Abstract
Development of multidrug antibiotic resistance in bacteria is a predicament encountered worldwide. Researchers are in a constant hunt to develop effective antimicrobial agents to counter these dreadful pathogenic bacteria. Here we describe a chimerically engineered multimodular enzybiotic to treat a clinical isolate of methicillin-resistant Staphylococcus aureus (S. aureus). The cell wall binding domain of phage ϕ11 endolysin was replaced with a truncated and more potent cell wall binding domain from a completely unrelated protein from a different phage. The engineered enzybiotic showed strong activity against clinically relevant methicillin-resistant Staphylococcus aureus. In spite of a multimodular peptidoglycan cleaving catalytic domain, the engineered enzybiotic could not exhibit its activity against a veterinary isolate of S. aureus. Our studies point out that novel antimicrobial proteins can be genetically engineered. Moreover, the cell wall binding domain of the engineered protein is indispensable for a strong binding and stability of the proteins.
Highlights
Multidrug-resistant pathogens cause a serious threat to the health of both humans and animals
Enzybiotics are generally derived from bacteriophage endolysins, which lyse the bacterial cells at the end of the lytic replicative cycle, facilitating the release of phage progenies
In this study we investigated the antimicrobial potential of a chimeric enzybiotic against S. aureus including the clinical MRSA strain
Summary
Multidrug-resistant pathogens cause a serious threat to the health of both humans and animals. There is a low probability of the development of bacterial resistance to enzybiotics. It has been shown that enzybiotics can be used alone or in combination with traditional antibiotics, generally reducing the effective concentration of the antibiotics [1,6]. Enzybiotics are generally derived from bacteriophage endolysins, which lyse the bacterial cells at the end of the lytic replicative cycle, facilitating the release of phage progenies. This feature of the endolysin has been exploited to kill Gram-positive pathogens, when added exogenously [7]. In addition to wound infections, enzybiotics have been shown to penetrate cells and eradicate intracellular antibiotic-resistant S. aureus pathogens [12]
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