In Contrast to Chlamydia trachomatis, Waddlia chondrophila Grows in Human Cells without Inhibiting Apoptosis, Fragmenting the Golgi Apparatus, or Diverting Post-Golgi Sphingomyelin Transport

Abstract

bThe Chlamydiales are an order of obligate intracellular bacteria sharing a developmental cycle inside a cytosolic vacuole, with very diverse natural hosts, from amoebae to mammals. The clinically most important species is Chlamydia trachomatis. Many uncertainties remain as to how Chlamydia organizes its intracellular development and replication. The discovery of new Chlamydiales species from other families permits the comparative analysis of cell-biological events and may indicate events that are common to all or peculiar to some species and more or less tightly linked to "chlamydial" development. We used this approach in the infection of human cells with Waddlia chondrophila, a species from the family Waddliaceae whose natural host is uncertain. Compared to C. trachomatis, W. chondrophila had slightly different growth characteristics, including faster cytotoxicity. The embedding in cytoskeletal structures was not as pronounced as for the C. trachomatis inclusion. C. trachomatis infection generates proteolytic activity by the protease Chlamydia protease-like activity factor (CPAF), which degrades host substrates upon extraction; these substrates were not cleaved in the case of W. chondrophila. Unlike Chlamydia, W. chondrophila did not protect against staurosporine-induced apoptosis. C. trachomatis infection causes Golgi apparatus fragmentation and redirects post-Golgi sphingomyelin transport to the inclusion; both were absent from W. chondrophila-infected cells. When host cells were infected with both species, growth of both species was reduced. This study highlights differences between bacterial species that both depend on obligate intracellular replication inside an inclusion. Some features seem principally dispensable for intracellular development of Chlamydiales in vitro but may be linked to host adaptation of Chlamydia and the higher virulence of C. trachomatis.

Experimental challenge of pregnant cattle with the putative abortifacient Waddlia chondrophila

“…This contrasts with C. abortus infection which results in necrotising placentitis and vasculitis present throughout the full thickness of the inter-cotyledonary areas and deep within the cotyledon tissue also. It has been suggested from the observed differences in the intracellular inclusion formation, substrate sequestration and the absence of anti-apoptotic activity of W. chondrophila compared to C. trachomatis that the organism may be perhaps more akin to a facultative rather than obligate pathogen in mammalian cells, in contrast with other classical chlamydial species15. These differences have been suggested to reflect a reduced level of pathogenicity, and explain the sporadic identification of W. chondrophila associated with clinical disease.…”

Waddlia: An emerging pathogen and a model organism to study the biology of chlamydiae

“…This mitochondrial recruitment helps Waddlia to get access to large amounts of lipids and ATP, that are the required energy sources likely needed for its extended metabolic capacities and for its fast replication in a large variety of cell lines. This fast replication likely explains that W. chondrophila exhibits a faster cytotoxicity compared to C. trachomatis in HeLa human cervical epithelial cell [37]. However, some features of C. trachomatis infection, such as the arrangement of cytoskeletal structures around the inclusions, degradation of host cell proteins by proteolytic activity, inhibition of apoptosis, fragmentation of the Golgi apparatus and sphingomyelin transport to inclusion, were not observed during W. chondrophila infection [36,37].…”

“…This fast replication likely explains that W. chondrophila exhibits a faster cytotoxicity compared to C. trachomatis in HeLa human cervical epithelial cell [37]. However, some features of C. trachomatis infection, such as the arrangement of cytoskeletal structures around the inclusions, degradation of host cell proteins by proteolytic activity, inhibition of apoptosis, fragmentation of the Golgi apparatus and sphingomyelin transport to inclusion, were not observed during W. chondrophila infection [36,37]. These differences may be associated with different tissue tropism and divergent pathogenetic mechanisms.…”

“…Moreover, W. chondrophila grows rapidly in a large variety of host cells and induce faster cytotoxicity compared to other Chlamydiales [4,31,32,37].…”

MAPK Activation Is Essential for Waddlia chondrophila Induced CXCL8 Expression in Human Epithelial Cells

“…Expression of these pro-inflammatory mediators occurs through distinct signalling pathways whose stimulation is through interactions of the host cells with specific pathogen associated molecular patterns (PAMPS) [ 7 ]. Comparative studies have demonstrated distinct differences in the membrane structure [ 8 ] and the developmental cycle [ 9 ] of W . chondrophila compared to other pathogenic chlamydial species, which have been suggested to reduce the pathogenicity of the organism.…”