Abstract
The emergence of antibiotic-resistant pathogens has caused a serious worldwide problem in infection treatment in recent years. One of the pathogens is methicillin-resistant Staphylococcus aureus (MRSA), which is a major cause of skin and soft tissue infections. Alternative strategies and novel sources of antimicrobials to solve antibiotic resistance problems are urgently needed. In this study, we explored the potential of two broad-spectrum bacteriocins, garvicin KS and micrococcin P1, in skin infection treatments. The two bacteriocins acted synergistically with each other and with penicillin G in killing MRSA in vitro The MICs of the antimicrobials in the three-component mixture were 40 ng/ml for micrococcin P1 and 2 μg/ml for garvicin KS and penicillin G, which were 62, 16, and at least 1,250 times lower than their MICs when assessed individually. To assess its therapeutic potential further, we challenged the three-component formulation in a murine skin infection model with the multidrug-resistant luciferase-tagged MRSA Xen31, a strain derived from the clinical isolate S. aureus ATCC 33591. Using the tagged-luciferase activity as a reporter for the presence of Xen31 in wounds, we demonstrated that the three-component formulation was efficient in eradicating the pathogen from treated wounds. Furthermore, compared to Fucidin cream, which is an antibiotic commonly used in skin infection treatments, our formulation was also superior in terms of preventing resistance development.
Highlights
The emergence of multidrug-resistant bacterial pathogens is currently considered a global public health problem [1, 2]
The first observation of methicillin-resistant S. aureus (MRSA) strains among clinical isolates was made as early as 1961, just 2 years after the introduction of methicillin to treat penicillin-resistant S. aureus infections; only since the 1990s have community-associated MRSA (CA-MRSA) strains spread in the general population worldwide [6]
This is true for Garvicin KS (GarKS) and micrococcin P1 (MP1), as can be seen in Fig. 1 with an MRSA strain—with long incubation, resistant colonies of MRSA appeared within the inhibition zones where single antimicrobials were applied
Summary
The emergence of multidrug-resistant bacterial pathogens is currently considered a global public health problem [1, 2]. The Centers for Disease Control and Prevention (CDC) declared that the human race is in the “postantibiotic era,” and the World Health Organization (WHO) warned that the antibiotic resistance crisis is becoming dire [3]. Staphylococcus aureus is both a frequent commensal and one of the most important pathogenic microorganisms causing hospital- and communityacquired infections [4]. The current treatment regimen for patients hospitalized with MRSA-associated SSTIs includes vancomycin, linezolid, daptomycin, or ceftaroline [11]; S. aureus clinical isolates resistant to these antibiotics have emerged within the past 20 years [12,13,14,15]. Bacteriocins represent a great source of antimicrobials that can be exploited to combat bacterial infections, especially against antibiotic-resistant pathogens
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