# Parachlamydia acanthamoebae: disease-causing pathogen or opportunistic bystander?

## TL;DR

This paper explores whether Parachlamydia acanthamoebae is a harmful pathogen or a harmless bystander in human respiratory infections.

## Contribution

It reviews current knowledge on the bacterium's pathogenic potential and highlights gaps in understanding and diagnosis.

## Key findings

- Parachlamydia acanthamoebae is found in amoebae and may infect human respiratory cells.
- The bacterium has been linked to pneumonia and bronchitis, but transmission routes remain unclear.
- Diagnostic methods include co-culture with amoebae and PCR, but testing is not routine.

## Abstract

Parachlamydia acanthamoebae is an obligate intracellular bacterium found in free-living Acanthamoeba amoebae. As with other Chlamydiales, P. acanthamoebae has a biphasic lifecycle with an infectious elementary body and a replicative reticulate body. Once inside a host, the elementary body differentiates to the reticulate body to undergo replication within the membrane-bound compartment called the inclusion. These infected amoebae can be found in many environments such as in hospitals, household water sources, lakes and farm animals. Although the exact route of transmission from amoebae to humans is unknown, it is believed that humans may breathe in the Parachlamydia-infected amoebae. The amoebae can then reside on the respiratory epithelium within the new human host. It is possible that newly released P. acanthamoebae can then directly infect human host cells, such as macrophages, pneumocytes or lung fibroblasts, or propagate within infected amoebae. P. acanthamoebae has been found in humans with multiple respiratory infections such as pneumonia and bronchitis, indicating an association of the presence of this bacterium with severe disease. Transmission may also occur zoonotically through contact with contaminated animals. The understanding of potential complications of pregnancy associated with P. acanthamoebae infection is not understood, but there may be an association with infertility or recurrent miscarriage. Identification and diagnosis can be performed by co-culture of respiratory samples with amoebae or by quantitative PCR using primers specific to P. acanthamoebae. This bacterium is found around the world, but due to the lack of testing in patients, the incidence of infection is largely unknown.

Introduction.
Parachlamydia acanthamoebae is an obligate intracellular bacterium related to disease-causing bacteria like Chlamydia trachomatis and Chlamydia pneumoniae and is thus classified within the Chlamydiales order. Parachlamydia was initially discovered within an Acanthamoeba strain isolated from water in a humidifier during an investigation of an outbreak of respiratory infections in humans.

Gap Statement. The disease-causing potential of this bacterium is not fully understood, but Parachlamydia has been associated with bronchiolitis, bronchitis, aspiration pneumonia and community-acquired pneumonia in humans. Additionally, diagnostic testing for Parachlamydia infection is not routinely performed, indicating that prevalence is underreported.

Aim. This JMM profile aims to gauge what is currently known about the pathogenic potential of P. acanthamoebae and bring awareness to gaps in knowledge.

Results. Amoebae appear to be the main reservoir of P. acanthamoebae and likely enter the nasal passages through contaminated water sources or contact with contaminated animals. The infected amoebae may then descend to the lower respiratory tract where the lytic cycle is triggered, causing human infection.

Conclusion. By implementing serology and molecular testing, as well as conducting additional epidemiological studies, a better understanding of the association of human colonization with disease outcomes can be achieved.