scholarly journals Staphylococcus aureus biofilm and the role of bacteriophages in its eradication

2018 ◽  
Vol 72 ◽  
pp. 101-107
Author(s):  
Natalia Łubowska ◽  
Lidia Piechowicz
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Methicillin Resistance ◽  
Therapeutic Option ◽  
Resistant Bacteria ◽  
Prosthetic Heart Valves ◽  
Biofilm Structure ◽  
Implanted Devices

The ability to form biofilm is an important virulence factor of many microorganisms. Infections involving biofilms account for approx. 65% of all human infections. Biofilms may develop on intravascular catheters or implanted devices such as prosthetic heart valves. Implanted devices are covered by biofilm and become reservoirs of microorganisms which can be a cause of persistent infections (endocarditis, deep tissue abscesses, septic arthritis, and osteomyelitis). Treatment of infections caused by biofilm-growing cells is linked to a high risk of failure due to an extreme resistance to antimicrobial agents and increased capacity to evade the immune responses. A large number of biofilm-associated infections involve Staphylococcus aureus. Treatment of staphylococcal infections is a great challenge for clinicians because of the presence of various mechanisms of resistance to antibiotics in S. aureus, for example methicillin resistance and biofilm production. Therapeutic difficulties related with antibiotic-resistant bacteria and limitations in research on new antimicrobials were the reasons that nearly 100 years after discovery, bacteriophages caught the attention of scientists around the world as a new therapeutic option for bacterial infections. Numerous in vitro studies on S. aureus strains showed that phages can both prevent biofilm formation and contribute to the elimination of bacteria from the mature biofilm structure. The major role in biofilm eradication play depolymerases produced by some phages which facilitate their penetration into the inner layers of biofilm by disturbing the biofilm structure. This leads to the conclusion that bacteriophages treatment might become a new strategy in the prevention and eradication of infectious bacterial biofilms, including these formed by S. aureus.

scholarly journals Design, Overproduction and Purification of the Chimeric Phage Lysin MLTphg Fighting against Staphylococcus aureus

Processes ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 1587
Author(s):  
Feng Wang ◽  
Xiaohang Liu ◽  
Zhengyu Deng ◽  
Yao Zhang ◽  
Xinyu Ji ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Conventional Antibiotics ◽  
Phage Lysin ◽  
Shed Light

With the increasing spread of multidrug-resistant bacterial pathogens, it is of great importance to develop alternatives to conventional antibiotics. Here, we report the generation of a chimeric phage lysin, MLTphg, which was assembled by joining the lysins derived from Meiothermus bacteriophage MMP7 and Thermus bacteriophage TSP4 with a flexible linker via chimeolysin engineering. As a potential antimicrobial agent, MLTphg can be obtained by overproduction in Escherichia coli BL21(DE3) cells and the following Ni-affinity chromatography. Finally, we recovered about 40 ± 1.9 mg of MLTphg from 1 L of the host E. coli BL21(DE3) culture. The purified MLTphg showed peak activity against Staphylococcus aureus ATCC6538 between 35 and 40 °C, and maintained approximately 44.5 ± 2.1% activity at room temperature (25 °C). Moreover, as a produced chimera, it exhibited considerably improved bactericidal activity against Staphylococcus aureus (2.9 ± 0.1 log10 reduction was observed upon 40 nM MLTphg treatment at 37 °C for 30 min) and also a group of antibiotic-resistant bacteria compared to its parental lysins, TSPphg and MMPphg. In the current age of growing antibiotic resistance, our results provide an engineering basis for developing phage lysins as novel antimicrobial agents and shed light on bacteriophage-based strategies to tackle bacterial infections.

scholarly journals In Vitro Activities of 28 Antimicrobial Agents against Staphylococcus aureus Isolates from Tertiary-Care Hospitals in Korea: a Nationwide Survey

2004 ◽  
Vol 48 (4) ◽  
pp. 1124-1127 ◽  
Author(s):  
Hong Bin Kim ◽  
Hee-Chang Jang ◽  
Hee Jung Nam ◽  
Yeong Seon Lee ◽  
Bong Su Kim ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Methicillin Resistance ◽  
Tertiary Care ◽  
Nationwide Survey ◽  
Resistance Rate ◽  
Current Status ◽  
Diffusion Method ◽  
Disk Diffusion Method

ABSTRACT Staphylococcus aureus, one of the most frequently isolated pathogens in both hospitals and the community, has been particularly efficient at developing resistance to antimicrobial agents. As methicillin-resistant S. aureus (MRSA) has prevailed and, furthermore, as S. aureus with reduced susceptibility to vancomycin has emerged, the therapeutic options for the treatment of S. aureus infections have become limited. To update the current status of antibiotic resistance, clinical S. aureus isolates were collected from eight university-affiliated hospitals from June 1999 to January 2001. Susceptibility tests with 28 antibiotics were performed by the disk diffusion method. Among a total of 682 isolates, the methicillin resistance rate was 64% (439 of 682), and most of the MRSA isolates were resistant to multiple classes of antibiotics. Although a constitutive macrolide-lincosamide-streptogramin B resistance phenotype was common, no isolates were resistant to quinupristin-dalfopristin or linezolid. Rifampin, fusidic acid, trimethoprim-sulfamethoxazole, and arbekacin showed superior in vitro activity compared with the other antibiotics against the MRSA isolates. No isolates showed reduced susceptibility to vancomycin.

scholarly journals Pharmacodynamic Functions of Synthetic Derivatives for Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Mojdeh Dinarvand ◽  
Malcolm P. Spain ◽  
Fatemeh Vafaee
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Mycobacterium Tuberculosis ◽  
Antimicrobial Agents ◽  
Resistant Bacteria ◽  
Synthetic Compounds ◽  
Methicillin Resistant ◽  
Chemical Structures ◽  
Time Kill

Drug resistant bacteria have emerged, so robust methods are needed to evaluate combined activities of known antibiotics as well as new synthetic compounds as novel antimicrobial agents to treatment efficacy in severe bacterial infections. Marine natural products (MNPs) have become new strong leads in the drug discovery endeavor and an effective alternative to control infections. Herein, we report the bioassay guided fractionation of marine extracts from the sponges Lendenfeldia, Ircinia, and Dysidea that led us to identify novel compounds with antimicrobial properties. Chemical synthesis of predicted compounds and their analogs has confirmed that the proposed structures may encode novel chemical structures with promising antimicrobial activity against the medically important pathogens. Several of the synthetic analogs exhibited potent and broad spectrum in vitro antibacterial activity, especially against the Methicillin-resistant Staphylococcus aureus (MRSA) (MICs to 12.5 μM), Mycobacterium tuberculosis (MICs to 0.02 μM), uropathogenic Escherichia coli (MIC o 6.2 μM), and Pseudomonas aeruginosa (MIC to 3.1 μM). Checkerboard assay (CA) and time-kill studies (TKS) experiments analyzed with the a pharmacodynamic model, have potentials for in vitro evaluation of new and existing antimicrobials. In this study, CA and TKS were used to identify the potential benefits of an antibiotic combination (i.e., synthetic compounds, vancomycin, and rifampicin) for the treatment of MRSA and M. tuberculosis infections. CA experiments indicated that the association of compounds 1a and 2a with vancomycin and compound 3 with rifampicin combination have a synergistic effect against a MRSA and M. tuberculosis infections, respectively. Furthermore, the analysis of TKS uncovered bactericidal and time-dependent properties of the synthetic compounds that may be due to variations in hydrophobicity and mechanisms of action of the molecules tested. The results of cross-referencing antimicrobial activity, and toxicity, CA, and Time-Kill experiments establish that these synthetic compounds are promising potential leads, with a favorable therapeutic index for antimicrobial drug development.

scholarly journals Synergistic Effect of the Combination of Commercial Essential Oils with Standard Antibiotics: In vitro Evaluation

2020 ◽  
Vol 63 (3) ◽  
pp. 242-252
Author(s):  
Aneela Mehboob ◽  
Tanveer Abbas
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Essential Oils ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Nigella Sativa ◽  
Citrus Limon ◽  
Bacterial Strains ◽  
Lavandula Angustifolia

The aim of this investigation was to determine the antibacterial activity of essential oils and  to assess the outcomes produced by the combinations of antibiotics and essential oils. To execute this research, gold standard and conventional methods were used. Antibacterial potency of five essential oils namely Citrus limon, Elettaria cardamomum, Lavandula angustifolia, Nigella sativa and Prunus dulcis were tested against Escherichia coli, Serratia fonticola, Serratia liquefaciens, Citrobacter freundii and Staphylococcus aureus recouped from street foods of Karachi. Among five of them, Citrus limon and Lavandula angustifolia were the most potent essential oils showing highest antibacterial activity in their undiluted form with the exception of Staphylococcus aureus but their mix at different concentrations successfully inhibited the growth of Staphylococcus aureus and Serratia fonticola. Synergistic outcomes were achieved against all the tested bacterial strains from the mix of essential oils and antibiotics, however antagonistic results were also obtained. This exploration underpins the application of essential oils alone and in combinations with antimicrobial agents to improve the affectability of ineffective drugs and aides in the advancement of new antimicrobial drugs to treat bacterial infections utilizing therapeutic plants.    

scholarly journals Antibacterial Activity of Honey against Methicillin-Resistant Staphylococcus aureus: A Laboratory-Based Experimental Study

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammedaman Mama ◽  
Teklu Teshome ◽  
Jafer Detamo
Keyword(s):  
Staphylococcus Aureus ◽  
Experimental Study ◽  
Antibacterial Activity ◽  
Wound Infection ◽  
Antimicrobial Agents ◽  
Methicillin Resistance ◽  
Methicillin Resistant ◽  
Antimicrobial Drug Resistance ◽  
In Vitro Antibacterial Activity

Background. Antimicrobial drug resistance is one of the serious issues this world is facing nowadays, and increased cost of searching for effective antimicrobial agents and the decreased rate of new drug discovery have made the situation increasingly worrisome. Objective. The aim of this study is to determine in vitro antibacterial activity of honey against methicillin-resistant Staphylococcus aureus isolates from wound infection. Methods. An experimental study was conducted from May to November 2017. Methicillin resistance was detected using cefoxitin (30 μg) and oxacillin (1 μg) antibiotic discs. Different concentrations of honey (25–100% v/v) were tested against each type of clinical isolates obtained from wound infection. A preliminary sensitivity test was done to all types of honey by using disk diffusion while minimum inhibitory concentration and minimum bactericidal concentration were determined for the most potent honey by the broth dilution technique. All statistical analysis was performed by using Statistical Package for the Social Sciences version 20. Results. In this study, 36 bacterial isolates were recovered from 50 specimens, showing an isolation rate of 72%. The predominant bacteria isolated from the infected wounds were Staphylococcus aureus (15, 41.7%). Among identified Staphylococcus aureus, methicillin resistance accounts for 10 isolates (27.8%). All isolates showed a high frequency of resistance to tetracycline. Four collected honey varieties exhibited antibacterial activity, while the strongest inhibitory activity was demonstrated by honey-2 at 75% v/v. The mean MIC and MBC of honey-2 ranged from 9.38 to 37.5% v/v. Conclusions. Tested honey has both a bacteriostatic and bactericidal activity. Among the tested honey, “honey-2” had high antibacterial potency than others.

scholarly journals Prevalence and Antibiotics Susceptibility Pattern of Urine Bacterial Isolates from Tripoli Medical Center (TMC), Tripoli, Libya

2021 ◽  
Vol 3 (3) ◽  
pp. 221-226
Author(s):  
Abir Ben Ashur ◽  
◽  
Hamida El Magrahi ◽  
Asma Elkammoshi ◽  
Hiba Alsharif ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antimicrobial Susceptibility ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Bacterial Pathogens ◽  
Diffusion Method ◽  
Resistant Bacteria ◽  
Klebsiella Pneumonia ◽  
Tract Infections

Introduction: Urinary tract infections (UTI) are one of the most common human bacterial infections encountered by physicians. The risk of resistant microbes is emerging as a result of the overuse of antibiotics treatments. The presence of pathogens with increased resistance to antimicrobial agents makes UTIs difficult to treat. This study was aimed at determining the prevalence of the pathogens that cause UTIs, as well as the antibiotic susceptibility of these isolates. Materials and methods: This prospective study was conducted from February 2020 to April 2020; a total number of 200 urine samples were collected from patients who daily attended TMC Libya. Bacterial pathogens were determined by bacteriological culture methods and Antimicrobial susceptibility testing was done by using the disc diffusion method. Results: Out of 200 samples, 110 cases had a positive culture. The dominant bacterial pathogens were Gram-negative that being with Escherichia coli (49, 55.68%), followed by Klebsiella pneumonia (18, 20.46%), Pseudomona aeruginosa (9, 10.23%), Proteus mirabilis (8, 9.09%), Enterobacter aerogenes (2, 2.27%), Citrobacter freundii (2, 2.27%). Gram-positive bacteria were Staphylococcus aureus 20 (90.91%) followed by S. saprophyticus (2, 9.01%) of the isolate’s strains. The isolated uropathogen showed increased levels of resistance to antibiotics. Where the Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus indicated the highest antibiotic resistance to Nitrofurantoin, Sulfamethoxazole/trimethoprim, Tetracycline, Ciprofloxacin, Metronidazole and also revealed the most sensitivity to Cefixime followed by doxycycline and ceftriaxone. Conclusions: The obtained results emphasized the emergence of highly resistant bacteria to most of the tested antimicrobials and propose the need for physicians to change their treatment pattern depending on antimicrobial susceptibility results.

scholarly journals Strategies of Detecting Bacteria Using Fluorescence-Based Dyes

2021 ◽  
Vol 9 ◽  
Author(s):  
Shin A Yoon ◽  
Sun Young Park ◽  
Yujin Cha ◽  
Lavanya Gopala ◽  
Min Hee Lee
Keyword(s):  
Fluorescent Probes ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Detection Methods ◽  
Future Research ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Intracellular Enzyme

Identification of bacterial strains is critical for the theranostics of bacterial infections and the development of antibiotics. Many organic fluorescent probes have been developed to overcome the limitations of conventional detection methods. These probes can detect bacteria with “off-on” fluorescence change, which enables the real-time imaging and quantitative analysis of bacteria in vitro and in vivo. In this review, we outline recent advances in the development of fluorescence-based dyes capable of detecting bacteria. Detection strategies are described, including specific interactions with bacterial cell wall components, bacterial and intracellular enzyme reactions, and peptidoglycan synthesis reactions. These include theranostic probes that allow simultaneous bacterial detection and photodynamic antimicrobial effects. Some examples of other miscellaneous detections in bacteria have also been described. In addition, this review demonstrates the validation of these fluorescent probes using a variety of biological models such as gram-negative and -positive bacteria, antibiotic-resistant bacteria, infected cancer cells, tumor-bearing, and infected mice. Prospects for future research are outlined by presenting the importance of effective in vitro and in vivo detection of bacteria and development of antimicrobial agents.

scholarly journals Comparative in vitro Activities of Different Antibiotics against Clinical Isolates of Gram-negative Bacilli

2019 ◽  
pp. 1-8
Author(s):  
Sachin H. Jain ◽  
Pradnya Joshi
Keyword(s):  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Therapeutic Option ◽  
Critical Role ◽  
Final Analysis ◽  
Klebsiella Species ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
E Coli

Objective: The local anti-microbial susceptibility profile plays a very critical role in guiding clinicians to choose the appropriate empiric therapies. This study was conducted to assess the pathogen characteristics and the in vitro susceptibility of different Gram negative isolates to commonly used antibiotics in our hospital settings. Methods: A total of 110 Gram negative isolates were included in the study.  A retrospective, observational analysis of antibiogram data was performed for four antimicrobial agents including CSE-1034 (ceftriaxone-sulbactam-EDTA), piperacillin-tazobactam (pip-taz), cefoperazone-sulbactam and meropenem.  Results: Of the 200 clinical specimens analysed, Gram negative isolates obtained from 110 samples were included in the final analysis. The most common Gram negative isolates were Klebsiella species (35.5%), E. coli (33.6%) and P. aeruginosa (21.8%). The overall susceptibility was highest to CSE-1034 (100%) followed by meropenem (66.4%), cefoperazone-sulbactam (56.4%) and pip-taz (45.5%). The MIC90 range of CSE-1034 for Enterobacteriaceae was ≤0.5-≤4μg/ml and ≤2μg/ml for susceptible P. aeruginosa isolates. The MIC90 of meropenem for 94.4% of meropenem-susceptible Enterobacteriaceae strains was <0.25μg/ml and 64.3% of P. aeruginosa were having MIC ≤0.25μg/ml. The MIC90 of pip-taz for 82.5% of the pip-taz susceptible Enterobacteriaceae strains was 4μg/ml and 63.6% of P. aeruginosa was ≤8.0μg/ml. The MIC90 of cefoperazone-sulbactam susceptible strains were between ≤8 to ≤16μg/ml and 45.8% isolates of susceptible P. aeruginosa were having MIC between ≤8 to ≤16μg/ml. Conclusions: Overall, this in vitro surveillance study suggests that CSE-1034 can be considered an important therapeutic option for the treatment of various multi drug resistant Gram-negative bacterial infections and avert the threat of resistance to last resort antibiotics including carbapenems.

Development of Peptides that Inhibit Aminoglycoside-Modifying Enzymes and β-Lactamases for Control of Resistant Bacteria

2020 ◽  
Vol 21 (10) ◽  
pp. 1011-1026
Author(s):  
Bruna O. Costa ◽  
Marlon H. Cardoso ◽  
Octávio L. Franco
Keyword(s):  
Drug Target ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Strategies ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Specific Chemical ◽  
Target Interaction ◽  
Multiresistant Bacteria ◽  
Acute Bacterial Infections

: Aminoglycosides and β-lactams are the most commonly used antimicrobial agents in clinical practice. This occurs because they are capable of acting in the treatment of acute bacterial infections. However, the effectiveness of antibiotics has been constantly threatened due to bacterial pathogens producing resistance enzymes. Among them, the aminoglycoside-modifying enzymes (AMEs) and β-lactamase enzymes are the most frequently reported resistance mechanisms. AMEs can inactivate aminoglycosides by adding specific chemical molecules in the compound, whereas β-lactamases hydrolyze the β-lactams ring, preventing drug-target interaction. Thus, these enzymes provide a scenario of multidrug-resistance and a significant threat to public health at a global level. In response to this challenge, in recent decades, several studies have focused on the development of inhibitors that can restore aminoglycosides and β-lactams activity. In this context, peptides appear as a promising approach in the field of inhibitors for future antibacterial therapies, as multiresistant bacteria may be susceptible to these molecules. Therefore, this review focused on the most recent findings related to peptide-based inhibitors that act on AMEs and β-lactamases, and how these molecules could be used for future treatment strategies.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

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