Impact of Active Metabolism on Chlamydia trachomatis Elementary Body Transcript Profile and Infectivity.
Journal of Bacteriology, 2018.
Abstract- “Bacteria of the genus Chlamydia include the significant human pathogens Chlamydia trachomatis and C. pneumoniae. All chlamydiae are obligate intracellular parasites that depend on infection of a host cell and transition through a biphasic developmental cycle. Following host cell invasion by the infectious elementary body (EB), the pathogen transitions to the replicative but noninfectious reticulate body (RB). Differentiation of the RB back to the EB is essential to generate infectious progeny. While the EB form has historically been regarded as metabolically inert, maintenance of infectivity during incubation with specific nutrients has revealed active maintenance of the infectious phenotype. Using transcriptome sequencing, we show that the transcriptome of extracellular EBs incubated under metabolically stimulating conditions does not cluster with germinating EBs but rather with the transcriptome of EBs isolated directly from infected cells. In addition, the transcriptional profile of the extracellular metabolizing EBs more closely resembled that of EB production than germination. Maintenance of infectivity of extracellular EBs was achieved by metabolizing chemically diverse compounds, including glucose 6-phosphate, ATP, and amino acids, all of which can be found in extracellular environments, including mucosal secretions. We further show that the EB cell type actively maintains infectivity in the inclusion after terminal differentiation. Overall, these findings contribute to the emerging understanding that the EB cell form is actively maintained through metabolic processes after terminal differentiation to facilitate prolonged infectivity within the inclusion and under host cell free conditions, for example, following deposition at mucosal surfaces.”
Simkania negevensis may produce long-lasting infections in human pneumocytes and endometrial cells
FEMS Pathogens and Disease, 2017.
Abstract- “Simkania negevensis is a novel Chlamydia-related bacterium and the founding member of the Simkaniaceae family within the Chlamydiales order. Little is known about the biology and pathogenesis of this bacterium. So far, S. negevensis has been considered as an amoebal symbiont, but its natural host remains unknown. Moreover, evidence of human exposition has been reported worldwide and an association with pneumonia and bronchiolitis is suspected. Here, we evaluated the ability of S. negevensis to replicate in potential environmental reservoirs, namely amoebae and arthropods, as well as in mammalian cells (Vero cells, pneumocytes and endometrial cells) and further evaluated the characteristics of its replicative vacuole. We demonstrated that S. negevensisefficiently replicates in all cell lines tested, with the shortest doubling time and an increased adhesion observed in pneumocytes. Our work highlights the specificities of the Simkania-containing vacuole compared to other Chlamydiales; contrarily to Chlamydia trachomatis, S. negevensis does not disrupt the Golgi apparatus. Importantly, our work suggests that S. negevensisinfection is associated with few cytopathic effects and might persist for a prolonged time in infected cells. Further evaluation of its implication in human diseases is required; an implication in chronic or subacute respiratory infections might be suspected.”
What is the true clinical relevance of Simkania negevensis and other emerging Chlamydiales members?
Elsevier New Microbes and New Infections, 2018.
Abstract- “Waddlia chondrophila and Simkania negevensis are emerging Chlamydia-related bacteria. Similar to the pathogenic organisms Chlamydia pneumoniae and Chlamydia trachomatis, these emerging bacteria are implicated in human genital infections and respiratory diseases. We used a screening strategy based on a newly developed S. negevensis–specific quantitative real-time PCR(qPCR) and a pan-Chlamydiales qPCR. We could not detect S. negevensis in 458 respiratory, genitourinary, cardiac and hepatic samples tested. One urethral swab was positive for W. chondrophila.We observed a low prevalence of Chlamydiales in respiratory samples (1/200, 0.5%), which suggests that C. pneumoniae is an uncommon respiratory pathogen. Furthermore, we screened 414 human serum samples from Switzerland, England and Israel and observed a low prevalence (<1%) of exposure to S. negevensis.Conversely, humans were commonly exposed to W. chondrophila,with seroprevalences ranging from 8.6% to 32.5%. S. negevensis is not a clinically relevant pathogen, but further research investigating the role of W. chondrophila is needed.”
Simkania negevensis, an insight into the biology and clinical importance of a novel member of the Chlamydiales order
Critical Reviews in Microbiology, 2017.
Abstract- “Simkania negevensis is a Chlamydia-related bacterium discovered in 1993 and represents the founding member of the Simkaniaceae family within the Chlamydiales order. As other Chlamydiales, it is an obligate intracellular bacterium characterized by a biphasic developmental cycle. Its similarities with the pathogenic Chlamydia trachomatis and Chlamydia pneumoniae make it an interesting bacterium. So far, little is known about its biology, but S. negevensis harbors various microbiological characteristics of interest, including a strong association of the Simkania-containing vacuole with the ER and the presence of an intron in the 23S rRNA encoding gene. Evidence of human exposition has been reported worldwide. However, there is a lack of robust clinical studies evaluating its implication in human diseases; current data suggest an association with pneumonia and bronchiolitis making S. negevensis a potential emerging pathogen. Owing to its fastidious growth requirements, the clinical relevance of S. negevensis is probably underestimated. In this review, we summarize the current knowledge on S. negevensis and explore future research challenges.”
Waddlia chondrophila: from biology to pathogenicity
Elsevier Microbes and Infection, 2013.
Abstract- “Waddlia chondrophila is an emerging pathogen causing miscarriages in humans and abortions in ruminants. The full genome of this Chlamydia-related bacterium has been recently completed, providing new insights into its biology and evolution. Moreover, new cell biology approaches and the use of novel inhibitors have allowed detailed investigations of its interaction with host cells.”
Pathogenic Potential of Novel Chlamydiae and Diagnostic Approaches to Infections Due to These Obligate Intracellular Bacteria
Clinical Microbiology Reviews, 2006.
Summary- “Novel chlamydiae are newly recognized members of the phylum Chlamydiales that are only distantly related to the classic Chlamydiaceae, i.e., Chlamydia and Chlamydophila species. They also exibit an obligate biphasic intracellular life cycle within eukaryote host cells. Some of these new chlamydiae are currently considered potential emerging human and/or animal pathogens. Parachlamydia acanthamoebae and Simkania negevensis are both emerging respiratory human pathogens, Waddlia chondrophila could be a novel abortigenic bovine agent, and Piscichlamydia salmonis has recently been identified as an agent of the gill epitheliocystis in the Atlantic salmon. Fritschea spp. and Rhabdochlamydia spp. seem to be confined to arthropods, but some evidence for human exposure exists. In this review, we first summarize the data supporting a pathogenic potential of the novel chlamydiae for humans and other vertebrates and the interactions that most of these chlamydiae have with free-living amoebae. We then review the diagnostic approaches to infections potentially due to the novel chlamydiae, especially focusing on the currently available PCR-based protocols, mammalian cell culture, the amoebal coculture system, and serology.”
Zoonotic Chlamydia caviae Presenting as Community-Acquired Pneumonia
Case Study (correspondence), n=3, NEJM, 2017.
Introduction- “Chlamydia caviae is a member of the family of gram-negative intracellular bacteria Chlamydiaceae. Bacteria of this family cause a broad spectrum of diseases in animals and humans and are currently subdivided into a single genus and 11 species. Among these species, C. psittaci and C. abortus are known for their zoonotic potential, causing psittacosis and abortion, respectively, in humans. In contrast, only one case of mild conjunctivitis has previously been documented in association with C. caviae.”
Chlamydia-Like Organisms (CLOs) in Finnish Ixodes ricinus Ticks and Human Skin
Abstract- “Ticks carry several human pathogenic microbes including Borreliae and Flavivirus causing tick-born encephalitis. Ticks can also carry DNA of Chlamydia-like organisms (CLOs). The purpose of this study was to investigate the occurrence of CLOs in ticks and skin biopsies taken from individuals with suspected tick bite. DNA from CLOs was detected by pan-Chlamydiales-PCR in 40% of adult ticks from southwestern Finland. The estimated minimal infection rate for nymphs and larvae (studied in pools) was 6% and 2%, respectively. For the first time, we show CLO DNA also in human skin as 68% of all skin biopsies studied contained CLO DNA as determined through pan-Chlamydiales-PCR. Sequence analyses based on the 16S rRNA gene fragment indicated that the sequences detected in ticks were heterogeneous, representing various CLO families; whereas the majority of the sequences from human skin remained “unclassified Chlamydiales” and might represent a new family-level lineage. CLO sequences detected in four skin biopsies were most closely related to “uncultured Chlamydial bacterium clones from Ixodes ricinus ticks” and two of them were very similar to CLO sequences from Finnish ticks. These results suggest that CLO DNA is present in human skin; ticks carry CLOs and could potentially transmit CLOs to humans.”