Perspective: Water-Filtered Infrared-A-Radiation (wIRA) – novel treatment options for chlamydial infections?

Water-filtered infrared-A-radiation (wIRA) is a promising therapeutic method, which is particularly used as supportive treatment for wound closure, and wound infection treatment and prevention. High penetration properties of the heat field and beneficial effects on wound healing processes predispose wIRA irradiation to be a non-invasive treatment method for bacterial infections in superficial tissues. Since Chlamydia trachomatis still represents the leading cause of infectious blindness in third world countries (WHO http://www.who.int/topics/trachoma/en/) and wIRA displays beneficial effects on chlamydial infections in vitro without inducing cellular damage in ex vivo eye models and also shows beneficial effects on wound healing, this irradiation technique might represent a promising future treatment for trachoma patients. To this end, further studies investigating shorter irradiation times or irradiation of Chlamydia in chronic infections [the chlamydial stress response (Bavoil, 2014)] as well as safety studies in animal models should clearly be performed

Porcine Epidemic Diarrhea Virus (PEDV) Co-Infection Induced Chlamydial Persistence/Stress Does Not Require Viral Replication

Chlamydiae may exist at the site of infection in an alternative replicative form, called the aberrant body (AB). ABs are produced during a viable but non-infectious developmental state termed persistence or chlamydial stress. As persistent/stressed chlamydiae: (i) may contribute to chronic inflammation observed in diseases like trachoma; and (ii) are more resistant to current anti-chlamydial drugs of choice, it is critical to better understand this developmental stage. We previously demonstrated that porcine epidemic diarrhea virus (PEDV) co-infection induced Chlamydia pecorum persistence/stress in culture. One critical characteristic of persistence/stress is that the chlamydiae remain viable and can reenter the normal developmental cycle when the stressor is removed. Thus, we hypothesized that PEDV-induced persistence would be reversible if viral replication was inhibited. Therefore, we performed time course experiments in which Vero cells were C. pecorum/PEDV infected in the presence of cycloheximide (CHX), which inhibits viral but not chlamydial protein synthesis. CHX-exposure inhibited PEDV replication, but did not inhibit induction of C. pecorum persistence at 24 h post-PEDV infection, as indicated by AB formation and reduced production of infectious EBs. Interestingly, production of infectious EBs resumed when CHX-exposed, co-infected cells were incubated 48-72 h post-PEDV co-infection. These data demonstrate that PEDV co-infection-induced chlamydial persistence/stress is reversible and suggest that this induction (i) does not require viral replication in host cells; and (ii) does not require de novo host or viral protein synthesis. These data also suggest that viral binding and/or entry may be required for this effect. Because the PEDV host cell receptor (CD13 or aminopeptidase N) stimulates cellular signaling pathways in the absence of PEDV infection, we suspect that PEDV co-infection might alter CD13 function and induce the chlamydiae to enter the persistent state

Water-Filtered Infrared A (wIRA) Irradiation: Novel Treatment Options for Chlamydial Infections

wIRA has been shown to reduce extracellular chlamydial forms and intracellular chlamydial inclusions in different cell culture infection models, and similarly on different human or animal chlamydial species. Repeated wIRA applications increase the efficacy of treatment in vitro, and in vivo in a guinea pig ocular model of inclusion conjunctivitis. The guinea pig model reflects the human ocular disease trachoma, the most common cause of infectious blindness worldwide which is caused by ocular strains of Chlamydia trachomatis. In this model, ocular wIRA treatment reduces conjunctival chlamydial load and ocular pathology. First insights into the mechanisms of anti-chlamydial activity indicate the involvement of both thermal and non-thermal effects. Interestingly, wIRA treatment of non-infected cells renders them more resistant to subsequent chlamydial infection, suggesting cell-related mechanisms that might involve cytochrome C. Further studies envisage the refinement of wIRA treatment protocols, the enhancement of anti-chlamydial activity by adding photodynamic substances, and characterization of the mechanisms underlying the therapeutic benefit of wIRA

Damage/Danger Associated Molecular Patterns (Damps) Modulate Chlamydia Pecorum and C. Trachomatis Serovar E Inclusion Development in Vitro

Persistence, more recently termed the chlamydial stress response, is a viable but non-infectious state constituting a divergence from the characteristic chlamydial biphasic developmental cycle. Damage/danger associated molecular patterns (DAMPs) are normal intracellular components or metabolites that, when released from cells, signal cellular damage/ lysis. Purine metabolite DAMPs, including extracellular ATP and adenosine, inhibit chlamydial development in a species-specific manner. Viral co-infection has been shown to reversibly abrogate Chlamydia inclusion development, suggesting persistence/chlamydial stress. Because viral infection can cause host cell DAMP release, we hypothesized DAMPs may influence chlamydial development. Therefore, we examined the effect of extracellular ATP, adenosine, and cyclic AMP exposure, at 0 and 14 hours post infection, on C. pecorum and C. trachomatis serovar E development. In the absence of de novo host protein synthesis, exposure to DAMPs immediately post or at 14 hours post infection reduced inclusion size; however, the effect was less robust upon 14 hours post infection exposure. Additionally, upon exposure to DAMPs immediately post infection, bacteria per inclusion and subsequent infectivity were reduced in both Chlamydia species. These effects were reversible, and C. pecorum exhibited more pronounced recovery from DAMP exposure. Aberrant bodies, typical in virus-induced chlamydial persistence, were absent upon DAMP exposure. In the presence of de novo host protein synthesis, exposure to DAMPs immediately post infection reduced inclusion size, but only variably modulated chlamydial infectivity. Because chlamydial infection and other infections may increase local DAMP concentrations, DAMPs may influence Chlamydia infection in vivo, particularly in the context of poly-microbial infections. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

Prevalence of Chlamydophila psittaci in wild birds—potential risk for domestic poultry, pet birds, and public health?

To determine the prevalence of Chlamydophila psittaci in wild birds, cloacal swabs from 527 songbirds, 442 waterfowl, 84 feral pigeons, and 38 cormorants were examined by Chlamydiaceae-specific real-time polymerase chain reaction (PCR) and ArrayTube microarray assays for chlamydial species determination and genotyping of C. psittaci. Inconclusive cases were further characterized by conventional PCR methods targeting the chlamydial outer membrane protein A, 16S, 23S, and intergenic spacer genes followed by sequencing of the PCR product. Swabs of 19 water birds (tufted ducks and pochards), 12 pigeons, and one songbird were tested positive by the Chlamydiaceae-specific real-time PCR. While C. psittaci genotypes B (n = 5) and E (n = 1) were identified in feral pigeons (n = 9), the genotype could not be identified in the remaining three cases. Sequence data of Chlamydiaceae-positive cases (n = 23; 19 waterfowl, three pigeons, one songbird) indicated the presence of nonclassified chlamydial agents (n = 20) and C. psittaci (n = 3) by 16S rRNA PCR and sequencing. In conclusion, C. psittaci was not detected in waterfowl and songbirds, but C. psittaci proved prevalent in urban feral pigeons, where it poses a significant risk for human

Perspective: Water-Filtered Infrared-A-Radiation (wIRA) – Novel Treatment Options for Chlamydial Infections?

Water-filtered infrared-A-radiation (wIRA) is a promising therapeutic method, which is particularly used as supportive treatment for wound closure, and wound infection treatment and prevention. High penetration properties of the heat field and beneficial effects on wound healing processes predispose wIRA irradiation to be a non-invasive treatment method for bacterial infections in superficial tissues. Since Chlamydia trachomatis still represents the leading cause of infectious blindness in third world countries (WHO http://www.who.int/topics/trachoma/en/) and wIRA displays beneficial effects on chlamydial infections in vitro without inducing cellular damage in ex vivo eye models and also shows beneficial effects on wound healing, this irradiation technique might represent a promising future treatment for trachoma patients. To this end, further studies investigating shorter irradiation times or irradiation of Chlamydia in chronic infections [the chlamydial stress response (Bavoil, 2014)] as well as safety studies in animal models should clearly be performed

Neisseria gonorrhoeae Limits Chlamydia trachomatis Inclusion Development and Infectivity in a Novel In Vitro Co-Infection Model

Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (Ng) are the most common bacterial sexually transmitted infections (STIs) worldwide. The primary site of infection for both bacteria is the epithelium of the endocervix in women and the urethra in men; both can also infect the rectum, pharynx and conjunctiva. Ct/Ng co-infections are more common than expected by chance, suggesting Ct/Ng interactions increase susceptibility and/or transmissibility. To date, studies have largely focused on each pathogen individually and models exploring co-infection are limited. We aimed to determine if Ng co-infection influences chlamydial infection and development and we hypothesized that Ng-infected cells are more susceptible to chlamydial infection than uninfected cells. To address this hypothesis, we established an in vitro model of Ct/Ng co-infection in cultured human cervical epithelial cells. Our data show that Ng co-infection elicits an anti-chlamydial effect by reducing chlamydial infection, inclusion size, and subsequent infectivity. Notably, the anti-chlamydial effect is dependent on Ng viability but not extracellular nutrient depletion or pH modulation. Though this finding is not consistent with our hypothesis, it provides evidence that interaction of these bacteria in vitro influences chlamydial infection and development. This Ct/Ng co-infection model, established in an epithelial cell line, will facilitate further exploration into the pathogenic interplay between Ct and Ng

wIRA: hyperthermia as a treatment option for intracellular bacteria, with special focus on Chlamydiae and Mycobacteria

The emergence of antibiotic-resistant bacteria in the last century is alarming and calls for alternative, nonchemical treatment strategies. Thermal medicine uses heat for the treatment of infectious diseases but its use in facultative and obligate intracellular bacteria remains poorly studied. In this review, we summarize previous research on reducing the infectious burden of; Mycobacterium ulcerans; and; Chlamydia trachomatis; by using water-filtered infrared A-radiation (wIRA), a special form of heat radiation with high tissue penetration and low thermal load on the skin surface.; Mycobacterium ulcerans; is a thermosensitive bacterium causing chronic necrotizing skin disease. Therefore, previous data on wIRA-induced improvement of wound healing and reduction of wound infections is summarized first. Then, pathogenesis and treatment of infections with; M. ulcerans; causing Buruli ulcer and of those with; C. trachomatis; infecting the ocular conjunctiva and resulting in blinding trachoma are discussed. Both bacteria cause neglected tropical diseases and have similar geographical distributions. Results of previous; in vitro; and; in vivo; studies using wIRA on; M. ulcerans; and; C. trachomatis; infections are presented. Finally, technical aspects of using wIRA in patients are critically reviewed and open questions driving future research are highlighted. In conclusion, wIRA is a promising tool for reducing infectious burden due to intracellular bacteria such as; M. ulcerans; and; C. trachomatis;