Is lipopolysaccharide a factor in infectivity of Chlamydia trachomatis?

Abstract

Lipopolysaccharide (LPS) is a major surface component of Chlamydia trachomatis, as with all Gram-negative bacteria. The effect of C. trachomatis LPS on C. trachomatis infectivity of human epithelial cells was investigated. C. trachomatis LPS and C. trachomatis LPS antibody significantly reduced infectivity, mostly in a dose-dependent manner. As the structure of LPS in C. trachomatis is simple and consists only of lipid A and 3-deoxy-D-manno-octulosonic acid (Kdo), we investigated whether lipid A or Kdo was inhibitory to chlamydial infectivity. Polymyxin B, as a lipid A inhibitor, and Kdo considerably reduced C. trachomatis infectivity. With all the LPS inhibitors used, there was greater inhibition against serovar E than serovar LGV. These results suggest a role for LPS in chlamydial infectivity. Elucidation of how LPS acts in infectivity and identification of host-cell receptors would help in understanding pathogenicity.

Lipopolysaccharide-Binding Alkylpolyamine DS-96 Inhibits Chlamydia trachomatis Infection by Blocking Attachment and Entry

“…The idea of differential requirements for infectivity between serovars and various species of Chlamydia is well accepted, especially for the specific ligand-receptor interactions during bacterial attachment and entry (27). In support of our findings, it has been reported that C. trachomatis serovar E was more susceptible to various LOS inhibitors than serovar LGV in vitro (19). Clearly, it will be critical to evaluate the efficacy of DS-96, and further developed chemical analogs, using clinically relevant serovars of Chlamydia in animal challenge studies.…”

“…Fadel and Eley postulated a general role of LOS in Chlamydia infectivity (19). They demonstrated that infection of human epithelial cells by C. trachomatis serovar LGV and serovar E was inhibited in the presence of purified LOS, PMB, antibody against C. trachomatis LOS, and synthetic Kdo (19).…”

“…They demonstrated that infection of human epithelial cells by C. trachomatis serovar LGV and serovar E was inhibited in the presence of purified LOS, PMB, antibody against C. trachomatis LOS, and synthetic Kdo (19). Similar to our study, a role of Chlamydia LOS in adherence was also suggested (19). More recently, Nguyen et al examined the biological significance of Chlamydia LOS using LOS biosynthesis inhibitors (LpxC inhibitors) and proposed a crucial role of LOS in proper morphological transition of RBs to EBs (30).…”

“…Other studies have used Chlamydia LOS as a target for disruption of the developmental cycle, and various functions have been proposed (19,30). Fadel and Eley postulated a general role of LOS in Chlamydia infectivity (19).…”

“…Importantly, daily administration of DS-96 at concentrations 10-fold higher than the fully protective dose resulted in no detectable toxicity in a mouse study (12). In Chlamydia, PMB treatment of the organism has been demonstrated to significantly decrease infectivity in cell culture infection (17)(18)(19) and also to impair the bacterial membrane integrity (20). Despite its effectiveness, clinical use of unmodified PMB is limited due to the associated side effects on the eukaryotic hosts (21).…”