Early intracellular trafficking of Waddlia chondrophila in human macrophages

Abstract

Waddlia chondrophila is an obligate intracellular bacterium considered as a potential agent of abortion in both humans and bovines. This member of the order Chlamydiales multiplies rapidly within human macrophages and induces lysis of the infected cells. To understand how this Chlamydia-like micro-organism invades and proliferates within host cells, we investigated its trafficking within monocyte-derived human macrophages. Vacuoles containing W. chondrophila acquired the early endosomal marker EEA1 during the first 30 min following uptake. However, the live W. chondrophila-containing vacuoles never co-localized with late endosome and lysosome markers. Instead of interacting with the endosomal pathway, W. chondrophila immediately colocalized with mitochondria and, shortly after, with endoplasmic reticulum-(ER-) resident proteins such as calnexin and protein disulfide isomerase. The acquisition of mitochondria and ER markers corresponds to the beginning of bacterial replication. It is noteworthy that mitochondrion recruitment to W. chondrophila inclusions is prevented only by simultaneous treatment with the microtubule and actin cytoskeleton-disrupting agents nocodazole and cytochalasin D. In addition, brefeldin A inhibits the replication of W. chondrophila, supporting a role for COPI-dependent trafficking in the biogenesis of the bacterial replicating vacuole. W. chondrophila probably survives within human macrophages by evading the endocytic pathway and by associating with mitochondria and the ER. The intracellular trafficking of W. chondrophila in human macrophages represents a novel route that differs strongly from that used by other members of the order Chlamydiales.

Simkania negevensis, an insight into the biology and clinical importance of a novel member of the Chlamydiales order

“…In addition to the strong ER association, some association with the mitochondria was observed in mammal's cells in mammal's cells, similarly to what is observed for W. chondrophila (Croxatto & Greub, 2010) and C. psittaci (Mehlitz et al, 2014). However, the phenotype of mitochondria association to the replicative vacuole is much stronger for W. chondrophila, which recruits mitochondria as early as 3 h post-infection using a redundant mechanism based on both microtubules and actin microfilaments (Croxatto & Greub, 2010).…”

“…However, the phenotype of mitochondria association to the replicative vacuole is much stronger for W. chondrophila, which recruits mitochondria as early as 3 h post-infection using a redundant mechanism based on both microtubules and actin microfilaments (Croxatto & Greub, 2010). Mitochondria might represent an additional source of lipids, as well as ATP (Croxatto & Greub, 2010). It is still unclear whether S. negevensis has developed a specific mechanism to recruit the mitochondria, or if their association to the SCV is related to their natural association with the ER.…”

The Swiss Society of Microbiology: Small Bugs, Big Questions and Cool Answers

“…While the concept of culturing that is at the root of conventional bacteriology has not changed much since the Pasteurian times, the identification of bacteria and fungi has considerably been improved and accelerated (it requires 24 h now vs. 48 h before, i.e. through the use of MALDI-TOF [1] mass spectrometry). The automation of laboratories that is currently being implemented should bring more standardization in the diagnostic process and improve the overall quality of results.…”

Discovery of Catalases in Members of the Chlamydiales Order

“…(2), or facultative intracellular bacteria, such as Legionella pneumophila (3), Brucella abortus (4), and Mycobacterium tuberculosis (5). Among members of the Chlamydiales order, Chlamydia trachomatis (serovar K9) does not resist macrophage microbicidal effectors (6), whereas Waddlia chondrophila is able to replicate very efficiently in macrophages (7,8) and Parachlamydia acanthamoebae is able to replicate to a lower extent, rapidly inducing the apoptotic death of the macrophage (9)(10)(11).…”