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.

Monodisperse Sequence‐Controlled α‐l‐Fucosylated Glycooligomers and Their Multivalent Inhibitory Effects on LecB

“…It can colonize almost all kinds of tissues and organs where it forms biofilms . Biofilm‐conditioned, decreased availability of the bacteria is one of the main factors in often‐observed resistance against common antibiotics . This becomes particularly problematic in immune‐suppressed individuals, for example, suffering from AIDS, cancer, or cystic fibrosis.…”

“…This becomes particularly problematic in immune‐suppressed individuals, for example, suffering from AIDS, cancer, or cystic fibrosis. P. aeruginosa infections are symptomized by serious secondary acute and chronic pneumonia or otitis externa diffusa . Therefore it is of great importance to understand the mechanisms leading to biofilm formation and develop compounds that are able to interfere with biofilm formation while being nontoxic for the patient.…”

“…In this work we study LecB, a 11.9 kDa calcium‐dependent lectin forming homotetramers extracellularly. With four fucose binding sites at 40–50 Å distances, it is involved in the cross‐linking of P. aeruginosas ’ own extracellular glycans or host surface exposed glycolipids and glycoproteins . Due to the involvement of carbohydrate‐lectin interactions in biofilm formation, the inhibition or blocking of the lectin has been investigated in a number of studies aiming to prevent or disrupt biofilm formation .…”

“…With four fucose binding sites at 40–50 Å distances, it is involved in the cross‐linking of P. aeruginosas ’ own extracellular glycans or host surface exposed glycolipids and glycoproteins . Due to the involvement of carbohydrate‐lectin interactions in biofilm formation, the inhibition or blocking of the lectin has been investigated in a number of studies aiming to prevent or disrupt biofilm formation . Considering natural monosaccharides as ligands, LecB has the highest affinity for l ‐fucose with a K D of 2.9 µ m , while mannose and fructose are weaker binding partners .…”

“…[1] Biofilm-conditioned, decreased availability of the bacteria is one of the main factors in often-observed resistance against common antibiotics. [2] This becomes particularly problematic in immune-suppressed individuals, for example, suffering from AIDS, cancer, or cystic fibrosis. P. aeruginosa infections are symptomized by serious secondary acute and chronic pneumonia or otitis externa diffusa.…”