Abstract
Due to the emergence of multidrug-resistant bacteria, treatment options for infectious diseases are decreasing. Bacteriocins are small antimicrobial peptides produced by numerous bacteria that offer alternative therapeutic strategies to combat multidrug-resistant bacterial infections. We evaluated the cloning, functional expression, and antimicrobial activities of enterocin P (EntP), a class II bacteriocin member, in Chinese hamster ovary (CHO) cells. A synthetic gene matching CHO cell codon usage was designed from the known mature amino acid sequence of EntP and cloned into the protein expression vector pcDNA™3.1(+). CHO cells were transformed with the recombinant plasmid and cultured, and the recombinant protein was purified by affinity chromatography. Antimicrobial activities of the recombinant EntP were evaluated on Gram-positive, Gram-negative, and multidrug-resistant pathogens. Recombinant EntP inhibited growth of a variety of bacteria, including pathogenic species known to cause nosocomial infections, often with multidrug-resistant strains. In addition, recombinant EntP demonstrated broad antimicrobial activities in both high salt medium and human plasma and was stable at high temperatures. The broad antimicrobial activity and stability of EntP make it an attractive therapeutic candidate, particularly for treatment of multidrug-resistant bacterial infections.
Highlights
Multidrug-resistant pathogenic bacteria are a major threat to global health and are rising to dangerously high levels worldwide (Jasovsky et al 2016)
Bacteriocins are a heterogeneous group of ribosomallysynthesized antimicrobial peptides (AMPs) or complex proteins secreted by Tanhaeian et al AMB Expr (2019) 9:6 bacteria that exhibit antimicrobial activity against similar or closely-related species through numerous mechanisms (Micenkova et al 2014; Shabir et al 2018)
The enterocin P (EntP) peptide C-score in (Jack et al 1996) and C-score > − 1.5 indicates a model of correct global topology
Summary
Multidrug-resistant pathogenic bacteria are a major threat to global health and are rising to dangerously high levels worldwide (Jasovsky et al 2016). The World Health Organization 2017 fact sheet warns that new antimicrobial resistance mechanisms are emerging and spreading globally, threatening our ability to treat common infectious diseases. A Bacteriocins are a heterogeneous group of ribosomallysynthesized AMPs or complex proteins secreted by Tanhaeian et al AMB Expr (2019) 9:6 bacteria that exhibit antimicrobial activity against similar or closely-related species through numerous mechanisms (Micenkova et al 2014; Shabir et al 2018). Bacteriocins are highly selective, are effective against multidrugresistant pathogens, and are non-toxic, which makes them important lead compounds for drug development (Bowdish et al 2005; Mathur et al 2018)
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