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 ◽  
...  

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.

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Shumyila Nasir ◽  
Muhammad Sufyan Vohra ◽  
Danish Gul ◽  
Umm E Swaiba ◽  
Maira Aleem ◽  
...  

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.


Foods ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 439 ◽  
Author(s):  
Vanessa Silva ◽  
Telma de Sousa ◽  
Paula Gómez ◽  
Carolina Sabença ◽  
Madalena Vieira-Pinto ◽  
...  

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.


Author(s):  
Dan Jiang ◽  
Bi Liu ◽  
Tao Gao

: 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.


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 ◽  
...  

2002 ◽  
Vol 46 (5) ◽  
pp. 1516-1521 ◽  
Author(s):  
Takashi Ida ◽  
Ryoichi Okamoto ◽  
Masato Nonoyama ◽  
Kazuhiko Irinoda ◽  
Mizuyo Kurazono ◽  
...  

ABSTRACT We encountered three clinical isolates of methicillin-resistant Staphylococcus aureus which were susceptible to netilmicin and arbekacin in the absence of β-lactam antibiotics but which were resistant to them in the presence of β-lactam antibiotics. One of these strains, KU5801, was used to further investigate the antagonism between aminoglycosides and β-lactam antibiotics. β-Lactam antibiotics induced bacterial synthesis of aminoglycoside-6′-N-acetyltransferase and 2"-O-phosphotransferase [AAC(6′)-APH(2")] in association with decreased antimicrobial activities of aminoglycosides. A 14.4-kb EcoRI fragment that included the genes that control for β-lactam-inducible aminoglycoside resistance was cloned from a 31-kb conjugative plasmid present in KU5801. Restriction fragment mapping and PCR analysis suggested that a Tn4001-like element containing a gene encoding AAC(6′)-APH(2") was located downstream from a truncated blaZ gene. The DNA sequence between blaR1 and a Tn4001-like element was determined. The Tn4001-IS257 hybrid structure was cointegrated into the blaZ gene, and the typical sequences for the termination of transcription were not found between these regions. We deduced that antagonism of aminoglycosides by β-lactam antibiotics in isolate KU5801 involved transcription of the aac(6′)-Ie-aph(2")-Ia gene under the influence of the system regulating penicillinase production.


2012 ◽  
Vol 45 (2) ◽  
pp. 189-193 ◽  
Author(s):  
Karinne Spirandelli Carvalho Naves ◽  
Natália Vaz da Trindade ◽  
Paulo Pinto Gontijo Filho

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is spread out in hospitals across different regions of the world and is regarded as the major agent of nosocomial infections, causing infections such as skin and soft tissue pneumonia and sepsis. The aim of this study was to identify risk factors for methicillin-resistance in Staphylococcus aureus bloodstream infection (BSI) and the predictive factors for death. METHODS: A retrospective cohort of fifty-one patients presenting bacteraemia due to S. aureus between September 2006 and September 2008 was analysed. Staphylococcu aureus samples were obtained from blood cultures performed by clinical hospital microbiology laboratory from the Uberlândia Federal University. Methicillinresistance was determined by growth on oxacillin screen agar and antimicrobial susceptibility by means of the disk diffusion method. RESULTS: We found similar numbers of MRSA (56.8%) and methicillin-susceptible Staphylococcus aureus (MSSA) (43.2%) infections, and the overall hospital mortality ratio was 47%, predominantly in MRSA group (70.8% vs. 29.2%) (p=0.05). Age (p=0.02) was significantly higher in MRSA patients as also was the use of central venous catheter (p=0.02). The use of two or more antimicrobial agents (p=0.03) and the length of hospital stay prior to bacteraemia superior to seven days (p=0.006) were associated with mortality. High odds ratio value was observed in cardiopathy as comorbidity. CONCLUSIONS: Despite several risk factors associated with MRSA and MSSA infection, the use of two or more antimicrobial agents was the unique independent variable associated with mortality.


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