The human microbiome project has shown a remarkable diversity of microbial ecology within the human body. The vaginal microbiota is unique in that in many women it is most often dominated by ...Lactobacillus species. However, in some women it lacks Lactobacillus spp. and is comprised of a wide array of strict and facultative anaerobes, a state that broadly correlates with increased risk for infection, disease, and poor reproductive and obstetric outcomes. Interestingly, the level of protection against infection can also vary by species and strains of Lactobacillus, and some species although dominant are not always optimal. This factors into the risk of contracting sexually transmitted infections and possibly influences the occurrence of resultant adverse reproductive outcomes such as tubal factor infertility. The composition and function of the vaginal microbiota appear to play an important role in pregnancy and fertility treatment outcomes and future research in this field will shed further translational mechanistic understanding onto the interplay of the vaginal microbiota with women's health and reproduction.
Microplastics (plastics <5 mm diameter) are at the forefront of current environmental pollution research, however, little is known about the degradation of microplastics through ingestion. Here, by ...exposing Antarctic krill (Euphausia superba) to microplastics under acute static renewal conditions, we present evidence of physical size alteration of microplastics ingested by a planktonic crustacean. Ingested microplastics (31.5 µm) are fragmented into pieces less than 1 µm in diameter. Previous feeding studies have shown spherical microplastics either; pass unaffected through an organism and are excreted, or are sufficiently small for translocation to occur. We identify a new pathway; microplastics are fragmented into sizes small enough to cross physical barriers, or are egested as a mixture of triturated particles. These findings suggest that current laboratory-based feeding studies may be oversimplifying interactions between zooplankton and microplastics but also introduces a new role of Antarctic krill, and potentially other species, in the biogeochemical cycling and fate of plastic.
In 2023, Williams and colleagues1 questioned whether the use of frequent screening for asymptomatic chlamydia and gonorrhoea in men who have sex with men should be re-evaluated. Screening and ...treatment in specific populations at risk of increased incidence and prevalence of STIs has been shown to be an effective intervention.2 However, increases in treatment are associated with increases in the acquisition of resistance.3 Therefore, reducing the frequency of screening and treatment for asymptomatic chlamydia and gonorrhoea in highly active sexual networks, such as men who have sex with men,1 is likely to have the benefit of reducing selection of antimicrobial resistance, or at least not leading to further selection, which ultimately could result in untreatable infections. ...a test would be an asset, particularly in populations and settings in which high-frequency screening is occurring, to protect against further development of antimicrobial-resistant and multidrug-resistant STIs.
There are numerous proteases of pathogenic organisms that are currently targeted for therapeutic intervention along with many that are seen as potential drug targets. This review discusses the ...chemical and biological makeup of some key druggable proteases expressed by the five major classes of disease causing agents, namely bacteria, viruses, fungi, eukaryotes, and prions. While a few of these enzymes including HIV protease and HCV NS3‐4A protease have been targeted to a clinically useful level, a number are yet to yield any clinical outcomes in terms of antimicrobial therapy. A significant aspect of this review discusses the chemical and pharmacological characteristics of inhibitors of the various proteases discussed. A total of 25 inhibitors have been considered potent and safe enough to be trialed in humans and are at different levels of clinical application. We assess the mechanism of action and clinical performance of the protease inhibitors against infectious agents with their developmental strategies and look to the next frontiers in the use of protease inhibitors as anti‐infective agents.
Genital infections with Chlamydia trachomatis continue to be a major health problem worldwide. While some individuals clear their infection (presumed to be the result of an effective Th1/interferon-γ ...response), others develop chronic infections and some are prone to repeat infections. In females in particular, chronic asymptomatic infections are common and can lead to pelvic inflammatory disease and infertility. Recent studies suggest that the genital tract microbiota could be a significant factor and explain person-to-person variation in C. trachomatis infections. One hypothesis suggests that C. trachomatis can use its trpBA genes to rescue tryptophan from indole, which is a product of anaerobic members of the genital tract microbiota. Women with particular microbiota types, such as seen in bacterial vaginosis, have increased numbers of anaerobes, and this would enable the chlamydia in these individuals to overcome the host's interferon-γ attempts to eliminate it, resulting in more repeat and/or chronic infections.
4-Chloroisocoumarin compounds have broad inhibitory properties against serine proteases. Here, we show that selected 3-alkoxy-4-chloroisocoumarins preferentially inhibit the activity of the conserved ...serine protease High-temperature requirement A of
. The synthesis of a new series of isocoumarin-based scaffolds has been developed, and their anti-chlamydial properties were investigated. The structure of the alkoxy substituent was found to influence the potency of the compounds against High-temperature requirement A, and modifications to the C-7 position of the 3-alkoxy-4-chloroisocoumarin structure attenuate anti-chlamydial properties.
There is currently no test for pelvic inflammatory disease (PID) that is non-invasive and sufficiently sensitive and specific. Clinicians must therefore diagnose PID clinically, ruling out medical ...emergencies and conducting pelvic examinations where possible. While guidelines state that clinicians should be prepared to over-diagnose PID, it remains an under-diagnosed condition, with severe reproductive health impacts when left untreated. This research is the first to consider the perspectives of end-users on the development of a diagnostic test for PID. Semi-structured live video feed online (Zoom) interviews were conducted with 11 clinicians and nine women (aged 18-30 years) in Australia to understand how a diagnostic test might be used, and what characteristics a test would need for it to be acceptable to clinicians and young women. Participants were recruited via researcher and university student networks. Reflexive thematic analysis was used to identify key themes relating to the acceptability and characteristics of a diagnostic test for PID. Seven general practitioners, four clinicians working in sexual health clinics, and nine young women (aged 21-27 years) were interviewed. Clinicians were aged between 31-58 years and were predominantly female. Clinicians recognised that the development of an accurate test to diagnose PID would be valuable to themselves and other clinicians, particularly those who lack experience diagnosing PID, and those working in certain settings, including emergency departments. They discussed how they might use a test to enhance their clinical assessment but highlighted that it would not replace clinical judgement. Clinicians also considered how a test would impact the patient experience and time to treatment, emphasising that it should be minimally invasive and have a quick turnaround time. Young women said a test would be acceptable if endorsed by a trustworthy clinician. PID remains a challenging diagnosis. Development of a minimally invasive and sufficiently accurate diagnostic test would be acceptable to young women and benefit some clinicians, although no test would completely replace an experienced clinician's judgement in making a PID diagnosis.
Devastating fires in Australia over 2019-20 decimated native fauna and flora, including koalas. The resulting population bottleneck, combined with significant loss of habitat, increases the ...vulnerability of remaining koala populations to threats which include disease. Chlamydia is one disease which causes significant morbidity and mortality in koalas. The predominant pathogenic species, Chlamydia pecorum, causes severe ocular, urogenital and reproductive tract disease. In marsupials, including the koala, gene expansions of an antimicrobial peptide family known as cathelicidins have enabled protection of immunologically naïve pouch young during early development. We propose that koala cathelicidins are active against Chlamydia and other bacteria and fungi. Here we describe ten koala cathelicidins, five of which contained full length coding sequences that were widely expressed in tissues throughout the body. Focusing on these five, we investigate their antimicrobial activity against two koala C. pecorum isolates from distinct serovars; MarsBar and IPTaLE, as well as other bacteria and fungi. One cathelicidin, PhciCath5, inactivated C. pecorum IPTaLE and MarsBar elementary bodies and significantly reduced the number of inclusions compared to the control (p<0.0001). Despite evidence of cathelicidin expression within tissues known to be infected by Chlamydia, natural PhciCath5 concentrations may be inadequate in vivo to prevent or control C. pecorum infections in koalas. PhciCath5 also displayed antimicrobial activity against fungi and Gram negative and positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Electrostatic interactions likely drive PhciCath5 adherence to the pathogen cell membrane, followed by membrane permeabilisation leading to cell death. Activity against E. coli was reduced in the presence of 10% serum and 20% whole blood. Future modification of the PhciCath5 peptide to enhance activity, including in the presence of serum/blood, may provide a novel solution to Chlamydia infection in koalas and other species.
Molecular pathogenesis of Chlamydia trachomatis Jury, Brittany; Fleming, Charlotte; Huston, Wilhelmina M ...
Frontiers in cellular and infection microbiology,
10/2023, Volume:
13
Journal Article
Peer reviewed
Open access
is a strict intracellular human pathogen. It is the main bacterial cause of sexually transmitted infections and the etiologic agent of trachoma, which is the leading cause of preventable blindness. ...Despite over 100 years since
was first identified, there is still no vaccine. However in recent years, the advancement of genetic manipulation approaches for
has increased our understanding of the molecular pathogenesis of
and progress towards a vaccine. In this mini-review, we aimed to outline the factors related to the developmental cycle phase and specific pathogenesis activity of
in order to focus priorities for future genetic approaches. We highlight the factors known to be critical for developmental cycle stages, gene expression regulatory factors, type III secretion system and their effectors, and individual virulence factors with known impacts.
The natural course of sexually transmitted infections caused by Chlamydia trachomatis varies between individuals. In addition to parasite and host effects, the vaginal microbiota might play a key ...role in the outcome of C. trachomatis infections. Interferon-gamma (IFN-γ), known for its anti-chlamydial properties, activates the expression of indoleamine 2,3-dioxygenase (IDO1) in epithelial cells, an enzyme that catabolizes the amino acid L- tryptophan into N-formylkynurenine, depleting the host cell's pool of tryptophan. Although C. trachomatis is a tryptophan auxotroph, urogenital strains (but not ocular strains) have been shown in vitro to have the ability to produce tryptophan from indole using the tryptophan synthase (trpBA) gene. It has been suggested that indole producing bacteria from the vaginal microbiota could influence the outcome of Chlamydia infection.
We used two in vitro models (treatment with IFN-γ or direct limitation of tryptophan), to study the effects of direct rescue by the addition of exogenous indole, or by the addition of culture supernatant from indole-positive versus indole-negative Prevotella strains, on the growth and infectivity of C. trachomatis. We found that only supernatants from the indole-positive strains, P. intermedia and P. nigrescens, were able to rescue tryptophan-starved C. trachomatis. In addition, we analyzed vaginal secretion samples to determine physiological indole concentrations. In spite of the complexity of vaginal secretions, we demonstrated that for some vaginal specimens with higher indole levels, there was a link to higher recovery of the Chlamydia under tryptophan-starved conditions, lending preliminary support to the critical role of the IFN-γ-tryptophan-indole axis in vivo.
Our data provide evidence for the ability of both exogenous indole as well as supernatant from indole producing bacteria such as Prevotella, to rescue genital C. trachomatis from tryptophan starvation. This adds weight to the hypothesis that the vaginal microbiota (particularly from women with lower levels of lactobacilli and higher levels of indole producing anaerobes) may be intrinsically linked to the outcome of chlamydial infections in some women.
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