scholarly journals Impact of a Novel Anticoccidial Analogue on Systemic Staphylococcus aureus Infection in a Bioluminescent Mouse Model

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 65
Author(s):  
Hang Thi Nguyen ◽  
Henrietta Venter ◽  
Lucy Woolford ◽  
Kelly Young ◽  
Adam McCluskey ◽  
...  

In this study, we investigated the potential of an analogue of robenidine (NCL179) to expand its chemical diversity for the treatment of multidrug-resistant (MDR) bacterial infections. We show that NCL179 exhibits potent bactericidal activity, returning minimum inhibitory concentration/minimum bactericidal concentrations (MICs/MBCs) of 1–2 µg/mL against methicillin-resistant Staphylococcus aureus, MICs/MBCs of 1–2 µg/mL against methicillin-resistant S. pseudintermedius and MICs/MBCs of 2–4 µg/mL against vancomycin-resistant enterococci. NCL179 showed synergistic activity against clinical isolates and reference strains of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa in the presence of sub-inhibitory concentrations of colistin, whereas NCL179 alone had no activity. Mice given oral NCL179 at 10 mg/kg and 50 mg/kg (4 × doses, 4 h apart) showed no adverse clinical effects and no observable histological effects in any of the organs examined. In a bioluminescent S. aureus sepsis challenge model, mice that received four oral doses of NCL179 at 50 mg/kg at 4 h intervals exhibited significantly reduced bacterial loads, longer survival times and higher overall survival rates than the vehicle-only treated mice. These results support NCL179 as a valid candidate for further development to treat MDR bacterial infections as a stand-alone antibiotic or in combination with existing antibiotic classes.

Author(s):  
Mariana Ferreira ◽  
Lucinda J. Bessa ◽  
Carla F. Sousa ◽  
Peter Eaton ◽  
Dafne Bongiorno ◽  
...  

Fluoroquinolones (FQs) are antibiotics commonly used in clinical practice, although nowadays they are becoming ineffective due to the emergence of several mechanisms of resistance in most bacteria. The complexation of FQs with divalent metal ions and phenanthroline (phen) is a possible approach to circumvent antimicrobial resistance, since it forms very stable complexes known as metalloantibiotics. This work is aimed at determining the antimicrobial activity of metalloantibiotics of Cu(II)FQphen against a panel of multidrug-resistant (MDR) clinical isolates and to clarify their mechanism of action. Minimum inhibitory concentrations (MICs) were determined against MDR isolates of Escherichia coli, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). Metalloantibiotics showed improved antimicrobial activity against several clinical isolates, especially MRSA. Synergistic activity was evaluated in combination with ciprofloxacin and ampicillin by the disk diffusion and checkerboard methods. Synergistic and additive effects were shown against MRSA isolates. The mechanism of action was studied though enzymatic assays and atomic force microscopy (AFM) experiments. The results indicate a similar mechanism of action for FQs and metalloantibiotics. In summary, metalloantibiotics seem to be an effective alternative to pure FQs against MRSA. The results obtained in this work open the way to the screening of metalloantibiotics against other Gram-positive bacteria.


Author(s):  
Logan Gildea ◽  
Joseph Ayariga ◽  
James Abugri ◽  
Robert Villafane

The emergence of multidrug-resistant bacterial strains, especially in the clinical setting, has renewed interest in alternative treatment methods. The utilization of prokaryotic viruses in phage therapy has demonstrated potential as a novel treatment method against multidrug-resistant bacterial infections. As the post-antibiotic era quickly approaches, the development and standardization of phage therapy is critically relevant to public health. This review serves to highlight the development of phage therapy against methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant bacterial strain responsible for severe clinical infections.


2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Haipeng Zhang ◽  
Jingrui Chen ◽  
Yuehua Liu ◽  
Qijun Xu ◽  
Muhammad Inam ◽  
...  

AbstractGiven a serious threat of multidrug-resistant bacterial pathogens to global healthcare, there is an urgent need to find effective antibacterial compounds to treat drug-resistant bacterial infections. In our previous studies, Bacillus velezensis CB6 with broad-spectrum antibacterial activity was obtained from the soil of Changbaishan, China. In this study, with methicillin-resistant Staphylococcus aureus as an indicator bacterium, an antibacterial protein was purified by ammonium sulfate precipitation, Sephadex G-75 column, QAE-Sephadex A 25 column and RP-HPLC, which demonstrated a molecular weight of 31.405 kDa by SDS-PAGE. LC–MS/MS analysis indicated that the compound was an antibacterial protein CB6-C, which had 88.5% identity with chitosanase (Csn) produced by Bacillus subtilis 168. An antibacterial protein CB6-C showed an effective antimicrobial activity against gram-positive bacteria (in particular, the MIC for MRSA was 16 μg/mL), low toxicity, thermostability, stability in different organic reagents and pH values, and an additive effect with conventionally used antibiotics. Mechanistic studies showed that an antibacterial protein CB6-C exerted anti-MRSA activity through destruction of lipoteichoic acid (LTA) on the cell wall. In addition, an antibacterial protein CB6-C was efficient in preventing MRSA infections in in vivo models. In conclusion, this protein CB6-C is a newly discovered antibacterial protein and has the potential to become an effective antibacterial agent due to its high therapeutic index, safety, nontoxicity and great stability.


Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 427
Author(s):  
Martyna Kasela ◽  
Agnieszka Grzegorczyk ◽  
Bożena Nowakowicz-Dębek ◽  
Anna Malm

Nursing homes (NH) contribute to the regional spread of methicillin-resistant Staphylococcus aureus (MRSA). Moreover, residents are vulnerable to the colonization and subsequent infection of MRSA etiology. We aimed at investigating the molecular and phenotypic characteristics of 21 MRSA collected from the residents and personnel in an NH (Lublin, Poland) during 2018. All MRSA were screened for 20 genes encoding virulence determinants (sea-see, eta, etb, tst, lukS-F-PV, eno, cna, ebpS, fib, bbp, fnbA, fnbB, icaADBC) and for resistance to 18 antimicrobials. To establish the relatedness and clonal complexes of MRSA in NH we applied multiple-locus variable-number tandem-repeat fingerprinting (MLVF), pulse field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. We identified four sequence types (ST) among two clonal complexes (CC): ST (CC22) known as EMRSA-15 as well as three novel STs—ST6295 (CC8), ST6293 (CC8) and ST6294. All tested MRSA were negative for sec, eta, etb, lukS-F-PV, bbp and ebpS genes. The most prevalent gene encoding toxin was sed (52.4%; n = 11/21), and adhesins were eno and fnbA (100%). Only 9.5% (n = 2/21) of MRSA were classified as multidrug-resistant. The emergence of novel MRSA with a unique virulence and the presence of epidemic clone EMRSA-15 creates challenges for controlling the spread of MRSA in NH.


2014 ◽  
Vol 33 (10) ◽  
pp. e252-e259 ◽  
Author(s):  
Cilmara P. Garcia ◽  
Juliana F. Rosa ◽  
Maria A. Cursino ◽  
Renata D. Lobo ◽  
Carla H. Mollaco ◽  
...  

2005 ◽  
Vol 21 (3) ◽  
pp. 123-128 ◽  
Author(s):  
John G Gums ◽  
Benjamin J Epstein

Background: Staphylococcus aureus is a frequent cause of infections involving the bloodstream, skin and soft tissue, and lungs in hospitalized patients. These isolates are often multidrug resistant and represent a major therapeutic challenge. Objective: To explore the susceptibilities of S. aureus to nafcillin/oxacillin, a surrogate for methicillin resistance, and the fluoroquinolones and determine whether a relationship might exist between fluoroquinolone use and the prevalence of methicillin-resistant S. aureus (MRSA). Methods: To date, 353 institutions throughout the US and Puerto Rico have enrolled in the Antimicrobial Resistance Management (ARM) Program, and data have been submitted on nearly 5 million isolates of S. aureus. Isolates submitted from 1990 through 2002 were reviewed for sensitivity to nafcillin/oxacillin, clindamycin, erythromycin, and the fluoroquinolones ciprofloxacin and levofloxacin. Results: From 1990 through 2002 inclusive, susceptibility to nafcillin/oxacillin nationally was 64.9% (n = 360,460), ranging from 62.2% in the North Central and Northeast US to 72.8% in the Southwest. Nationally, S. aureus isolates were more resistant to levofloxacin (41.4%, n = 123,868) than ciprofloxacin (38.7%, n = 256,178). The greatest change in susceptibility of S. aureus to nafcillin/oxacillin and ciprofloxacin occurred concurrently from 1998 to 2002, which may implicate fluoroquinolone use with increasing rates of MRSA infection. Conclusions: Resistance to methicillin and the fluoroquinolones has increased in concert during the past 5 years. Collectively, data from the ARM Program, along with several other investigations, support a role of fluoroquinolone use in the emergence of MRSA. These observations, along with increasing resistance among gram-positive and gram-negative pathogens, underscore the need for judicious use of fluoroquinolones.


2021 ◽  
Vol 67 (2) ◽  
pp. 3372-3382
Author(s):  
Brigitta Horváth ◽  
Ferenc Peles ◽  
Judit Gasparikné Reichardt ◽  
Edit Pocklán ◽  
Rita Sipos ◽  
...  

The presence of methicillin-resistant Staphylococcus aureus (MRSA) strains in the food chain has been confirmed by several studies in the European Union, but there are only limited data available in Hungary. The objective of the present study was to investigate the antibiotic resistance of Staphylococcus strains isolated from foods, using classical microbiological, molecular biological methods and the MALDI-TOF-MS technique, as well as the multi-locus sequence typing (MLST) of antibiotic resistant strains. During the study, 47 coagulase-positive (CPS) and 30 coagulase-negative (CNS) Staphylococcus isolates were collected. In the course of the MALDI-TOF-MS investigations, all CPS isolates (n=47) were found to be S. aureus species, while 8 different species were identified in the case of the CNS strains. Methicillin resistance was confirmed in two S. aureus strains, one of which had a sequence type not yet known, while the other MRSA strain was type ST398, which is the most common type of MRSA strain isolated from farm animals in the EU/EEA. (The abbreviation “MRSA” is often used in common parlance, but occasionally in the literature to denote “multidrug-resistant Staphylococcus aureus”. In the authors’ manuscript - the methicillin-resistant pathogen is correctly designated as such. Ed.)


2021 ◽  
Vol 52 (6) ◽  
pp. 1356-1364
Author(s):  
A. M. Abd Zaid ◽  
N. J. Kandala

The study was aimed to evaluate the prevalence of MRSA in some Iraqi hospitals and determine the most powerful methods for identification of MRSA, in order to achieve the, 278 samples were collected from different hospitals in Iraq in various intervals, 204 out of 287 were identified as Staphylococcus aureus by conventional cultural methods and microscopic characteristics and 177 isolates are identified as MRSA by using HiCrome MeReSa Agar Base medium, but 154 of 177 (87%) isolates are methicillin resistance in sensitivity test. MRSA isolates were highly resistant to β-lactam antibiotics and considered multidrug resistant (MDR) in percent of (94.9%). Touchdown PCR used to identify the isolates, 97.05% were identified as Staphylococcus aureus, while 80.88%  as MRSA.                  


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