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From 1 January 2022 to 31 May 2024, the World Health Organization (WHO) reported 97,745 laboratory-confirmed Mpox cases, including 203 deaths, across 116 countries. Despite a 2.3% decrease in new cases in May 2024 compared to April 2024, significant regional variations persist. The African Region reported the highest proportion of new cases, while other regions experienced mixed trends. Phylogenomic analyses of the Mpox virus Clade IIb lineage B.1 reveal stable genetic variability with minimal diversification. The Bayesian Skyline Plot indicates a generally stable viral population size with a modest peak in late 2023, followed by a decline. In general, the data indicate that the MPXV outbreak is primarily localized within a few consistent geographic clusters. The virus's evolution is relatively slow, as indicated by its stable genetic variability, and Clade IIb lineage B.1 does not currently show signs of rapid genetic changes or population growth. The current low level of genetic diversity should not lead to complacency. Ongoing genomic surveillance is essential for effective outbreak management and understanding. This monitoring is crucial for identifying any shifts in the virus's behavior or transmission, allowing for prompt public health responses and adjustments. In addition, continued vigilance is necessary to detect any new variants that might influence the outbreak's trajectory. [ABSTRACT FROM AUTHOR]

Background: The contribution of gut microbiota to the pathogenesis of polycystic ovary syndrome (PCOS) is controversial. The causal relationship to this question is worth an in-depth comprehensive of known single nucleotide polymorphisms associated with gut microbiota. Methods: We conducted bidirectional Mendelian randomization (MR) utilizing instrumental variables associated with gut microbiota (N = 18,340) from MiBioGen GWAS to assess their impact on PCOS risk in the FinnGen GWAS (27,943 PCOS cases and 162,936 controls). Two-sample MR using inverse variance weighting (IVW) was undertaken, followed by the weighted median, weighted mode, and MR-Egger regression. In a subsample, we replicated our findings using themeta-analysis PCOS consortium (10,074 cases and 103,164 controls) from European ancestry. Results: IVWMR results suggested that six gut microbiota were causally associated with PCOS features. After adjusting BMI, SHBG, fasting insulin, testosterone, and alcohol intake frequency, the effect sizes were significantly reduced. Reverse MR analysis revealed that the effects of PCOS features on 13 gut microbiota no longer remained significant after sensitivity analysis and Bonferroni corrections. MR replication analysis was consistent and the results suggest that gut microbiota was likely not an independent cause of PCOS. Conclusion: Our findings did not support the causal relationships between the gut microbiota and PCOS features at the genetic level. More comprehensive genome-wide association studies of the gut microbiota and PCOS are warranted to confirm their genetic relationship. Declaration: This study contains 3533 words, 0 tables, and six figures in the text as well as night supplementary files and 0 supplementary figures in the Supplementary material. [ABSTRACT FROM AUTHOR]

The cultivation of cyanobacteria by exploiting available in situ resources represents a possible way to supply food and oxygen to astronauts during long-term crewed missions on Mars. Here, we evaluated the possibility of cultivating the extremophile cyanobacterium Chroococcidiopsis thermalis CCALA 050 under operating conditions that should occur within a dome hosting a recently patented process to produce nutrients and oxygen on Mars. The medium adopted to cultivate this cyanobacterium, named Martian medium, was obtained using a mixture of regolith leachate and astronauts' urine simulants that would be available in situ resources whose exploitation could reduce the mission payload. The results demonstrated that C. thermalis can grow in such a medium. For producing high biomass, the best medium consisted of specific percentages (40%vol) of Martian medium and a standard medium (60%vol). Biomass produced in such a medium exhibits excellent antioxidant properties and contains significant amounts of pigments. Lipidomic analysis demonstrated that biomass contains strategic lipid classes able to help the astronauts facing the oxidative stress and inflammatory phenomena taking place on Mars. These characteristics suggest that this strain could serve as a valuable nutritional resource for astronauts. [ABSTRACT FROM AUTHOR]

The XBB.1.16 SARS-CoV-2 variant, also known as Arcturus, is a recent descendant lineage of the recombinant XBB (nicknamed Gryphon). Compared to its direct progenitor, XBB.1, XBB.1.16 carries additional spike mutations in key antigenic sites, potentially conferring an ability to evade the immune response compared to other circulating lineages. In this context, we conducted a comprehensive genome-based survey to gain a detailed understanding of the evolution and potential dangers of the XBB.1.16 variant, which became dominant in late June. Genetic data indicates that the XBB.1.16 variant exhibits an evolutionary background with limited diversification, unlike dangerous lineages known for rapid changes. The evolutionary rate of XBB.1.16, which amounts to 3.95 × 10−4 subs/site/year, is slightly slower than that of its direct progenitors, XBB and XBB.1.5, which have been circulating for several months. A Bayesian Skyline Plot reconstruction suggests that the peak of genetic variability was reached in early May 2023, and currently, it is in a plateau phase with a viral population size similar to the levels observed in early March. Structural analyses indicate that, overall, the XBB.1.16 variant does not possess structural characteristics markedly different from those of the parent lineages, and the theoretical affinity for ACE2 does not seem to change among the compared variants. In conclusion, the genetic and structural analyses of SARS-CoV-2 XBB.1.16 do not provide evidence of its exceptional danger or high expansion capability. Detected differences with previous lineages are probably due to genetic drift, which allows the virus constant adaptability to the host, but they are not necessarily connected to a greater danger. Nevertheless, continuous genome-based monitoring is essential for a better understanding of its descendants and other lineages. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 EG.5 lineage is the latest variant under monitoring, and it is generating significant concern due to its recent upward trend in prevalence. Our aim was to gain insights into this emerging lineage and offer insights into its actual level of threat. Both genetic and structural data indicate that this novel variant presently lacks substantial evidence of having a high capacity for widespread transmission. Their viral population sizes expanded following a very mild curve and peaked several months after the earliest detected sample. Currently, neither the viral population size of EG.5 nor that of its first descendant is increasing. The genetic variability appear to be flattened, as evidenced by its relatively modest evolutionary rate (9.05 × 10−4 subs/site/year). As has been observed with numerous prior variants, attributes that might theoretically provide advantages seem to stem from genetic drift, enabling the virus to continually adjust to its host, albeit without a clear association with enhanced dangerousness. These findings further underscore the necessity for ongoing genome‐based monitoring, ensuring preparedness and a well‐documented understanding of the unfolding situation. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis is a pathogenic protozoan diffused worldwide capable of infecting the urogenital tract in humans, causing trichomoniasis. One of its most intriguing aspects is the ability to establish a close relationship with endosymbiotic microorganisms: the unique association of T. vaginalis with the bacterium Mycoplasma hominis represents, to date, the only example of an endosymbiosis involving two true human pathogens. Since its discovery, several aspects of the symbiosis between T. vaginalis and M. hominis have been characterized, demonstrating that the presence of the intracellular guest strongly influences the pathogenic characteristics of the protozoon, making it more aggressive towards host cells and capable of stimulating a stronger proinflammatory response. The recent description of a further symbiont of the protozoon, the newly discovered non-cultivable mycoplasma Candidatus Mycoplasma girerdii, makes the picture even more complex. This review provides an overview of the main aspects of this complex microbial consortium, with particular emphasis on its effect on protozoan pathobiology and on the interplays among the symbionts. [ABSTRACT FROM AUTHOR]

The article discusses the emergence of the SARS-CoV-2 HV.1 lineage, also known as EG.5.1.6.1 or XBB.1.9.2.5.1. This variant is spreading rapidly in the United States and has become the most prevalent lineage, causing concerns in the community. The HV.1 lineage has several spike mutations, including Q52H, F157L, and L452R, which may compromise the efficacy of previously acquired neutralizing antibodies. The L452R mutation, in particular, has been observed in other variants and may increase the virus's ability to bind to human cells. However, the current evidence suggests that the HV.1 lineage does not pose a major public health risk. Ongoing research is needed to understand the impact of these mutations and guide interventions. [Extracted from the article]

Recombination events are very common and represent one of the primary drivers of RNA virus evolution. The XBF SARS-CoV-2 lineage is one of the most recently generated recombinants during the COVID-19 pandemic. It is a recombinant of BA.5.2.3 and BA.2.75.3, both descendants of lineages that caused many concerns (BA.5 and BA.2.75, respectively). Here, we performed a genomic survey focused on comparing the recombinant XBF with its parental lineages to provide a comprehensive assessment of the evolutionary potential, epidemiological trajectory, and potential risks. Genetic analyses indicated that although XBF initially showed the typical expansion depicted by a steep curve, causing several concerns, currently there is no indication of significant expansion potential or a contagion rate surpassing that of other currently active or previously prevalent lineages. BSP indicated that the peak has been reached around 19 October 2022 and then the genetic variability suffered slight oscillations until early 5 March 2023 when the population size reduced for the last time starting its last plateau that is still lasting. Structural analyses confirmed its reduced potential, also indicating that properties of NTDs and RBDs of XBF and its parental lineages present no significant difference. Of course, cautionary measures must still be taken and genome-based monitoring remains the best tool for detecting any important changes in viral genome composition. [ABSTRACT FROM AUTHOR]

The SARS‐CoV‐2 BF.7 variant represents one of the most recent subvariant under monitoring. At the beginning of the 2023 it caused several concerns especially in Asia because of a resurge in COVID‐19 cases. Here we perform a genome‐based integrative approach on SARS‐CoV‐2 BF.7 to shed light on this emerging lineage and produce some consideration on its real dangerousness. Both genetic and structural data suggest that this new variant currently does not show evidence of an high expansion capability. It is very common in Asia, but it appears less virulent than other Omicron variants as proved by its relatively low evolutionary rate (5.62 × 10−4 subs/sites/years). The last plateau has been reached around December 14, 2022 and then the genetic variability, and thus the viral population size, no longer increased. As already seen for several previous variants, the features that may be theoretically related to advantages are due to genetic drift that allows to the virus a constant adaptability to the host, but is not strictly connected to a fitness advantage. These results have further pointed that the genome‐based monitoring must continue uninterruptedly to be prepared and well documented on the real situation. [ABSTRACT FROM AUTHOR]

Since the beginning of the pandemic, the generation of new variants periodically recurs. The XBB.1.5 SARS-CoV-2 variant is one of the most recent. This research was aimed at verifying the potential hazard of this new subvariant. To achieve this objective, we performed a genome-based integrative approach, integrating results from genetic variability/phylodynamics with structural and immunoinformatic analyses to obtain as comprehensive a viewpoint as possible. The Bayesian Skyline Plot (BSP) shows that the viral population size reached the plateau phase on 24 November 2022, and the number of lineages peaked at the same time. The evolutionary rate is relatively low, amounting to 6.9 × 10−4 subs/sites/years. The NTD domain is identical for XBB.1 and XBB.1.5 whereas their RBDs only differ for the mutations at position 486, where the Phe (in the original Wuhan) is replaced by a Ser in XBB and XBB.1, and by a Pro in XBB.1.5. The variant XBB.1.5 seems to spread more slowly than sub-variants that have caused concerns in 2022. The multidisciplinary molecular in-depth analyses on XBB.1.5 performed here does not provide evidence for a particularly high risk of viral expansion. Results indicate that XBB.1.5 does not possess features to become a new, global, public health threat. As of now, in its current molecular make-up, XBB.1.5 does not represent the most dangerous variant. [ABSTRACT FROM AUTHOR]

Recombination is the main contributor to RNA virus evolution, and SARS‐CoV‐2 during the pandemic produced several recombinants. The most recent SARS‐CoV‐2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM.1.1.1. Here we performed a genome‐based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub‐lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, at present XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome‐based monitoring must continue uninterrupted to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability. [ABSTRACT FROM AUTHOR]

The BQ.1 SARS-CoV-2 variant, also known as Cerberus, is one of the most recent Omicron descendant lineages. Compared to its direct progenitor BA.5, BQ.1 has some additional spike mutations in some key antigenic sites, which confer further immune escape ability over other circulating lineages. In such a context, here, we perform a genome-based survey aimed at obtaining a complete-as-possible nuance of this rapidly evolving Omicron subvariant. Genetic data suggest that BQ.1 represents an evolutionary blind background, lacking the rapid diversification that is typical of a dangerous lineage. Indeed, the evolutionary rate of BQ.1 is very similar to that of BA.5 (7.6 × 10−4 and 7 × 10−4 subs/site/year, respectively), which has been circulating for several months. The Bayesian Skyline Plot reconstruction indicates a low level of genetic variability, suggesting that the peak was reached around 3 September 2022. Concerning the affinity for ACE2, structure analyses (also performed by comparing the properties of BQ.1 and BA.5 RBD) indicate that the impact of the BQ.1 mutations may be modest. Likewise, immunoinformatic analyses showed moderate differences between the BQ.1 and BA5 potential B-cell epitopes. In conclusion, genetic and structural analyses on SARS-CoV-2 BQ.1 suggest no evidence of a particularly dangerous or high expansion capability. Genome-based monitoring must continue uninterrupted for a better understanding of its descendants and all other lineages. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis is the causative agent of one of the most widespread sexually transmitted diseases in the world. The adhesion of the parasite to the vaginal epithelial cells is mediated by specific proteins and by a complex glycan structure, the lipoglycan (TvLG), which covers the pathogen surface. L-rhamnose is an important component of TvLG, comprising up to 40% of the monosaccharides. Thus, the inhibition of its production could lead to a severe alteration in the TvLG structure, making the L-rhamnose biosynthetic pathway an attractive pharmacologic target. We report the identification and characterization of the first committed and limiting step of the L-rhamnose biosynthetic pathway, UDP-D-glucose 4,6-dehydratase (UGD, EC 4.2.1.76). The enzyme shows a strong preference for UDP-D-glucose compared to dTDP-D-glucose; we propose that the mechanism underlying the higher affinity for the UDP-bound substrate is mediated by the differential recognition of ribose versus the deoxyribose of the nucleotide moiety. The identification of the enzymes responsible for the following steps of the L-rhamnose pathway (epimerization and reduction) was more elusive. However, sequence analyses suggest that in T. vaginalis L-rhamnose synthesis proceeds through a mechanism different from the typical eukaryotic pathways, displaying intermediate features between the eukaryotic and prokaryotic pathways and involving separate enzymes for the epimerase and reductase activities, as observed in bacteria. Altogether, these results form the basis for a better understanding of the formation of the complex glycan structures on TvLG and the possible use of L-rhamnose biosynthetic enzymes for the development of selective inhibitors. [ABSTRACT FROM AUTHOR]

Monkeypox is caused by a sylvatic, double-stranded DNA zoonotic virus. Since 1 January 2022, monkeypox cases have been reported to WHO from 106 Member States across six WHO regions, and as of 2 October 2022, a total of 68,900 confirmed cases, including 25 deaths, occurred. Here, by using a whole genome approach, we perform a genetic and phylodynamic survey of the monkeypox virus Clade IIb B.1, which is the lineage causing the current multi-country outbreak. Results suggest that outbreaks seem to be isolated and localized in several epidemic clusters with geographic consistency. Currently, monkeypox appears to be a virus with a flattened genetic variability in terms of evolutionary path, with a very slow rate of growth in the population size. This scenario confirms that the monkeypox virus lacks the evolutionary advantage, given by the high level of mutation rate, which is very strong in RNA viruses. Of course, constant genome-based monitoring must be performed over time in order to detect the change in its genetic composition, if any. [ABSTRACT FROM AUTHOR]

Nowadays, fungal infections increase, and the demand of novel antifungal agents is constantly rising. In the present study, silver, titanium dioxide, cobalt (II) hydroxide and cobalt (II,III) oxide nanomaterials have been synthesized from Spirulina platensis extract. The synthesis mechanism has been studied using GCMS and FTIR thus confirming the involvement of secondary metabolites, mainly amines. The obtained products have been analysed using XRD, SEM, TGA and zeta potential techniques. The findings revealed average crystallite size of 15.22 nm with 9.72 nm for oval-shaped silver nanoparticles increasing to 26.01 nm and 24.86 nm after calcination and 4.81 nm for spherical-shaped titanium dioxide nanoparticles which decreased to 4.62 nm after calcination. Nanoflake shape has been observed for cobalt hydroxide nanomaterials and for cobalt (II, III) oxide with crystallite size of 3.52 nm and 13.28 nm, respectively. Silver nanoparticles showed the best thermal and water dispersion stability of all the prepared structures. Once subjected to three different Candida species (C. albicans, C. glabrata, and C. krusei) silver nanoparticles and cobalt (II) hydroxide nanomaterials showed strong antifungal activity at 50 μg/mL with minimum inhibitory concentration (MIC) values. After light exposition, MIC values for nanomaterials decreased (to 12.5 μg/mL) for C. krusei and increased (100 μg/mL) for C. albicans and C. glabrata. [ABSTRACT FROM AUTHOR]

Trichomoniasis, the most common non-viral sexually transmitted infection worldwide, is caused by the protozoon Trichomonas vaginalis. The 5- nitroimidazole drugs, of which metronidazole is the most prescribed, are the only effective drugs to treat trichomoniasis. Resistance against metronidazole is increasingly reported among T. vaginalis isolates. T. vaginalis can establish an endosymbiosis with two Mycoplasma species, Mycoplasma hominis and Candidatus Mycoplasma girerdii, whose presence has been demonstrated to influence several aspects of the protozoan pathobiology. The role of M. hominis in T. vaginalis resistance to metronidazole is controversial, while the influence of Ca. M. girerdii has never been investigated. In this work, we investigate the possible correlation between the presence of Ca. M. girerdii and/or M. hominis and the in vitro drug susceptibility in a large group of T. vaginalis isolated in Italy and in Vietnam. We also evaluated, via RNA-seq analysis, the expression of protozoan genes involved in metronidazole resistance in a set of syngenic T. vaginalis strains, differing only for the presence/absence of the two Mycoplasmas. Our results show that the presence of M. hominis significantly increases the sensitivity to metronidazole in T. vaginalis and affects gene expression. On the contrary, the symbiosis with Candidatus Mycoplasma girerdii seems to have no effect on metronidazole resistance in T. vaginalis. [ABSTRACT FROM AUTHOR]

Abstract Background Trichomonas vaginalis is the most common non-viral human sexually transmitted pathogen and importantly, contributes to facilitating the spread of HIV. Yet very little is known about its surface and secreted proteins mediating interactions with, and permitting the invasion and colonisation of, the host mucosa. Initial annotations of T. vaginalis genome identified a plethora of candidate extracellular proteins. Results Data mining of the T. vaginalis genome identified 911 BspA-like entries (TvBspA) sharing TpLRR-like leucine-rich repeats, which represent the largest gene family encoding potential extracellular proteins for the pathogen. A broad range of microorganisms encoding BspA-like proteins was identified and these are mainly known to live on mucosal surfaces, among these T. vaginalis is endowed with the largest gene family. Over 190 TvBspA proteins with inferred transmembrane domains were characterised by a considerable structural diversity between their TpLRR and other types of repetitive sequences and two subfamilies possessed distinct classic sorting signal motifs for endocytosis. One TvBspA subfamily also shared a glycine-rich protein domain with proteins from Clostridium difficile pathogenic strains and C. difficile phages. Consistent with the hypothesis that TvBspA protein structural diversity implies diverse roles, we demonstrated for several TvBspA genes differential expression at the transcript level in different growth conditions. Identified variants of repetitive segments between several TvBspA paralogues and orthologues from two clinical isolates were also consistent with TpLRR and other repetitive sequences to be functionally important. For one TvBspA protein cell surface expression and antibody responses by both female and male T. vaginalis infected patients were also demonstrated. Conclusions The biased mucosal habitat for microbial species encoding BspA-like proteins, the characterisation of a vast structural diversity for the TvBspA proteins, differential expression of a subset of TvBspA genes and the cellular localisation and immunological data for one TvBspA; all point to the importance of the TvBspA proteins to various aspects of T. vaginalis pathobiology at the host-pathogen interface.

Ever since the publication of the seminal paper by Lynn Margulis in 1967 proposing the theory of the endosymbiotic origin of organelles, the study of the symbiotic relationships between unicellular eukaryotes and prokaryotes has received ever-growing attention by microbiologists and evolutionists alike. While the evolutionary significance of the endosymbiotic associations within protists has emerged and is intensively studied, the impact of these relationships on human health has been seldom taken into account. Microbial endosymbioses involving human eukaryotic pathogens are not common, and the sexually transmitted obligate parasite Trichomonas vaginalis and the free-living opportunistic pathogen Acanthamoeba represent two unique cases in this regard, to date. The reasons of this peculiarity for T. vaginalis and Acanthamoeba may be due to their lifestyles, characterized by bacteria-rich environments. However, this characteristic does not fully explain the reason why no bacterial endosymbiont has yet been detected in unicellular eukaryotic human pathogens other than in T. vaginalis and Acanthamoeba , albeit sparse and poorly investigated examples of morphological identification of bacteria-like microorganisms associated with Giardia and Entamoeba were reported in the past. In this review article we will present the body of experimental evidences revealing the profound effects of these examples of protist/bacteria symbiosis on the pathogenesis of the microbial species involved, and ultimately their impact on human health. [ABSTRACT FROM AUTHOR]

Pore-forming proteins (PFPs) are a group of functionally versatile molecules distributed in all domains of life, and several microbial pathogens notably use members of this class of proteins as cytotoxic effectors. Among pathogenic protists, Entamoeba histolytica , and Naegleria fowleri display a range of pore-forming toxins belonging to the Saposin-Like Proteins (Saplip) family: Amoebapores and Naegleriapores. Following the genome sequencing of Trichomonas vaginalis , we identified a gene family of 12 predicted saposin-like proteins (TvSaplips): this work focuses on investigating the potential role of TvSaplips as cytopathogenetic effectors. We provide evidence that TvSaplip12 gene expression is potently upregulated upon T. vaginalis contact with target cells. We cloned and expressed recombinant TvSaplip12 in planta and we demonstrate haemolytic, cytotoxic, and bactericidal activities of rTvSaplip12 in vitro. Also, evidence for TvSaplip subcellular discrete distribution in cytoplasmic granules is presented. Altogether, our results highlight the importance of TvSaplip in T. vaginalis pathogenesis, depicting its involvement in the cytolytic and bactericidal activities during the infection process, leading to predation on host cells and resident vaginal microbiota for essential nutrients acquisition. This hence suggests a potential key role for TvSaplip12 in T. vaginalis pathogenesis as a candidate Trichopore. [ABSTRACT FROM AUTHOR]

The protozoon Trichomonas vaginalis is responsible for trichomoniasis, a common sexually transmitted infection associated with an increased risk of HIV infection and adverse pregnancy outcomes. The protozoon has the surprising ability to establish a symbiotic relationship with other microorganisms. In fact, most T.vaginalis isolates intracellularly host the vaginal bacterium Mycoplasma hominis and can harbor up to four dsRNA viruses. Moreover, a novel Mycoplasma species named Ca. Mycoplasma girerdii has been recently described as associated with trichomonad cells. Trichomonas vaginalis colonizes the human vagina and its presence causes profound alterations of the resident microbiota, leading to dysbiosis. In healthy women, vaginal microbiota is characterized by the presence of a complex population of aerobic and anaerobic microorganisms living in a physiologically dynamic system dominated by bacteria of the genera Lactobacillus. The most common microbial vaginal imbalance is bacterial vaginosis, a polymicrobial disease associated with several adverse reproductive outcomes and increased risk of HIV infection. Here, we review the current knowledge regarding the interactions between both T.vaginalis and M.hominis and the vaginal microbiota, and we discuss the possibility of a cooperation between T.vaginalis and its symbionts in the development of vaginal dysbiosis. [ABSTRACT FROM AUTHOR]

Mycoplasma lipoproteins play a relevant role in pathogenicity and directly interact with the host immune system. Among human mycoplasmas, Mycoplasma hominis is described as a commensal bacterium that can be associated with a number of genital and extragenital conditions. Mechanisms of M. hominis pathogenicity are still largely obscure, and only a limited number of proteins have been associated with virulence. The current study focused on investigating the role of MHO_0730 as a virulence factor and demonstrated that MHO_0730 is a surface lipoprotein, potentially expressed in vivo during natural infection, acting both as a nuclease with its amino acidic portion and as a potent inducer of Neutrophil extracellular trapsosis with its N-terminal lipid moiety. Evidence for M. hominis neutrophil extracellular trap escape is also presented. Results highlight the relevance of MHO_0730 in promoting infection and modulation and evasion of innate immunity and provide additional knowledge on M. hominis virulence and survival in the host. [ABSTRACT FROM AUTHOR]

The flagellated protozoon Trichomonas vaginalis, responsible for trichomoniasis, can establish a symbiotic relationship with the bacterium Mycoplasma hominis and can harbor double-stranded RNA Trichomonasvirus (TVV). In this study, we investigated by real-time PCR the prevalence of the four TVVs and of M. hominis among 48 T. vaginalis strains isolated in Italy, and we evaluated a possible association with metronidazole resistance. Fifty percent of the analyzed trichomonad strains tested positive for at least one TVV T. vaginalis, with TVV2 being the most prevalent, followed by TVV1 and TVV3. Two T. vaginalis strains were infected by TVV4, detected in Europe for the first time. Interestingly, we found more than one TVV species in 75% of positive trichomonad strains. M. hominis was present in 81.25% of T. vaginalis isolates tested, and no statistically significant association was observed with the infection by any TVV. Metronidazole sensitivity of T. vaginalis isolates was evaluated in vitro, and no correlation was observed between minimal lethal concentration and the presence of TVVs. This is the first report on TVV infection of T. vaginalis in Italy. Even if no association of TVV positive isolates with the presence of the symbiont M. hominis or with metronidazole resistance was observed, further studies are needed to shed light on the effective role of infecting microorganisms on the pathophysiology of T. vaginalis. [ABSTRACT FROM AUTHOR]

The diagnosis of bloodstream infections (BSIs) still relies on blood culture (BC), but low turnaround times may hinder the early initiation of an appropriate antimicrobial therapy, thus increasing the risk of infection-related death. We describe a direct and rapid multiplex PCR-based assay capable of detecting and identifying 16 bacterial and four Candida species, as well as three antibiotic-resistance determinants, in uncultured samples. Using whole-blood samples spiked with microorganisms at low densities, we found that the MicrobScan assay had a mean limit of detection of 15.1 ± 3.3 CFU of bacteria/ Candida per ml of blood. When applied to positive BC samples, the assay allowed the sensitive and specific detection of BSI pathogens, including bla KPC-, mecA -, or vanA / vanB -positive bacteria. We evaluated the assay using prospectively collected blood samples from patients with suspected BSI. The sensitivity and specificity were 86.4 and 97.0%, respectively, among patients with positive BCs for the microorganisms targeted by the assay or patients fulfilling the criteria for infection. The mean times to positive or negative assay results were 5.3 ± 0.2 and 5.1 ± 0.1 h, respectively. Fifteen of 20 patients with MicrobScan assay-positive/BC-negative samples were receiving antimicrobial therapy. In conclusion, the MicrobScan assay is well suited to complement current diagnostic methods for BSIs. [ABSTRACT FROM AUTHOR]

Background: In Vietnam, a rapid decline of P. falciparum malaria cases has been documented in the past years, the number of Plasmodium falciparum malaria cases has rapidly decreased passing from 19.638 in 2012 to 4.073 cases in 2016. Concomitantly, the spread of artemisinin resistance markers is raising concern on the future efficacy of the ACTs. An evaluation of the clinical impact of the artemisinin resistance markers is therefore of interest. Methods: The clinical effectiveness of dihydroartemisinin-piperaquine therapy (DHA-PPQ) has been evaluated in three districts characterized by different rates of ART resistance markers: K13(C580Y) mutation and delayed parasite clearance on day 3 (DPC3). Patients were stratified in 3 groups a) no markers, b) one marker (suspected resistance), c) co-presence of both markers (confirmed resistance). In the studied areas, the clinical effectiveness of DHA-PPQ has been estimated as malaria recrudescence within 60 days. Results: The rate of K13(C580Y) ranged from 75.8% in Krong Pa to 1.2% in Huong Hoa district. DPC3 prevalence was higher in Krong Pa than in Huong Hoa (86.2% vs 39.3%). In the two districts, the prevalence of confirmed resistance was found in 69.0% and 1.2% of patients, respectively. In Thuan Bac district, we found intermediate prevalence of confirmed resistance. Treatment failure was not evidenced in any district. PPQ resistance was not evidenced. Confirmed resistance was associated to the persistence of parasites on day 28 and to 3.4-fold higher parasite density at diagnosis. The effectiveness of malaria control strategies was very high in the studied districts. Conclusion: No treatment failure has been observed in presence of high prevalence of ART resistance and in absence of PPQ resistance. K13(C580Y) was strongly associated to higher parasitemia at admission, on days 3 and 28. Slower parasite clearance was also observed in younger patients. [ABSTRACT FROM AUTHOR]

Mycoplasma hominis is considered an opportunistic pathogen able to colonize the lower urogenital tract; in females the infection is associated with severe pregnancy and postpartum complications, including abortion, endometritis, preterm delivery, and low birth weight. Molecular mechanisms of pathogenicity and virulence effectors remain poorly characterized. A number of studies in the last decade have demonstrated that M. hominis can establish an endosymbiotic relationship with Trichomonas vaginalis, a urogenital parasitic protozoon, also associated with adverse pregnancy outcomes. Recently, two bacterial genes (alr and goiB) associated with amniotic cavity invasion and a single gene (goiC) associated with intra-amniotic infections and high risk of preterm delivery have been identified in M. hominis isolated from a group of pregnant patients. In this work we demonstrate that a high number of M. hominis intracellularly associated with T. vaginalis have goiC gene, in association with alr and goiB. In addition, we demonstrate that metronidazole treatment of M. hominis-infected T. vaginalis allows delivering viable intracellular goiC positive M. hominis from antibiotic-killed protozoa and that free M. hominis can infect human cell cultures. Results suggest that molecular diagnostic strategies to identify both pathogens and their virulence genes should be adopted to prevent severe complications during pregnancy. [ABSTRACT FROM AUTHOR]

The human infective parasite Trichomonas vaginalis causes the most prevalent nonviral sexually transmitted infection worldwide. Infections in men may result in colonization of the prostate and are correlated with increased risk of aggressive prostate cancer. We have found that T. vaginalis secretes a protein, T. vaginalis macrophage migration inhibitory factor (TvMIF), that is 47% similar to human macrophage migration inhibitory factor (HuMIF), a proinflammatory cytokine. Because HuMIF is reported to be elevated in prostate cancer and inflammation plays an important role in the initiation and progression of cancers, we have explored a role for TvMIF in prostate cancer. Here, we show that TvMIF has tautomerase activity, inhibits macrophage migration, and is proinflammatory. We also demonstrate that TvMIF binds the human CD74 MIF receptor with high affinity, comparable to that of HuMIF, which triggers activation of ERK, Akt, and Bcl-2 associated death promoter phosphorylation at a physiologically relevant concentration (1 ng/mL, 80 pM). TvMIF increases the in vitro growth and invasion through Matrigel of benign and prostate cancer cells. Sera from patients infected with T. vaginalis are reactive to TvMIF, especially in males. The presence of anti-TvMIF antibodies indicates that TvMIF is released by the parasite and elicits host immune responses during infection. Together, these data indicate that chronic T. vaginalis infections may result in TvMIF-driven inflammation and cell proliferation, thus triggering pathways that contribute to the promotion and progression of prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection world-wide. Despite its prevalence, little is known about the genetic diversity and population structure of this haploid parasite due to the lack of appropriate tools. The development of a panel of microsatellite makers and SNPs from mining the parasite's genome sequence has paved the way to a global analysis of the genetic structure of the pathogen and association with clinical phenotypes. Methodology/Principal Findings: Here we utilize a panel of T. vaginalis-specific genetic markers to genotype 235 isolates from Mexico, Chile, India, Australia, Papua New Guinea, Italy, Africa and the United States, including 19 clinical isolates recently collected from 270 women attending New York City sexually transmitted disease clinics. Using population genetic analysis, we show that T. vaginalis is a genetically diverse parasite with a unique population structure consisting of two types present in equal proportions world-wide. Parasites belonging to the two types (type 1 and type 2) differ significantly in the rate at which they harbor the T. vaginalis virus, a dsRNA virus implicated in parasite pathogenesis, and in their sensitivity to the widely-used drug, metronidazole. We also uncover evidence of genetic exchange, indicating a sexual life-cycle of the parasite despite an absence of morphologically-distinct sexual stages. Conclusions/Significance: Our study represents the first robust and comprehensive evaluation of global T. vaginalis genetic diversity and population structure. Our identification of a unique two-type structure, and the clinically relevant phenotypes associated with them, provides a new dimension for understanding T. vaginalis pathogenesis. In addition, our demonstration of the possibility of genetic exchange in the parasite has important implications for genetic research and control of the disease. Author Summary: The human parasite Trichomonas vaginalis causes trichomoniasis, the world's most common non-viral sexually transmitted infection. Research on T. vaginalis genetic diversity has been limited by a lack of appropriate genotyping tools. To address this problem, we recently published a panel of T. vaginalis-specific genetic markers; here we use these markers to genotype isolates collected from ten regions around the globe. We detect high levels of genetic diversity, infer a two-type population structure, identify clinically relevant differences between the two types, and uncover evidence of genetic exchange in what was believed to be a clonal organism. Together, these results greatly improve our understanding of the population genetics of T. vaginalis and provide insights into the possibility of genetic exchange in the parasite, with implications for the epidemiology and control of the disease. By taking into account the existence of different types and their unique characteristics, we can improve understanding of the wide range of symptoms that patients manifest and better implement appropriate drug treatment. In addition, by recognizing the possibility of genetic exchange, we are more equipped to address the growing concern of drug resistance and the mechanisms by which it may spread within parasite populations. [ABSTRACT FROM AUTHOR]

Blastocystis sp. is the most common eukaryotic parasite in the intestinal tract of humans. Due to its potential impact in public health, we determined the Blastocystis sp. subtypes (STs) and their relative frequency in symptomatic patients living in or in the vicinity of two Italian cities (Rome and Sassari). A total of 34 Blastocystis sp. isolates corresponding to 26 single and 4 mixed infections were subtyped using partial small subunit ribosomal RNA gene sequencing. From this molecular approach, the ST distribution in the present Italian population was as follows: ST3 (47.1%), ST2 (20.6%), ST4 (17.7%), ST1 (8.8%), and ST7, and ST8 (2.9%). As in almost all countries worldwide, ST3 was the most common ST reinforcing the hypothesis of its human origin. Together with a previous preliminary report, a total of seven STs (with the addition of ST5) have been found in Italian symptomatic patients. The wide range of STs identified in the Italian population suggest that Blastocystis sp. infection is not associated with specific STs even if some STs (ST1-ST4) are predominant as reported in all other countries. Since most of the STs identified in Italian patients are zoonotic, our data raise crucial questions concerning the identification of animal reservoirs for Blastocystis sp. and the potential risks of transmission to humans. [ABSTRACT FROM AUTHOR]

Giardia intestinalis is the microaerophilic protozoon causing giardiasis, a common infectious intestinal disease. Giardia possesses an O-scavenging activity likely essential for survival in the host. We report that Giardia trophozoites express the O-detoxifying flavodiiron protein (FDP), detected by immunoblotting, and are able to reduce O to HO rapidly (∼3 μM O × min × 10 cells at 37 °C) and with high affinity ( C = 3.4 ± 0.7 μM O). Following a short-term (minutes) exposure to HO ≥ 100 μM, the O consumption by the parasites is irreversibly impaired, and the FDP undergoes a degradation, prevented by the proteasome-inhibitor MG132. Instead, HO does not cause degradation or inactivation of the isolated FDP. On the basis of the elevated susceptibility of Giardia to oxidative stress, we hypothesize that the parasite preferentially colonizes the small intestine since, compared with colon, it is characterized by a greater capacity for redox buffering and a lower propensity to oxidative stress. © 2011 IUBMB IUBMB Life, 63(1): 21-25, 2011 [ABSTRACT FROM AUTHOR]

Background: Trichomonas vaginalis is the most common non-viral human sexually transmitted pathogen and importantly, contributes to facilitating the spread of HIV. Yet very little is known about its surface and secreted proteins mediating interactions with, and permitting the invasion and colonisation of, the host mucosa. Initial annotations of T. vaginalis genome identified a plethora of candidate extracellular proteins. Results: Data mining of the T. vaginalis genome identified 911 BspA-like entries (TvBspA) sharing TpLRR-like leucine-rich repeats, which represent the largest gene family encoding potential extracellular proteins for the pathogen. A broad range of microorganisms encoding BspA-like proteins was identified and these are mainly known to live on mucosal surfaces, among these T. vaginalis is endowed with the largest gene family. Over 190 TvBspA proteins with inferred transmembrane domains were characterised by a considerable structural diversity between their TpLRR and other types of repetitive sequences and two subfamilies possessed distinct classic sorting signal motifs for endocytosis. One TvBspA subfamily also shared a glycine-rich protein domain with proteins from Clostridium difficile pathogenic strains and C. difficile phages. Consistent with the hypothesis that TvBspA protein structural diversity implies diverse roles, we demonstrated for several TvBspA genes differential expression at the transcript level in different growth conditions. Identified variants of repetitive segments between several TvBspA paralogues and orthologues from two clinical isolates were also consistent with TpLRR and other repetitive sequences to be functionally important. For one TvBspA protein cell surface expression and antibody responses by both female and male T. vaginalis infected patients were also demonstrated. Conclusions: The biased mucosal habitat for microbial species encoding BspA-like proteins, the characterisation of a vast structural diversity for the TvBspA proteins, differential expression of a subset of TvBspA genes and the cellular localisation and immunological data for one TvBspA; all point to the importance of the TvBspA proteins to various aspects of T. vaginalis pathobiology at the host-pathogen interface. [ABSTRACT FROM AUTHOR]

Objectives: Persistence of antibodies against pathogens after antimicrobial treatment is a marker of therapy failure or evolution to a chronic infection. The kinetics of antibody production decrease following antigen elimination is highly variable, and predicting the duration of soluble immunity in infectious diseases is often impossible. This hampers the development and use of immunoassays for diagnostic and seroepidemiological purposes. In the case of Trichomonas vaginalis infection, the kinetics of antibody levels decrease following therapy has never been studied. We thus investigated the clearance of circulating anti-T. vaginalis IgGs after pharmacological treatment in patients affected by trichomoniasis.Methods: 18 female patients affected by acute trichomoniasis were enrolled in this study. After metronidazole therapy administration, subjects were followed up monthly up to 5 months, and serum levels of anti-T. vaginalis IgGs were measured by ELISA.Results: We showed that a successful therapy is characterised by a relatively fast decline of specific antibodies, until turning into negative by ELISA in 1-3 months. In a few patients we observed that the persistence of anti-T. vaginalis antibodies was associated with an evolution to chronic infection, which may be due to treatment failure or to reinfection by untreated sexual partners.Conclusions: Our results describe the direct correlation between the decline of a specific humoral anti-T. vaginalis response and an effective antimicrobial therapy. These findings may facilitate the follow-up approach to circumvent limitations in developing new diagnostic tools and techniques routinely used in microbiology laboratories to assess the presence of T. vaginalis in clinical samples. [ABSTRACT FROM AUTHOR]

Coronaviruses are known to be harmful and heterogeneous viruses, able to infect a large number of hosts. Among them, SADS-CoV (Swine Acute Diarrhea Syndrome Coronavirus), also known as PEAV (Porcine Enteric Alphacoronavirus), or SeA-CoV (Swine Enteric Alphacoronavirus), is the most recent Alphacoronavirus discovered, and caused several outbreaks reported in Chinese swine herds between late 2016 and 2019. We performed an upgraded phylodinamic reconstruction of SADS-CoV based on all whole genomes available on 21 June 2021. Results showed a very close relationship between SADS-CoV and HKU2-like CoV, which may represent the evolutionary intermediate step towards the present SADS-CoV. The direct progenitor of SADS-CoV is so far unknown and, although it is well known that horseshoe bats are reservoirs for Rhinolophus bat coronavirus HKU2-like (HKU2-like CoVs), the transmission path from bats to pigs is still unclear. The discrepancies in the phylogenetic position of rodent CoV, when different molecular markers were considered, corroborate the recombination hypothesis, suggesting that wild rats, which are frequent in farms, may have played a key role. The failure of the attempt at molecular dating, due to the lack of a clock signal, also corroborates the occurrence of a recombination event hypothesis. Zoonotic infections originating in wildlife can easily become a significant threat for human health. In such a context, due to the high recombination and cross-species capabilities of Coronavirus, SADS-CoV represents a possible high-risk pathogen for humans which needs a constant molecular monitoring. [ABSTRACT FROM AUTHOR]