary antibiotics for treatment of MRSA. Antibiotic combination therapy with existing antimicrobial agents may provide an immediate treatment option. Minimum inhibitory concentrations (MICs) of 18 different commercially available antibiotics were determined along with their 90 possible pairwise combinations and 64 triple combinations to filter out 5 best combinations. Time-Kill kinetics of these combinations were then analyzed to find collateral bactericidal combinations which were then tested on other randomly selected MRSA isolates. Among the top 5 combinations including levofloxacin-ceftazidime; amoxicillin/clavulanic acid-tobramycin; amoxicillin/clavulanic acid-cephradine; amoxicillin/clavulanic acid-ofloxacin; and piperacillin/tazobactam-tobramycin, three combinations were found to be collaterally effective. Levofloxacin-ceftazidime acted synergistically in 80% of the tested clinical MRSA isolates. First-line β-lactams of lower generations can be used effectively against MRSA infection when used in combination. Antibiotics other than glycopeptides may still work in combination.

scholarly journals Promising Antibiofilm Agents: Recent Breakthrough against Biofilm Producing Methicillin-Resistant Staphylococcus aureus

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 667 ◽  
Author(s):  
Marwa I. Abd El-Hamid ◽  
El-sayed Y. El-Naenaeey ◽  
Toka M kandeel ◽  
Wael A. H. Hegazy ◽  
Rasha A. Mosbah ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Proteinase K ◽  
Zno Nps ◽  
Methicillin Resistant ◽  
Biofilm Production ◽  
Antibiofilm Agents

Multidrug resistant (MDR) methicillin-resistant Staphylococcus aureus (MRSA) is a superbug pathogen that causes serious diseases. One of the main reasons for the lack of the effectiveness of antibiotic therapy against infections caused by this resistant pathogen is the recalcitrant nature of MRSA biofilms, which results in an increasingly serious situation worldwide. Consequently, the development of innovative biofilm inhibitors is urgently needed to control the biofilm formation by this pathogen. In this work, we thus sought to evaluate the biofilm inhibiting ability of some promising antibiofilm agents such as zinc oxide nanoparticles (Zno NPs), proteinase K, and hamamelitannin (HAM) in managing the MRSA biofilms. Different phenotypic and genotypic methods were used to identify the biofilm producing MDR MRSA isolates and the antibiofilm/antimicrobial activities of the used promising agents. Our study demonstrated strong antibiofilm activities of ZnO NPs, proteinase K, and HAM against MRSA biofilms along with their transcriptional modulation of biofilm (intercellular adhesion A, icaA) and quorum sensing (QS) (agr) genes. Interestingly, only ZnO NPs showed a powerful antimicrobial activity against this pathogen. Collectively, we observed overall positive correlations between the biofilm production and the antimicrobial resistance/agr genotypes II and IV. Meanwhile, there was no significant correlation between the toxin genes and the biofilm production. The ZnO NPs were recommended to be used alone as potent antimicrobial and antibiofilm agents against MDR MRSA and their biofilm-associated diseases. On the other hand, proteinase-K and HAM can be co-administrated with other antimicrobial agents to manage such types of infections.

scholarly journals Multifunctional Therapeutic Potential of Phytocomplexes and Natural Extracts for Antimicrobial Properties

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1076
Author(s):  
Md. Mominur Rahman ◽  
Md. Saidur Rahaman ◽  
Md. Rezaul Islam ◽  
Md. Emon Hossain ◽  
Faria Mannan Mithi ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Therapeutic Potential ◽  
Antimicrobial Properties ◽  
Antimicrobial Activities ◽  
New Drugs ◽  
Animal Origin ◽  
Multiple Drug ◽  
Common Source ◽  
Phagocytic Cells ◽  
Natural Extracts

Natural products have been known for their antimicrobial factors since time immemorial. Infectious diseases are a worldwide burden that have been deteriorating because of the improvement of species impervious to various anti-infection agents. Hence, the distinguishing proof of antimicrobial specialists with high-power dynamic against MDR microorganisms is central to conquer this issue. Successful treatment of infection involves the improvement of new drugs or some common source of novel medications. Numerous naturally occurring antimicrobial agents can be of plant origin, animal origin, microbial origin, etc. Many plant and animal products have antimicrobial activities due to various active principles, secondary metabolites, or phytochemicals like alkaloids, tannins, terpenoids, essential oils, flavonoids, lectins, phagocytic cells, and many other organic constituents. Phytocomplexes’ antimicrobial movement frequently results from a few particles acting in cooperative energy, and the clinical impacts might be because of the direct effects against microorganisms. The restorative plants that may furnish novel medication lead the antimicrobial movement. The purpose of this study is to investigate the antimicrobial properties of the phytocomplexes and natural extracts of the plants that are ordinarily being utilized as conventional medications and then recommended the chance of utilizing them in drugs for the treatment of multiple drug-resistant disease.

scholarly journals Livestock-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) in Purulent Subcutaneous Lesions of Farm Rabbits

Foods ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 439 ◽  
Author(s):  
Vanessa Silva ◽  
Telma de Sousa ◽  
Paula Gómez ◽  
Carolina Sabença ◽  
Madalena Vieira-Pinto ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Spa Typing ◽  
Disk Diffusion Method ◽  
Methicillin Resistant ◽  
Resistance To Penicillin ◽  
Mrsa Strains

Methicillin-resistant Staphylococcus aureus (MRSA) are one of the main pathogens associated with purulent infections. MRSA clonal complex 97 (CC97) has been identified in a wide diversity of livestock animals. Therefore, we aimed to investigate the antibiotic resistance profiles of MRSA strains isolated from purulent lesions of food-producing rabbits. Samples from purulent lesions of 66 rabbits were collected in a slaughterhouse in Portugal. Samples were seeded onto ORSAB plates with 2 mg/L of oxacillin for MRSA isolation. Susceptibility to antibiotics was tested by the disk diffusion method against 14 antimicrobial agents. The presence of resistance genes, virulence factors and the immune evasion cluster (IEC) system was studied by polymerase chain reaction. All isolates were characterized by multilocus sequence typing (MLST), agr and spa typing. From the 66 samples analyzed, 16 (24.2%) MRSA were detected. All strains were classified as multidrug-resistant as they were resistant to at least three classes of antibiotics. All isolates showed resistance to penicillin, erythromycin and clindamycin. Seven isolates were resistant to gentamicin and harbored the aac(6′)-Ie-aph (2″)-Ia gene. Resistance to tetracycline was detected in 10 isolates harboring the tet(K) gene. The IEC genes were detected in three isolates. MRSA strains belonged to CC97, CC1, CC5, CC15 or CC22. The isolates were assigned to six different spa types. In this study we found a moderate prevalence of multidrug-resistant MRSA strains in food-producing rabbits. This may represent concern for food safety and public health, since cross-contamination may occur, leading to the spread of MRSA and, eventually, the possibility of ingestion of contaminated meat.

Oxazolidinone-containing Hybrids with Antibacterial Activity Against Methicillin-resistant Staphylococcus aureus (MRSA): A Mini-review

2020 ◽  
Vol 20 ◽  
Author(s):  
Dan Jiang ◽  
Bi Liu ◽  
Tao Gao
Keyword(s):  
Staphylococcus Aureus ◽  
Side Effects ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
High Efficiency ◽  
Multidrug Resistant ◽  
Methicillin Resistant ◽  
Wide Range ◽  
Clinically Significant ◽  
Set Up

: The increasing danger by methicillin-resistant Staphylococcus aureus (MRSA) and the limited therapeutic op-tions towards invasive MRSA infections make an urgent demand for the development of novel anti-MRSA agents. Oxazol-idinone derivatives could inhibit protein synthesis by acting on the ribosomal 50S subunit of the bacteria and prevent for-mation of a functional 70S initiation complex, so oxazolidinones are a novel class of antimicrobial agents with potential activity against a wide range of clinically significant multidrug-resistant Gram-positive pathogens. However, oxazolidinones such as linezolid are associated with significant adverse events, and myelosuppression represents the main unfavorable side effects. Moreover, MRSA isolates which are resistant to oxazolidinones have already emerged. Hybridization of oxazoli-dinone with other antibacterial pharmacophores has the potential to interact with multiple targets or to counterbalance the known side effects associated with each pharmacophore. Thus, oxazolidinone-containing hybrids are useful scaffolds for the development of novel anti-MRSA agents. This review covers the recent advances of oxazolidinone-containing hybrids with anti-MRSA activity developed in last decade to set up the direction for the design and development of oxazolidinone-containing hybrids with high efficiency and low toxicity.

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 Symbiotic Plant Peptides EliminateCandida albicansBothIn Vitroand in an Epithelial Infection Model and Inhibit the Proliferation of Immortalized Human Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Lilla Ördögh ◽  
Andrea Vörös ◽  
István Nagy ◽  
Éva Kondorosi ◽  
Attila Kereszt
Keyword(s):  
Fungal Pathogens ◽  
Antimicrobial Agents ◽  
Therapeutic Potential ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Infection Model ◽  
Small Nodule ◽  
Coculture Model ◽  
Epithelial Cell Death

The increasing number of multidrug-resistant microbes now emerging necessitates the identification of novel antimicrobial agents. Plants produce a great variety of antimicrobial peptides including hundreds of small, nodule-specific cysteine-rich NCR peptides that, in the legumeMedicago truncatula, govern the differentiation of endosymbiotic nitrogen fixing bacteria and,in vitro, can display potent antibacterial activities. In this study, the potential candidacidal activity of 19 NCR peptides was investigated. Cationic NCR peptides having an isoelectric point above 9 were efficient in killingCandida albicans, one of the most common fungal pathogens of humans. None of the tested NCR peptides were toxic for immortalized human epithelial cells at concentrations that effectively killed the fungus; however, at higher concentrations, some of them inhibited the division of the cells. Furthermore, the cationic peptides successfully inhibitedC. albicansinduced human epithelial cell death in anin vitrococulture model. These results highlight the therapeutic potential of cationic NCR peptides in the treatment of candidiasis.

scholarly journals Phage sensitivity profiles of a nasopharyngeal opportunistic pathogen in Streptococcus pneumoniae carrier children with recurrent respiratory infections

2020 ◽  
Vol 101 (3) ◽  
pp. 330-336
Author(s):  
L T Bayazitova ◽  
O F Tupkina ◽  
T A Chazova ◽  
N S Konyshev ◽  
K N Syuzev ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Antimicrobial Agents ◽  
Respiratory Infections ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Candida Spp ◽  
Microbial Identification ◽  
Phage Titer ◽  
Recurrent Respiratory Infections ◽  
Staphylococcus Spp

Aim. To study the nature of microbiota and estimating the susceptibility to antibiotics and bacteriophages of conditionally pathogenic microflora of the nasopharynx in children-pneumococcal carriers with recurrent respiratory infections. Methods. Researching microflora was conducted in 182 pneumococcal carriers receiving help in Kazan Scientific and Research Institute of Epidemiology and Microbiology. Microbial identification, testing of susceptibility to antibiotics and bacteriophages was carried out following the regulatory documentation. Bacterial isolates were confirmed by mass spectrometry. The phage titer was determined by the method of agar layers according to Grazia. Results. Nasopharyngeal S. pneumoniae species was presented by Staphylococcus spp., Moraxella spp., Haemophilus spp., Corynebacterium spp., Klebsiella spp and Candida spp. The antimicrobial resistance profiles of Streptococcus pneumoniae: resistant to oxacillin was detected in 20.7% of strains, to erythromycin in 45.9%, to clindamycin in 20%, to trimethoprim-sulfamethoxazole in 18.4%. 19.6% of isolates were multidrug-resistant (MDR, resistant to 3 or more antimicrobial agents). Phage susceptibility test of S. pneumoniaе showed that 97.2% of isolates were resistant to streptococcal bacteriophage, 75% to pyobacteriophage. All antibiotic-resistant strains remained susceptible to Streptococcus phages. The phage titer of Klebsiella in agreement with Grazia method of Kl. pneumoniae ranged from 9106 to 5105 PFU/mL. The ranking results of activities of antistaphylococcal antibiotics (effectiveness descending): fusidic acid mupirocin chloramphenicol cyprofloxacin erythromycin. Conclusion. Nasopharyngeal microbiota of pneumococci carriers children is represented by a variable polymicrobial association; nasopharyngeal strains are effectively lysed by bacteriophages; mono- and polyvalent bacteriophages can be used as an alternative to antibacterial treatment in Streptococcus pneumoniae carriers children with recurrent respiratory infections.

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