Pyocyanin Inhibits Chlamydia Infection by Disabling Infectivity of the Elementary Body and Disrupting Intracellular Growth

Abstract

The obligate intracellular bacterium is a widespread human pathogen that causes serious problems, including (but not limited to) infertility and blindness. Our search for novel antichlamydial metabolites from marine-derived microorganisms led to the isolation of pyocyanin, a small compound from Pyocyanin is an effective antichlamydial for all three spp. tested. It has a 50% inhibitory concentration (IC) of 0.019 to 0.028 μM, which is comparable to the IC of tetracycline. At concentrations as low as 0.0039 μM, pyocyanin disables infectivity of the chlamydial elementary body (EB). At 0.5 μM or higher concentrations, the continuous presence of pyocyanin also inhibits chlamydial growth in the inclusion during later stages of the developmental cycle. Oxidative stress, a major known antimicrobial mechanism of pyocyanin, appears to be responsible only for the inhibition of bacterial growth and not for the disinfection of EBs. Pyocyanin is well-tolerated by probiotic vaginal spp. Our findings suggest that pyocyanin is of therapeutic value for chlamydial infections and can serve as a valuable chemical probe for studying chlamydial biology.

Inhibitory Activity of Pyrroloisoxazolidine Derivatives against Chlamydia trachomatis

“…Pyrroloisoxazolidines Inhibited C. trachomatis in a Dose-Dependent Manner. The antichlamydial activity of eighteen synthetic pyrroloisoxazolidines was screened by determining their inhibitory effect on the generation of infectious progeny EBs at concentration doubly increased from 1 to 32 μM against C. trachomatis D and L2 [22,34]. The IC 50 values were calculated from percent inhibition data and presented in Table 1.…”

“…Until now, there is no effective vaccine for human use. These facts necessitate the continuous efforts to discover and develop novel nonantibiotic antichlamydial agents [16][17][18][19][20][21][22][23][24][25]. In search for antichlamydial agents from the synthesized compounds, we firstly reported that a group of pyrroloisoxazolidines inhibited C. trachomatis propagation.…”

“…Uninfected HeLa cells were cultured with 32 μ M (the highest concentration used in antichlamydial analysis) of individual compound or 0.5% DMSO for 48 h. After 10 μ L of WST-1 reagent was added, cells were incubated for an additional 1 h, and absorbance at 450 nm was recorded. The viability of compound-treated cells was calculated by the absorbance relative to that of DMSO control setting as 100% [ 22 ].…”

“…However, no effective vaccine is available to prevent C. trachomatis infections up to date [13][14][15]. All these negative situations raise the pressing need to search for novel antichlamydial agents from natural materials or synthesized chemicals [16][17][18][19][20][21][22][23][24][25]. Isoxazolidine derivatives are a group of chemicals that possess a variety of biological and pharmaceutical activities including neuroactive, antioxidant, antibacterial, antifungal, and antiretroviral properties [26][27][28][29][30].…”

Marine Bacteria Is the Cell Factory to Produce Bioactive Pigments: A Prospective Pigment Source in the Ocean

“…Liang et al (2017) isolated six phenazines from Streptomyces sp., 182SMLY with three new phenazine compound (-)-streptophenazines M-O and three already known phenazine 1-carbomethoxyphenazine; (-)streptophenazines A; streptophenazines B where it was tested against the proliferation of glioma cell lines but didn't have any inhibitory effect on proliferating glioma cells and it was also screened against E. coli and MRSA, but only streptophenazines B was effective against MRSA compared to control norfloxacin which inhibited both E. coli and MRSA. Phenazine compound pyocyanin has been isolated from marine P. aeruginosa by Li et al (2018), and demonstrated to be acting as an antichlamydial agent with a dose of IC50 (0.02 µM) inhibiting its infectivity by directly targeting Elementary body (EB) but low doses didn't seem to increase the host ROS. The IC50 dose of pyocyanin did not show any immune suppressant activity and performed equally to the IC50 dose of Tetracycline against MRSA supporting the clinical use of pyocyanin for treatment.…”