Abstract
The present study demonstrates the antibacterial potential of a phage endolysin against Gram-negative pathogens, particularly against multidrug resistant strains of Acinetobacter baumannii. We have cloned, heterologously expressed and characterized a novel endolysin (ABgp46) from Acinetobacter phage vb_AbaP_CEB1 and tested its antibacterial activity against several multidrug-resistant A. baumannii strains. LC-MS revealed that ABgp46 is an N-acetylmuramidase, that is also active over a broad pH range (4.0–10.0) and temperatures up to 50°C. Interestingly, ABgp46 has intrinsic and specific anti-A. baumannii activity, reducing multidrug resistant strains by up to 2 logs within 2 h. By combining ABgp46 with several organic acids that act as outer membrane permeabilizing agents, it is possible to increase and broaden antibacterial activity to include other Gram-negative bacterial pathogens. In the presence of citric and malic acid, ABgp46 reduces A. baumannii below the detection limit (>5 log) and more than 4 logs Pseudomonas aeruginosa and Salmonella typhimurium strains. Overall, this globular endolysin exhibits a broad and high activity against Gram-negative pathogens, that can be enhanced in presence of citric and malic acid, and be used in human and veterinary medicine.
Highlights
Gram-negative (G−) pathogenic bacteria remain a global human health concern as they are common causes of foodborne, environmentally acquired, and zoonotic infectious diseases (Chopra et al, 2008; Scallan et al, 2011)
GH19 represents a class of chitinases that cleaves the unbranched chains of N-acetyl glucosamine polymers, a structure uncommon in bacterial cell walls, but some enzymes that able to degrade the PG of G− bacteria have been shown (e.g., Pseudomonas phage OBP and Salmonella phage PVP-SE1 endolysins; Walmagh et al, 2012)
The same sequence has been observed in the A. baumannii phage endolysin LysAB2, which has been shown to interfere with the A. baumannii outer membrane (OM) (Lai et al, 2011)
Summary
Gram-negative (G−) pathogenic bacteria remain a global human health concern as they are common causes of foodborne, environmentally acquired, and zoonotic infectious diseases (Chopra et al, 2008; Scallan et al, 2011). Recent in silico analysis illustrated the large diversity and complexity of endolysins that can comprise up to four domains in the same coding sequence, have 24 different types of catalytic and 15 binding domains, and 89 possible architectural organizations (Oliveira et al, 2013). In view of this tremendous diversity, endolysins have received relatively little attention, especially in terms of more fundamental aspects such as their conformation analysis as well as their its anti-G− activity
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