RESUMEN
BACKGROUND: The oral cavity represents a main entrance of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE-2), neuropilin-1 (NRP-1), and transmembrane serine protease 2 (TMPRSS2) are essential for the entry of SARS-CoV-2 to the host cells. Both ACE-2 and NRP-1 receptors and TMPRSS2 have been identified in the oral cavity. However, there is limited knowledge about the impact of periapical lesions and their metabolites on the expression of these critical genes. This study aims to measure the impact of periapical lesions and their unique fatty acids (FAs) metabolites on the expression of the aforementioned genes, in addition to interleukin 6 (IL-6) gene and hence SARS-CoV-2 infection loads can be estimated. METHODS: Gene expression of ACE-2, NRP-1, TMPRSS2, and IL-6 was performed in periapical lesions in comparison to healthy oral cavity. Since FAs are important immunomodulators required for the lipid synthesis essential for receptors synthesis and viral replication, comparative FAs profiling was determined in oral lesions and healthy pulp tissues using gas chromatography-mass spectrometry (GC-MS). The effect of major identified and unique FAs was tested on mammalian cells known to express ACE-2, NRP-1, and TMPRSS2 genes. RESULTS: Gene expression analysis indicated that ACE-2, NRP-1, and TMPRSS2 were significantly upregulated in healthy clinical samples compared to oral lesions, while the reverse was true with IL-6 gene expression. Saturated and monounsaturated FAs were the major identified shared and unique FAs, respectively. Major shared FAs included palmitic, stearic and myristic acids with the highest percentage in the healthy oral cavity, while unique FAs included 17-octadecynoic acid in periapical abscess, petroselinic acid and L-lactic acid in periapical granuloma, and 1-nonadecene in the radicular cyst. Computational prediction showed that the binding affinity of identified FAs to ACE-2, TMPRSS2 and S protein were insignificant. Further, FA-treated mammalian cells showed significant overexpression of ACE-2, NRP-1 and TMPRSS2 genes except with L-lactic acid and oleic acid caused downregulation of NRP-1 gene, while 17-octadecynoic acid caused insignificant effect. CONCLUSION: Collectively, a healthy oral cavity is more susceptible to viral infection when compared to that complicated with periapical lesions. FAs play important role in viral infection and their balance can affect the viral loads. Shifting the balance towards higher levels of palmitic, stearic and 1-nonadecene caused significant upregulation of the aforementioned genes and hence higher viral loads. On the other hand, there is a reverse correlation between inflammation and expression of SARS-CoV-2 receptors. Therefore, a mouth preparation that can reduce the levels of palmitic, stearic and 1-nonadecene, while maintaining an immunomodulatory effect can be employed as a future protection strategy against viral infection.
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COVID-19 , SARS-CoV-2 , Animales , Humanos , Boca , Carga ViralRESUMEN
The population dynamics of human to mosquito malaria transmission in the field has important implications for the genetics, epidemiology and control of malaria. The number of oocysts in oocyst-positive mosquitoes developing from a single, naturally acquired infectious blood meal (herein referred to as a single-feed infection load) greatly influences the efficacy of transmission blocking interventions but still remains poorly documented. During a year-long analysis of malaria parasite transmission in Burkina Faso we caught and dissected wild malaria vectors to assess Plasmodium oocyst prevalence and load (the number of oocysts counted in mosquitoes with detectable oocysts) and the prevalence of salivary gland sporozoites. This was compared with malaria endemicity in the human population, assessed in cross-sectional surveys. Data were analysed using a novel transmission mathematical model to estimate the per bite transmission probability and the average single-feed infection load for each location. The observed oocyst load and the estimated single-feed infection load in naturally infected mosquitoes were substantially higher than previous estimates (means ranging from 3.2 to 24.5 according to seasons and locations) and indicate a strong positive association between the single-feed infection load and parasite prevalence in humans. This work suggests that highly infected mosquitoes are not rare in the field and might have a greater influence on the epidemiology and genetics of the parasite, and on the efficacy of novel transmission blocking interventions.
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Anopheles , Malaria , Oocistos/aislamiento & purificación , Plasmodium falciparum/aislamiento & purificación , Animales , Anopheles/parasitología , Burkina Faso , Estudios Transversales , Humanos , Malaria/transmisión , Mosquitos Vectores/parasitologíaRESUMEN
Modelling evolution of virulence in host-parasite systems is an actively developing area of research with ever-growing literature. However, most of the existing studies overlook the fact that individuals within an infected population may have a variable infection load, i.e. infected populations are naturally structured with respect to the parasite burden. Empirical data suggests that the mortality and infectiousness of individuals can strongly depend on their infection load; moreover, the shape of distribution of infection load may vary on ecological and evolutionary time scales. Here we show that distributed infection load may have important consequences for the eventual evolution of virulence as compared to a similar model without structuring. Mathematically, we consider an SI model, where the dynamics of the infected subpopulation is described by a von Förster-type equation, in which the infection load plays the role of age. We implement the adaptive dynamics framework to predict evolutionary outcomes in this model. We demonstrate that for simple trade-off functions between virulence, disease transmission and parasite growth rates, multiple evolutionary attractors are possible. Interestingly, unlike in the case of unstructured models, achieving an evolutionary stable strategy becomes possible even for a variation of a single ecological parameter (the parasite growth rate) and keeping the other parameters constant. We conclude that evolution in disease-structured populations is strongly mediated by alterations in the overall shape of the parasite load distribution.
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Evolución Molecular , Modelos Biológicos , Parásitos/patogenicidad , Infecciones por Protozoos/parasitología , Virulencia/genética , Animales , Interacciones Huésped-Parásitos/genética , Humanos , Carga de Parásitos , Parásitos/genética , Infecciones por Protozoos/transmisiónRESUMEN
Mycoplasma genitalium is a common sexually transmitted infection with a propensity to acquire resistance to commonly used antimicrobial therapies. Bacterial load has been linked to patient symptoms and the success of treatment. In this study, we demonstrate methodology to estimate load from routine diagnostic assays using the ResistancePlus MG test (SpeeDx Pty Ltd., Australia). The method gave comparable quantitation to an M. genitalium-specific 16S rRNA quantitative PCR (qPCR; Spearman r = 0.94) for the samples analyzed (n = 499, including urine and swab types as detailed below) and was, therefore, employed to analyze typical load levels for samples in a diagnostic laboratory (total of 1,012 tests). When stratified by sample type, female urine (median, 826 genomes/ml) had the lowest load. This was significantly lower than median loads for all other sample types (male urine [6.91 × 103 genomes/ml], anal swabs [5.50 × 103], cervical swabs [8.15 × 103], endocervical swabs [3.97 × 103], and vaginal swabs [6.95 × 103]) (P < 0.0001). There were no significant differences in load estimates between the other sample types. Reproducibility of load estimates conducted on the same samples was high (r > 0.85). In conclusion, this methodology to provide load estimates for M. genitalium can be easily integrated into routine diagnostic laboratory workflow. Given the association between organism load, symptoms, and treatment success, load assessment has future diagnostic potential.
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Carga Bacteriana/métodos , Infecciones por Mycoplasma/microbiología , Mycoplasma genitalium/aislamiento & purificación , Australia , ADN Bacteriano/genética , Femenino , Humanos , Masculino , ARN Ribosómico 16S/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los ResultadosRESUMEN
Background & objectives: : Immune complexes (ICs) play a crucial role which can either be beneficial or pathological to the host. Involvement of circulating immune complexes (CICs) has been shown in tuberculosis (TB) cases (adults and neonates form), but its immunomodulatory effect has not been studied in vivo. Hence, this study was carried out to understand and explore the prognostic therapeutic potential of CICs on the host immune system in guinea pigs animal TB model. Methods: In this study, the guinea pigs (group I) were immunized with in vitro synthesized antigen excess IC (AgX-IC), group II with antibody excess IC (AbX-IC) and group III with phosphate-buffered saline. All these animals were sensitized with Mycobacterium tuberculosis H37Rv before immunization and subsequently infected with M. tuberculosis H37Rv strain post-immunization with IC. Results: Mortality was observed in animals belonging of groups II and III, while all animals in group I survived. A steady increase in the body weight of animals immunized with AgX-IC was observed when compared to the other groups. The infection load in the spleen and lungs was less in animals from group I when compared to the other groups. The CICs were found to be in higher concentration in serum of IC-immunized guinea pigs when compared to ICs non-immunized animals. Interpretation & conclusions: Based on our findings, it can be speculated that the ICs may have a protective immunomodulatory role pertaining to disease progression and development of pathology. As a new perspective, with further insight into the underlying mechanism of action and correlation with clinical data, ICs may also be used as a potential tool for assessing the immune status of the infected individuals, especially the close contacts of TB patients.