Antibacterial Activity of Extracellular Compounds Produced by a Pseudomonas Strain Against Methicillin-Resistant Staphylococcus aureus (MRSA) Strains

Viviane F Cardozo; Admilton G Oliveira; Erick K Nishio; Marcia RE Perugini; Célia GTJ Andrade; Wanderley D Silveira; Nelson Durán; Galdino Andrade; Renata KT Kobayashi; Gerson Nakazato

Disclosures

Ann Clin Microbiol Antimicrob. 2013;12(12) 

In This Article

Abstract and Introduction

Abstract

Background: The emergence of multidrug-resistant bacteria is a world health problem. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) strains, is one of the most important human pathogens associated with hospital and community-acquired infections. The aim of this work was to evaluate the antibacterial activity of a Pseudomonas aeruginosa-derived compound against MRSA strains.

Methods: Thirty clinical MRSA strains were isolated, and three standard MRSA strains were evaluated. The extracellular compounds were purified by vacuum liquid chromatography. Evaluation of antibacterial activity was performed by agar diffusion technique, determination of the minimal inhibitory concentration, curve of growth and viability and scanning electron microscopy. Interaction of an extracellular compound with silver nanoparticle was studied to evaluate antibacterial effect.

Results: The F3 (ethyl acetate) and F3d (dichloromethane- ethyl acetate) fractions demonstrated antibacterial activity against the MRSA strains. Phenazine-1-carboxamide was identified and purified from the F3d fraction and demonstrated slight antibacterial activity against MRSA, and synergic effect when combined with silver nanoparticles produced by Fusarium oxysporum. Organohalogen compound was purified from this fraction showing high antibacterial effect. Using scanning electron microscopy, we show that the F3d fraction caused morphological changes to the cell wall of the MRSA strains.

Conclusions: These results suggest that P. aeruginosa-produced compounds such as phenazines have inhibitory effects against MRSA and may be a good alternative treatment to control infections caused by MRSA.

Introduction

The emergence of multidrug-resistant bacteria is a world health problem.[1,2] Staphylococcus aureus is one of the most important human pathogens associated with hospital and community-acquired infections. Over the last few decades, the number and proportion of methicillin-resistant S. aureus (MRSA) infections in different countries has increased due to the rise of epidemics in humans[3–5] and other animals, such as dogs, cats, cattle, pigs and exotic species.[6,7] In Brazil, according to data obtained from the first five years of the SENTRY Antimicrobial Surveillance Program, MRSA strains were among the most prevalent pathogens and contributed to 56% of the nosocomial and community infections.[8] One of the major global clones is the MRSA Brazilian epidemic clone (BEC), a hospital-acquired MRSA strain. Isolates of this strain are typically resistant to multiple antimicrobials.[9]

The expense incurred to control MRSA may be considerable; however, several economic evaluations have indicated that MRSA control programs are cost-effective in terms of reducing the costs of MRSA infections. In a study comparing two neonatal ICUs, the cost of instituting control measures in a stepwise, delayed approach was US$ 49–69 million (€ 38–52 million), while the cost of introducing effective and immediate measures was US$ 1.3 million (€ 1 million).[10] Another study calculated that the total cost per case of bacteremia that was caused by an antibiotic-resistant strain, including MRSA (50% of the cases), was US$ 88,445.[11]

The health risks associated with MRSA infections, including its potential to produce invasive infections, particularly in vulnerable patients, and its resistance to multiple antibiotics, warrant the implementation of monitoring programs to control its dissemination. There is a considerable epidemiological interest in tracking strains to gain a more complete picture of the distribution of strains in the population and the dynamics of clonal spread.[12] For years, vancomycin has been used as the drug of choice to treat MRSA infections and was recommended by clinical guidelines; however, the emergence of the vancomycin-resistant S. aureus (VRSA) and vancomycin-intermediate S. aureus (VISA) has made antibacterial therapy difficult. Therefore, new chemotherapeutic compounds to treat and control infections by these microorganisms have been broadly studied and developed.[13]

Recently, some natural antibacterial agents, such Quercus dilatata, Hylomecon hylomeconoides, Eleutherine Americana, Chelidonium majus Linn. (Papaveraceae) and Tabebuia avellanedae compounds, have been tested against MRSA.[14–18]

The ability of antibacterial compounds obtained from other bacteria to inhibit methicillin-sensitive S. aureus (MSSA) and MRSA has also been tested.[19–21] Other bacterial compounds known to have antibacterial activity have not been tested against MRSA. We have tested an extracellular compound derived from Pseudomonas aeruginosa that has previously been shown to have antibacterial effects against Xanthomonas citri pv. Citri, which causes citrus cancer lesions.[22]

The aim of this work was to evaluate the antibacterial activity of a compound from P. aeruginosa against MRSA strains.

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