Expression of the K54 and O4 specific antigen has opposite effects on the bactericidal activity of squalamine against an extraintestinal isolate of Escherichia coli

Abstract

Squalamine is a novel cationic steroid that possesses potent, broad spectrum, antimicrobial activity. Recent data suggests that squalamine or related compounds may be present and important in host resistance to infection in the urinary tract. Therefore, the role of the K54 capsule and the O4 specific antigen moiety of the lipopolysaccharide in protecting an extraintestinal isolate of Escherichia coli against the bactericidal activity of this novel antimicrobial compound was studied. The O4 specific antigen was important for protection against squalamine. Surprisingly, in contrast, the presence of the K54 antigen enhanced the bactericidal activity of squalamine. This is the first example, to our knowledge, in which an established virulence trait, the K54 capsule, may be detrimental to an infecting pathogen under certain circumstances. z 1998 Published by Elsevier Science B.V.

Squalamine: A Polyvalent Drug of the Future?

“…Squalamine causes the leakage of fluorescent calcium dyes from lipid vesicles as well as from either anionic or zwitterionic phospholipids. It has been demonstrated that squalamine does not act as a proton ionophore when incorporated into phospholipid large unilamelar vesicles when added externally to preformed vesicle preparation [11,19,20]. On the other hand, mechanistic studies have revealed that squalamine inhibits the sodium-hydrogen exchanger (isoform NHE 3) causing changes in intracellular pH, causing the inhibition of hydrogen ion efflux from endothelial cells with subsequent reduction in cellular proliferation [21].…”

Synthesis and Biological Activities of Naturally Functionalized Polyamines: An Overview

“…It is noteworthy that squalamine is an efficient host defense against bacteria, but some modifications can occur to protect bacteria. [97] Thus, by studying E. coli it was demonstrated that O4 specific antigen confers a protection against squalamine in vitro and potentiates urinary tract infection in a mouse model in vivo. In contrast the presence of the K54 antigen enhanced the antibacterial activity of squalamine.…”

“…In contrast the presence of the K54 antigen enhanced the antibacterial activity of squalamine. [97] It was also observed that, resistance mechanism of the bacteria becomes ineffective in presence of squalamine, because of its detergent-like mechanism of action which reduces the possibility of resistance emerging. [72,90,93] This was confirmed by attempts to isolate squalamine-resistant S. aureus strains, which failed.…”