Phage Lysins for Fighting Bacterial Respiratory Infections: A New Generation of Antimicrobials

Abstract

Lower respiratory tract infections and tuberculosis are responsible for the death of about 4.5 million people each year and are the main causes of mortality in children under 5 years of age. Streptococcus pneumoniae is the most common bacterial pathogen associated with severe pneumonia, although other Gram-positive and Gram-negative bacteria are involved in respiratory infections as well. The ability of these pathogens to persist and produce infection under the appropriate conditions is also associated with their capacity to form biofilms in the respiratory mucous membranes. Adding to the difficulty of treating biofilm-forming bacteria with antibiotics, many of these strains are becoming multidrug resistant, and thus the alternative therapeutics available for combating this kind of infections are rapidly depleting. Given these concerns, it is urgent to consider other unconventional strategies and, in this regard, phage lysins represent an attractive resource to circumvent some of the current issues in infection treatment. When added exogenously, lysins break specific bonds of the peptidoglycan and have potent bactericidal effects against susceptible bacteria. These enzymes possess interesting features, including that they do not trigger an adverse immune response and raise of resistance is very unlikely. Although Gram-negative bacteria had been considered refractory to these compounds, strategies to overcome this drawback have been developed recently. In this review we describe the most relevant in vitro and in vivo results obtained to date with lysins against bacterial respiratory pathogens.

Modulation of Endolysin LysECD7 Bactericidal Activity by Different Peptide Tag Fusion

“…This family of enzymes is widespread among viruses and can be found both in Gram-positive as well as in Gram-negative bacteria infecting phages. However, there are structural and functional differences between endolysins targeting Gram-positive and Gram-negative hosts [3,4]. Several "modes" of action are characteristic for endolysins, including the ability to hydrolyze either or both glycosidic and amide (including peptide) bonds [3,5].…”

“…Among the most significant advantages of using endolysins as antimicrobials is their ability to quickly and effectively lyse bacteria (even antibiotic-resistant strains and bacterial biofilms) without the development of resistance [3,6]. Thus, several endolysin molecules are currently under development [4], suggesting promising results for clinical applications.…”

Antibiotic susceptibility Patterns against Upper Respiratory Tract Pathogens in Tertiary Care Hospitals of Lahore, Pakistan

“…Several lines of literature evidences suggested that the most prevalent pathogens of URTIs include S. pneumonia, S. aureus, P. aeruginosa, E.coli, K. pneumonia and H. influenza [31], [32]. Similar bacterial pathogens have been implicated in URTIs by studies from Pakistan with minor variations in frequency distribution of bacterial pathogens [33], [34].…”

Phages for Biofilm Removal

“…Lysins are peptidoglycan hydrolases that have a bactericidal effect on susceptible bacteria. They break peptidoglycan bonds, degrading the bacterial cell wall and biofilm structure [70][71][72]. This makes lysins useful for Gram-positive bacteria [73].…”