Chlamydia pneumoniae

Throughout their known history, the phylogenetically distinct bacteria in phylum Chlamydiae have fascinated scientists due to their unique morphology and survival strategies. The main human pathogens among this group of obligate intracellular paracites are C. trachomatis, a sexually transmitted species, and C. pneumoniae, a ubiquitous pathogen primarily infecting the respiratory tract.

According to seroepidemiological data, the vast majority of Western population is infected by C. pneumoniae at some stage of their life, the clinical picture of the infection varying from asymptomatic to severe pneumonia. While the first reports on antimicrobial drug resistance among chlamydial species have emerged within recent years, the major therapeutic challenge with these infectious agents lies in their inherent propensity for persistence.  The non-replicating persistent form of the bacterium, triggered by host cell innate responses and environmental factors such as beta-lactam antibiotics may reside within the infected cells for years. Due to its ability to manipulate the local microenvironment to favour its survival, it predisposes its carriers to a long-lasting inflammatory state. Collectively, these aspects form the basis for C. pneumoniae being suggested as a risk factor for chronic inflammatory diseases.

Finding therapeutic strategies capable of eradicating the persistent forms of C. pneumoniae infections, as well as suppressing its pathological consequences, is the leading principle of the Chlamydia team. To reach this goal, the nonconventional antichlamydial agents we have identified serve as invaluable tools for probing chlamydia – host interactions.

We have identified the first-in-class C. pneumoniae chemosensitizer schisandrin, which remarkably enhances C. pneumoniae eradication by the standard of care antibiotic azithromycin. Profiling of this natural product and other compounds of interest is carried out by applying proteomics and in silico methods. Our main infection model is based on monocyte-derived macrophages, which allows following of the balance between simultaneously present persistent and productive bacterial populations. In addition, in vivo profiling of the compounds of interest are carried out using Caenorhabditis elegans.

Schisandrin effect on Chlamydia pneumoniae

Besides eradicating or sensitizing the persistent C. pneumoniae infection, we believe that the next generation antichlamydial compounds must prevent or alleviate the infection-induced inflammation. Thus, we also work actively on profiling the immunomodulatory properties of the compounds of interest. This work involves, among other things, studying the dissemination of C. pneumoniae from epithelium to monocytes and the infection-induced foam cell formation.

 

For more details on our recent findings, see:

1.       Taavitsainen, E., Kortesoja, M., Bruun, T., Johansson, N., Hanski, L. 2020. Assaying Chlamydia pneumoniae persistence in monocyte-derived macrophages identifies dibenzocyclooctadiene lignans as phenotypic switchers. Molecules 25(2), 294; doi:10.3390/molecules25020294, 2020

2.       Kortesoja, M., Trofin, R.E., Hanski, L. A platform for studying the transfer of Chlamydia pneumoniae between respiratory epithelium and phagocytes. J Microbiol Meth 2020 Jan 29:105857. doi: 10.1016/j.mimet.2020.105857.

3.       Kortesoja, M., Karhu, E., Olavsdottir, E., Freysdottir, J., Hanski, L. 2019. Impact of dibenzocyclooctadiene lignans on the redox status and activation of human innate immune system cells. Free Rad Biol Med. 131: 309-17.

4.       Hanski, L. and Vuorela, PM. Lead discovery strategies for identification of Chlamydia pneumoniae inhibitors. Microorganisms. 2016. 4: E43.