title: Pseudomonas Aeruginosa Lectins As Targets for Novel Antibacterials.
abstract: Pseudomonas aeruginosa is one of the most widespread and troublesome opportunistic pathogens that is capable of colonizing various human tissues and organs and is often resistant to many currently used antibiotics. This resistance is caused by different factors, including the acquisition of specific resistance genes, intrinsic capability to diminish antibiotic penetration into the bacterial cell, and the ability to form biofilms. This situation has prompted the development of novel compounds differing in their mechanism of action from traditional antibiotics that suppress the growth of microorganisms or directly kill bacteria. Instead, these new compounds should decrease the pathogens' ability to colonize and damage human tissues by inhibiting the virulence factors and biofilm formation. The lectins LecA and LecB that bind galactose and fucose, as well as oligo- and polysaccharides containing these sugars, are among the most thoroughly-studied targets for such novel antibacterials. In this review, we summarize the results of experiments highlighting the importance of these proteins for P. aeruginosa pathogenicity and provide information on existing lectins inhibitors and their effectiveness in various experimental models. Particular attention is paid to the effects of lectins inhibition in animal models of infection and in clinical practice. We argue that lectins inhibition is a perspective approach to combating P. aeruginosa. However, despite the existence of highly effective in vitro inhibitors, further experiments are required in order to advance these inhibitors into pre-clinical studies.
authors.affiliation: Gamaleya Research Center of Epidemiology and Microbiology, Gamaleya Str., 18, Moscow, 123098, Russia ; Institute of Agricultural Biotechnology, Timiryazevskaya Str., 42, Moscow, 127550, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Grishin
authors.affiliation: Gamaleya Research Center of Epidemiology and Microbiology, Gamaleya Str., 18, Moscow, 123098, Russia.
authors.forename: M S
authors.initials: MS
authors.lastname: Krivozubov
authors.affiliation: Gamaleya Research Center of Epidemiology and Microbiology, Gamaleya Str., 18, Moscow, 123098, Russia ; Institute of Agricultural Biotechnology, Timiryazevskaya Str., 42, Moscow, 127550, Russia ; Belozersky Institute of Physical and Chemical Biology, Lomonosov Moscow State University, Leninskie Gory, 1, bld. 40, Moscow, 119991, Russia.
authors.forename: A S
authors.initials: AS
authors.lastname: Karyagina
authors.affiliation: Gamaleya Research Center of Epidemiology and Microbiology, Gamaleya Str., 18, Moscow, 123098, Russia.
authors.forename: A L
authors.initials: AL
authors.lastname: Gintsburg
keywords: LecA; LecB; Pseudomonas aeruginosa; antibiotic resistance; biofilm; inhibitor; lectin