Strategy To Learn GPX5 Exactly Like A Champ

ESBL genes are consecutively expressed and can be transfer to other bacterial species by horizontal gene transfer via mobile elements such as plasmids and transposons (Bradford, 2001; Warnes et al., 2012). These mechanisms of transmission effectively accelerate the spread of MDR bacteria causing nosocomial outbreaks worldwide. Because ESBL-producing strains present often MDR phenotypes, in order to overcome their global resistance, new approaches in drug discovery and designs are needed. These challenges led to re-new interest in natural products as an untapped reservoir for drug discovery (Koehn and Carter, 2005; Molinari, 2009; Hayashi et al., 2013). Our recent research into nature of antibacterial compounds in honey led to isolation and sequence identification of glycoproteins as compounds chiefly responsible for honey antibacterial GPX5 activity (Brudzynski and Sjaarda, 2014, 2015). MALDI TOF and electrospray quadrupole time of flight mass spectrometry (ESI-Q-TOF-MS/MS) analysis of glycoproteins (glps) showed sequence identity with the Major Royal Jelly Proteins 1 precursor (MRJP1). We have documented that the full-length glps were able to (a) agglutinate bacterial cells due to a several high-mannose structures attached to protein backbone and (b) were able to induce phenotypic changes, (c) increase bacterial membranes permeability and (d) to cause cell lysis. The time-kill kinetics showed a rapid, >5-log10 reduction of viable cells after addition of glps to bacterial cultures (Brudzynski and Sjaarda, 2015). The MRJP1 has been implicated in several cellular functions in honeybee (Schmitzova et al., 1998; Albert et al., 1999; Kupke et al., 2012; Buttstedt et al., 2014) but it has never been linked before to antibacterial effects of honey. The MRJP1 glycoprotein harbors three antimicrobial peptides, Jelleins (Fontana et al., 2004). Synthetic Jelleins showed antibacterial activity in vitro against Gram-positive and Gram-negative bacteria (Fontana et al., 2004). The glps effects on cell morphology, growth rate and bactericidal activity resembled the action of ��-lactam antibiotics on cell envelope (Brudzynski and Sjaarda, 2014, 2015). The full length glps and the ��-lactams (penicillins, cephalosporins, carbapenems), polymyxins and glycopeptides (vancomycin and teicoplanin) share the ability to cause perturbation of the bacterial cell wall and the membrane integrity. The above classes of drugs structurally differ between each other and affect the membrane integrity by different mechanisms (Bush et al., 1995; Bush, 2012). The unexpected, novel function of MRJP1-containing glycoproteins, its antibacterial activity, is our very recent finding and the mode of action of glps has yet to be elucidated.