Poster Presentation BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

Inefficient signal peptide cleavage of the NDM-1 beta-lactamase results in lower growth rate and reduced biofilm formation (#219)

Yaramah Zalucki 1
  1. Griffith University, Southport, QLD, Australia

The New Delhi metallo beta-lactamase, (NDM-1), is a leading cause of carbapenemase resistance. Since its characterization in 2008, it has spread throughout the world and to many different bacterial species, leading to a public health crises in dealing with carbapenemase resistant bacteria. Analysis of the annotated signal peptide revealed it contained a net-negative charge at the N-terminus, due to a glutamic acid at the second position. Expression of the NDM-1 allele in Escherichia coli on an IPTG inducible plasmid resulted in high levels of unprocessed precursor when analysed by Western blot. Similarly, growth of the NDM-1 producing strains was lower and resulted in altered colony morphology compared to non-induced cells. Using a static biofilm to measure bacterial growth, we showed that induction of NDM-1 results in 2-3 fold less biofilm formation. To see if the lower biofilm formation was due to inefficient signal peptide cleavage, we replaced the second amino acid, glutamic acid, with lysine, a positively charged basic amino acid. Expression of the net-positively charged NDM-1 signal peptide resulted in efficient signal peptide cleavage and equivalent growth and colony morphology compared to non-induced cells. Similarly, there was no deficiency in biofilm formation with this construct, as opposed to the lower biofilm formation observed from expression of the wild-type NDM-1 allele.  Hence, inefficient signal peptide cleavage due to a net-negative charge at the N-terminus of the signal peptide can result in lower biofilm formation. Future clinical isolates could have an amino acid change at the second position from glutamic acid to lysine, to allow for more efficient NDM-1 expression.