Endolysin: A therapeutic alternative for antibiotic resistant pathogens causing urinary tract infections

Author(s): Abdul Basit*, Hamza Tahir

Urinary tract infections (UTIs) caused by pathogenic bacteria is the most frequent clinical condition affecting almost 150 million population each year worldwide, resulting in a huge economic losses due to clinical presentation. The UTIs treated with antibiotics show post treatment complications, which include repeated recurrence, pyelonephritis, renal damage, irreversible loss to kidney tissue during retrograde proliferation leading to severe risk of bacteremia with a major risk of antibiotic resistance due to recurring infections. Bacteriophage-encoded endolysin have been oftentimes recognized as a promising antibacterial agent to eradicate antibiotic-resistant bacteria due to their host specific nature and less chances of resistance development in bacterial pathogens. Endolysin kill bacterial pathogens by hydrolyzing peptidoglycan lyer in cell wall. Though large number of lytic enzymes has been reported against various MDR gram positive bacteria, very few reported against gram negative bacterial pathogens, due to their outer membrane, which acts as a barrier to cross by endolysin to hydrolyze peptidoglycan. Therefore, treatment of MDR gram negative pathogens through lytic enzymes is high challenging. However, engineering of endolysin by fusion of membrane rupturing protein can increase its access to the target site in cell wall. The fusion molecule will increase the host range and provide a path to treat common UTIs caused by gram negative and positive pathogens. This commentary is focusing on how, endolysin can be effectively modified to increase their efficiency against Multi drug resistant bacterial pathogens.
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