The actin cytoskeleton is crucially important to maintenance of cellular structure, cell motility and endocytosis. Accordingly, bacterial pathogens often co-opt the actin-restructuring machinery of host cells to access or create a favorable environment for their own replication. The obligate intracellular organism Chlamydia trachomatis and related species exemplify this dynamic: by inducing actin polymerization at the site of pathogen-host attachment, Chlamydiae induce their own uptake by the typically non-phagocytic epithelium they infect. The interaction of chlamydial adhesins with host surface receptors has been implicated in this effect, as has the activity of the chlamydial effector TarP (translocated actin recruitment protein). Following invasion, C. trachomatis dynamically assembles and maintains an actin-rich cage around the pathogen’s membrane-bound replicative niche, the chlamydial inclusion. Through further induction of actin polymerization and modulation of the actin-crosslinking protein myosin II, C. trachomatis promotes egress from the host via extrusion of the inclusion. In this review, we present the experimental findings that inform our understanding of actin-dependent chlamydial pathogenesis, discuss lingering questions, and identify potential avenues of future study.

Koalas (Phascolarctos cinereus) are native Australian marsupials whose populations are in decline from a range of threats. Infectious diseases caused by the bacterium Chlamydia pecorum and other pathogens are of particular concern. We analysed 26 poly-A selected RNA-sequencing libraries from a data set designed to study the immune response of koalas to ocular chlamydial infection. Using virus discovery techniques, we identified the coding-complete genome sequence of a novel picorna-like virus, denoted Burpengary virus, that was most common in south-east Queensland. Notably, abundance measurements of the virus across all 26 libraries revealed an inverse relationship in prevalence with ocular disease in Koalas, suggesting that co-infection between Burpengary virus and Chlamydia pecorum is inhibited.

The impact of the cell community on its individual components in the prokaryotic realm is often overlooked. However, in the case of intracellular pathogens, where each infected cell can be considered as a single community, understanding how a population adapts to its environment to evolve and successfully propagate is key. Chlamydia infections are characterised by a silent propagation of the bacteria within individual hosts and the wider population. Chlamydia are strict intracellular pathogens residing within a specialised membrane-bound compartment called the inclusion. The life cycle of Chlamydia involves altering between the invasive elementary bodies (EBs) and replicative reticulate bodies (RBs). We have used cryo-soft X-ray tomography to observe individual inclusions, combining excellent resolution (40 nm) and large volume imaging (up to 16 µm). Combined with a semi-automated segmentation pipeline, we were able to consider each inclusion as an individual bacterial niche. Within the inclusion, we identified and classified different forms of the bacteria and confirmed the recent finding that RBs have a variety of volumes (small, large and abnormal). Moreover, we demonstrate that the proportions of these different RB forms depend on the bacterial concentration in the cell demonstrating the impact of the group on its individual component. We conclude that each inclusion operates as an autonomous community which regulates the characteristics of individual bacteria within the inclusion

Chlamydia trachomatis (CT) is an obligate intracellular bacterial pathogen known to cause trachoma, sexually transmitted infections, and reactive arthritis. The more serious sequelae of these diseases, blindness from trachoma and pelvic inflammatory disease from chlamydial STD are immunopathological responses to chronic infections. With the abundance of dendritic cells in CT infection sites and their central importance in immune regulation, the susceptibility of dendritic cells to CT infection was investigated in vitro. CT (serovar F) was grown and extracted from HeLa 229 cells for infection of human dendritic cells (DCs). Human DCs were generated from peripheral blood mononuclear cells in the presence of GM-CSF and IL-4. Infected DCs were harvested at 0, 4, 24, and 48 h after infection and immunostained. Results from fluorescence microscopy showed that DC can be infected and can support the growth of CT in vitro. Intracellular elementary and reticulate bodies of CT were detected, and reticulate bodies were shown to multiply over the 48 h-cycle in DC. At 48 h, intracellular elementary bodies were detected in some DCs. These results may provide new insights into the possible participation of DC in sustaining chronic or latent infection, or even dissemination of CT infection to other sites.

Trachsummaroma is an eye infectious disease caused by Chlamydia Trachomatis bacterium, which may lead to irreversible blindness. The disease is spread directly or indirectly by contacting a contaminated material. It can also be transmitted through the disease vector known as “Musca sorbens” or “Bazaar fly”. To curtail the spread of the disease in a population, a meaningful information on the spread and possible control of the disease is required. Mathematical modeling provides efficient tools that can be used to understand and analyze the dynamics of the disease and its control. Several compartmental epidemic models have been proposed in the literature to study the dynamics of trachoma; including SI, SIR and SEIR. However, majority of the existing trachoma models consider only person to person transmission. Thus, the information provided by such models is insufficient since they did not capture the disease vector transmission. The current study proposed a novel SEIR-SEI model that consider both person-person and vector transmission dynamics. The threshold quantity, basic reproduction number R0 is obtained using the next generation matrix, and it was proved that the disease-free equilibrium is asymptotically stable when R0 < 1, and the endemic equilibrium is globally asymptotically stable when R0 > 1. Some simulation results with the aid of mesh plots for the reproductive number as a function of two different biological parameters were obtained. Furthermore, a comprehensive sensitivity analysis is conducted to identify the influence of the individual parameters on the R0. Numerical results show that the vector contact rate has the highest sensitivity with respect to R0, and the value of R0 increases with increase in, hence, the disease can be controlled by decreasing the vector contact rate. Similarly, improving the rate of environmental hygiene and facial cleanliness will decrease the size of R0 and result in the declination of the disease transmission. Moreover, a detailed parameter estimation of the model parameters and model fitting was presented with the use of field data cases from Northern Nigeria using least-square fitting method. The study provides alternative tools that can be used for planning trachoma control program to achieve global eradication of trachoma as a public heath challenge as targeted by WHO in 2030.

We investigated the effect of C. psittaci and H9N2 coinfection on HD11 cells in vitro, expecting to find the potential pathogenesis of airsacculitis caused by co-infection of C. psittaci and H9N2. HD11 cells were infected with C. psittaci and/or H9N2 in a different order, and effects of the co-infection on iNOS expression and activity, NO synthesis, cell phagocytosis, and cytokines levels in HD11 cells were determined. Results showed that C. psittaci and H9N2 can significantly aggravate the mortality of HD11 cells compared to the effects of infection with one pathogen alone. In addition, infection with C. psittaci can increase the replication of H9N2 in HD11 cells, whereas decrease the iNOS level and enzyme activity as well as NO concentration of HD11 cells by H9N2 infection. We also found that C. psittaci infection alone can significantly decrease the phagocytosis of HD11 cells, compared to H9N2 infection alone. Furthermore, infection with C. psittaci can increase the mRNA expressions of type Th2 cytokines IL-6 and IL-10 of HD11 cells by H9N2 infection. All the above data indicated that primary C. psittaci infection is able to aggravate H9N2 invasion by down-regulating functions of HD11 cells

Unidentified abortion, of which leptospirosis, brucellosis and ovine enzootic abortion are important factors, is the main cause of disease spread between animals and humans in all agricultural systems in most developing countries. Although there are well-defined risk factors for these diseases, these characteristics do not represent the prevalence of the disease in different regions. This study predicts the unidentified abortion burden from multi-microorganisms in ewes based on artificial neural networks approach and GLM. Methods: A two-stage cluster survey design was conducted to estimate the seroprevalence of abortifacient microorganisms, and to identify putative factors of infectious abortion. Results: Overall seroprevalence of Brucella was 70.7%, while Leptospira spp. was 55.2%, C. abortus 21.9% and B. ovis 7.4%. Serological detection with the 4 abortion-causing microorganisms was determined only in 0.87% of sheep sampled. The best GLM is integrated by serological detection of serovar Hardjo and Brucella ovis in animals of the slopes with elevation between 2600 to 2800 meters above sea level from municipality of Xalatlaco, as well water supply, sheep pen built with materials of metal grids and untreated wood, with dirt and concrete floors, and bed of straw that remained independently associated with infectious abortion in ewes. Approximately 80% of those respondents did not wear gloves or masks to prevent the transmission of the abortifacient zoonotic microorganisms. Conclusions: Sensitizing stakeholders on good agricultural practices could improve public health surveillance. Further studies on the effect of animal-human transmission in such a setting are worthwhile to further support the One Health initiative.

Chlamydia trachomatis (Ct) infections are the most common sexually-transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we use the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial protease-like activity factor (CPAF) protein. We tested two weekly administration options – twice intranasal (IN) followed by twice intramuscular (IM), or twice IM followed by twice IN. We assessed the humoral immune response not only in serum by CPAF-specific IgG including antibody avidity determination but also in cervical and rectal swabs by CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed upon in vitro CPAF-restimulation via IFN-γ and IL-17 ELISpots as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response: Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response by CD4 T cells. In the IM/IN vaccinated pigs, these cells also significantly downregulated their CCR7 expression – a sign for differentiation into peripheral tissue homing effector/ memory cells. Conclusively, this study demonstrates strong immunogenicity of the IM/IN administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.

There is now considerable evidence that several infectious agents (viruses, bacteria, or parasites) may play a contributing role in the development of Alzheimer’s disease (AD). The six primary suspects are herpes viruses, spirochetal bacteria, Chlamydia pneumoniae, Porphyromonas gingivalis, mycobacteria, and toxoplasma parasites. Also, some of the antimicrobial and antiviral agents that are used to treat them have shown promise for AD interventions. I describe this evidence and assert it is now time to accelerate clinical trials of these existing drugs, already federally approved, to determine if such treatments can delay, halt, or reverse AD.