Diverse Stress-Inducing Treatments cause Distinct Aberrant Body Morphologies in the Chlamydia-Related Bacterium, Waddlia chondrophila

Abstract

Chlamydiae, such as Chlamydia trachomatis and Chlamydia pneumoniae, can cause chronic infections. It is believed that persistent forms called aberrant bodies (ABs) might be involved in this process. AB formation seems to be a common trait of all members of the Chlamydiales order and is caused by distinct stress stimuli, such as β-lactam antibiotics or nutrient starvation. While the diverse stimuli inducing ABs are well described, no comprehensive morphological characterization has been performed in Chlamydiales up to now. We thus infected mammalian cells with the Chlamydia-related bacterium Waddlia chondrophila and induced AB formation using different stimuli. Their morphology, differences in DNA content and in gene expression were assessed by immunofluorescence, quantitative PCR, and reverse transcription PCR, respectively. All stimuli induced AB formation. Interestingly, we show here for the first time that the DNA gyrase inhibitor novobiocin also caused appearance of ABs. Two distinct patterns of ABs could be defined, according to their morphology and number: (i) small and multiple ABs versus (ii) large and rare ABs. DNA replication of W. chondrophila was generally not affected by the different treatments. Finally, no correlation could be observed between specific types of ABs and expression patterns of mreB and rodZ genes.

Transcriptional Landscape of Waddlia chondrophila Aberrant Bodies Induced by Iron Starvation

“…As due to the presence of efflux pumps in amoebae the treatment with drugs often requires higher concentrations than in mammalian cells, we chose to grow W. chondrophila in human (HEp-2) cells for the RNA-seq experiment. Moreover, we had already observed that BPDL induced the formation of ABs in W. chondrophila grown in Vero cells [29].…”

Persistence in Chlamydia

“…Aberrant bodies were first described in 1993 on Chlamydia cultured on McCoy cells and incubated in Eagle's minimal essential medium lacking all 13 amino acids [27]. Chlamydia AB formation is also induced in vitro by antibiotics (beta-lactam antibiotics, fosfomycin, novobiocin, fosmidomycin, and Azithromycin) [28][29][30][31][32][33]), depletion of essential nutrients (i.e., iron, amino acids, and glucose), heat shock, coinfection with Herpes Simplex virus [27,[34][35][36][37][38][39], infection of monocytes and macrophages [40][41][42], cytokines (Interferon-gamma and IFN-γ) [43], and a number of other pressures [44,45]. AB in certain Chlamydial species is also induced by treatment with LPC-011 (LPC), a potent inhibitor of the zinc-dependent cytoplasmic deacetylase LpxC, which catalyzed the first step in the Chlamydial Persistence in Chlamydia DOI: http://dx.doi.org/10.5772/intechopen.109299 lipooligosaccharide (LOS) biosynthesis pathway [46].…”

Temperature affects the host range of Rhabdochlamydia porcellionis and the infectivity of Waddlia chondrophila and Chlamydia trachomatis elementary bodies

“…Transient exposure to 37 °C irremediably blocks the replication of R. porcellionis Members of the Chlamydiaceae are known to enter a third non-replicative stage, the aberrant body, when exposed to stresses such as antibiotic exposure (50), nutrient deprivation (51) or heat shock (52). Aberrant bodies are typically described as non-replicating enlarged cells able to resume their regular cycle once the stress disappears, although their morphology was shown to vary in function of the stresses (53,54). We thus wondered whether R. porcellionis could similarly recover and resume its growth cycle after an exposure to 37 °C.…”