Natural Products for the Treatment of Chlamydiaceae Infections

Abstract

Due to the global prevalence of Chlamydiae, exploring studies of diverse antichlamydial compounds is important in the development of effective treatment strategies and global infectious disease management. Chlamydiaceae is the most widely known bacterial family of the Chlamydiae order. Among the species in the family Chlamydiaceae, Chlamydia trachomatis and Chlamydia pneumoniae cause common human diseases, while Chlamydia abortus, Chlamydia psittaci, and Chlamydia suis represent zoonotic threats or are endemic in human food sources. Although chlamydial infections are currently manageable in human populations, chlamydial infections in livestock are endemic and there is significant difficulty achieving effective treatment. To combat the spread of Chlamydiaceae in humans and other hosts, improved methods for treatment and prevention of infection are needed. There exist various studies exploring the potential of natural products for developing new antichlamydial treatment modalities. Polyphenolic compounds can inhibit chlamydial growth by membrane disruption, reestablishment of host cell apoptosis, or improving host immune system detection. Fatty acids, monoglycerides, and lipids can disrupt the cell membranes of infective chlamydial elementary bodies (EBs). Peptides can disrupt the cell membranes of chlamydial EBs, and transferrins can inhibit chlamydial EBs from attachment to and permeation through the membranes of host cells. Cellular metabolites and probiotic bacteria can inhibit chlamydial infection by modulating host immune responses and directly inhibiting chlamydial growth. Finally, early stage clinical trials indicate that polyherbal formulations can be effective in treating chlamydial infections. Herein, we review an important body of literature in the field of antichlamydial research.

Keywords: Chlamydia; Chlamydiaceae; Chlamydiae; antibacterial; chlamydial infections; natural products.

Figure 1

Chlamydiaceae species and hosts. From Chlamydiales phylogenetic tree with contents based on near full-length 16S rRNA gene sequences obtained from Genbank, NCBI. Adapted with permission from [1]. Copyright 2015 Oxford University Press.

Figure 2

The life cycle of Chlamydia trachomatis. The elementary body (EB) binds to the host cell. Compounds are injected into the host cell to initiate internalization and establish an antiapoptotic state. The EB is incorporated into an endosomal membrane to form an inclusion, which is freed from the cell wall and passes into the host cell cytoplasm. Through bacterial protein synthesis the EB converts to reticulate bodies (RBs), which redirect host cell nutrients and divide by binary fission. The RBs direct host cell function and continue to replicate exponentially. If the RBs are excessively stressed they enter a dormant persistent state to promote survival, and reactivate upon removal of stress. Within 30–48 h the RBs differentiate back to EBs, which then exit the host cell through lysis or extrusion. Adapted with permission from [28]. Copyright 2016 Nature Publishing Group.

Figure 3

Inhibition percentages of various natural and synthetic polyphenolic compounds against C. pneumoniae at 50 μM concentration (n = 4 or more). Activity is determined in comparison to controls: highly active (black bar) = 85%–100% inhibition; active (striped bar) = 50%–84%; moderately active (black dotted bar) = 30%–49%; inactive (white bar) = <30%. Adapted with permission from [43]. Copyright 2005 Elsevier Inc.

Figure 4

Scanning electron microscopy images of C. trachomatis with and without exposure to lipidic compounds. (A–D) Exposure of C. trachomatis EBs to monocaprin; The EBs were untreated (A) or treated with 10 mM monocaprin for 1 min (B); 5 min (C); and 10 min (D); With 10 min exposure the EBs appear deformed or disrupted (D, inset); Bars, 1 μm. (E,F) Exposure of C. trachomatis EBs to 1-O-hexyl-sn-glycerol; (E) C. trachomatis EBs exposed to sucrose-phosphate-glutamine buffer (SPG) only; (F) EBs exposed to 50 mM 1-O-hexyl-sn-glycerol for 90 min appear as hollow structures. Parts (A–D) are adapted with permission from [60]. Copyright 1998 American Society for Microbiology. Parts E and F are adapted with permission from [62]. Copyright 1998 American Society for Microbiology.

Figure 5

Scanning electron microscopy images of C. trachomatis exposed to cecropin peptide D2A21 for 90 min. (A) Organisms treated with D2A21 appear to be hollow or in the process of leaking their cytoplasmic contents (black arrow); (B) Untreated organisms incubated in SPG only. Bar = 0.5 μm. Adapted with permission from [69]. Copyright 2002 American Society for Microbiology.

Figure 6

Efficacy of polyherbal formulations CH-005, Praneem, and BASANT. (A) In vivo protection from Chlamydia trachomatis vaginal transmission by polyherbal formulations CH-005 and Praneem; (B) Inhibitory effect of BASANT on C. trachomatis from pre-infection incubation. The number of inclusion-forming units (IFUs) decreases with incubation time and BASANT concentration; (C) Inhibitory effect of BASANT on C. trachomatis serovar D from post-infection incubation. The minimum inhibitory concentration (MIC) was determined to be 8 μg/mL BASANT; (D) in vitro MICs of BASANT for clinical isolates of C. trachomatis from post-incubation incubation. Standard deviations from triplicate tests are indicated by error bars. Part A is adapted with permission from [91]. Copyright 2000 American Journal of Reproductive Immunology. Parts (B–D) are adapted with permission from [93]. Copyright 2008 International Society of Chemotherapy.