Host defense peptides: general overview and an update on their activity against Chlamydia spp.

Abstract

Chlamydiae are obligate intracellular bacteria that cause serious diseases in a wide range of hosts. Chlamydia trachomatis is one of the leading sexually transmitted pathogens in the world. Because vaccines are not currently available, effective drugs are essential. In both animals and humans, chlamydial infections are often treated with tetracycline or its derivatives. A stable tetracycline-resistant phenotype was described in Chlamydia suis strains from pigs in the USA and in Europe. In humans, there are reports of tetracycline treatment failure and the in vitro adaptability of C. trachomatis to evolve to antibiotic resistance has been described, suggesting the pressing need to search for alternative and effective classes of antimicrobial drugs. Host defense peptides (HDPs) are known as direct antimicrobial agents as well as innate immune modulators. Being active against multidrug-resistant bacteria, HDPs are attractive candidates as templates for new drugs. A number of studies evaluated the activity of natural and synthetic HDPs against Chlamydia spp., showing C. trachomatis to be the most sensitive among chlamydia species tested. Protegrins and α-helical peptides were the most active among the HDPs assessed.

Keywords::

• antibiotic resistance
• Chlamydia spp.
• Chlamydia trachomatis
• HDP
• host defense peptides
• therapy

Acknowledgments

We thank Prof. Massimo De Renzini and Dr. Manuela Vici from the university of Bologna for kindly providing the pictures taken with the electron microscope.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • In both animals and humans, chlamydial infections are often treated with tetracycline or its derivatives, because of their broad spectrum of activity, low toxicity, excellent tissue distribution and relatively low cost.

• • A stable resistance pattern associated with genomic tet(C) islands integrated into the chlamydial chromosome has been described in Chlamydia suis strains from pigs in USA and in Europe.

• • In humans, although there are reports of tetracycline treatment failure, a stable antibiotic resistance in isolates from chlamydial infections has not yet been substantiated.

• • The in vitro horizontal transfer of tetracycline-resistant marker from C. suis to other related chlamydiae including Chlamydia trachomatis and Chlamydia muridarum, when co-cultivated in the same cell culture environment, was described suggesting serious public health implications and the pressing need to search for alternative drugs.

• • HDPs are known as direct antimicrobial agents as well as innate immune modulators, having diverse range of targets, including Gram-positive and Gram-negative bacteria, parasites, fungi, yeast, enveloped viruses and cancer cells.

• • The antimicrobial activity of most HDPs is very rapid when compared to that of antibiotics and is expressed at concentrations very similar to antibiotic MICs. These compounds can affect some multidrug-resistant bacteria: this reason makes them interesting candidates in the development of new drugs.

• • A number of studies evaluated the activity of natural and synthetic HDPs against Chlamydia spp., showing C. trachomatis the most sensitive among chlamydia species tested. Protegrins and α-helical peptides resulted more active among the HDPs assessed.

• • To date, all the studies were performed considering the in vitro antichlamydial activity of individually tested HDPs against the most common C. trachomatis serovars. HDP combinations could be tested against all C. trachomatis urogenital serovars.