Frontiers in Cellular and Infection Microbiology
Latest Publications





Published By Frontiers Media Sa

Updated Tuesday, 23 November 2021

Md. Taibur Rahman ◽  
Izabela J. Swierzy ◽  
Bryan Downie ◽  
Gabriela Salinas ◽  
Martin Blume ◽  

Toxoplasma gondii is an obligatory intracellular parasite that causes persistent infections in birds and mammals including ~30% of the world’s human population. Differentiation from proliferative and metabolically active tachyzoites to largely dormant bradyzoites initiates the chronic phase of infection and occurs predominantly in brain and muscle tissues. Here we used murine skeletal muscle cells (SkMCs) to decipher host cellular factors that favor T. gondii bradyzoite formation in terminally differentiated and syncytial myotubes, but not in proliferating myoblast precursors. Genome-wide transcriptome analyses of T. gondii-infected SkMCs and non-infected controls identified ~6,500 genes which were differentially expressed (DEGs) in myotubes compared to myoblasts, largely irrespective of infection. On the other hand, genes related to central carbohydrate metabolism, to redox homeostasis, and to the Nrf2-dependent stress response pathway were enriched in both infected myoblast precursors and myotubes. Stable isotope-resolved metabolite profiling indicated increased fluxes into the oxidative branch of the pentose phosphate pathway (OxPPP) in infected myoblasts and into the TCA cycle in infected myotubes. High OxPPP activity in infected myoblasts was associated with increased NADPH/NADP+ ratio while myotubes exhibited higher ROS levels and lower expression of anti-oxidants and detoxification enzymes. Pharmacological reduction of ROS levels in SkMCs inhibited bradyzoite differentiation, while increased ROS induced bradyzoite formation. Thus, we identified a novel host cell-dependent mechanism that triggers stage conversion of T. gondii into persistent tissue cysts in its natural host cell type.

Rahel L. Birru ◽  
Kiflai Bein ◽  
Natalya Bondarchuk ◽  
Heather Wells ◽  
Qiao Lin ◽  

Bacterial infections contribute to accelerated progression and severity of chronic obstructive pulmonary disease (COPD). Apples have been associated with reduced symptoms of COPD and disease development due to their polyphenolic content. We examined if phloretin, an apple polyphenol, could inhibit bacterial growth and inflammation induced by the main pathogens associated with COPD. Phloretin displayed bacteriostatic and anti-biofilm activity against nontypeable Haemophilus influenzae (NTHi), Moraxella catarrhalis, Streptococcus pneumoniae, and to a lesser extent, Pseudomonas aeruginosa. In vitro, phloretin inhibited NTHi adherence to NCI-H292 cells, a respiratory epithelial cell line. Phloretin also exhibited anti-inflammatory activity in COPD pathogen-induced RAW 264.7 macrophages and human bronchial epithelial cells derived from normal and COPD diseased lungs. In mice, NTHi bacterial load and chemokine (C-X-C motif) ligand 1 (CXCL1), a neutrophil chemoattractant, was attenuated by a diet supplemented with phloretin. Our data suggests that phloretin is a promising antimicrobial and anti-inflammatory nutraceutical for reducing bacterial-induced injury in COPD.

Ayorinde O. Afolayan ◽  
Elena Biagi ◽  
Simone Rampelli ◽  
Marco Candela ◽  
Patrizia Brigidi ◽  

Despite well-established knowledge of the role of diet and the geographic effect on the gut microbiota of human populations, the temporal dynamics of the individual microbiota profile across changes associated with intercontinental short residence are still far from being understood. This pilot study sought to provide insights into the trajectory of the gut microbiota of an individual during a two-month stay in Italy and a subsequent two-month stay in Nigeria, by 16S rRNA gene sequencing and inferred metagenomics. The gut microbiota underwent massive but temporary changes, both taxonomically and based on predicted functionality. The faecal microbiota associated with the short stay in Italy progressively lost diversity and showed a dominance of Firmicutes, while after returning to Nigeria, the microbial community quickly regained the typical profile, in terms of biodiversity and bacterial signatures of traditional lifestyle, i.e., Prevotella and Treponema. Predicted pathways involved in glycolysis, fermentation and N-acetylneuraminate degradation were enriched during the subsequent two-month stay in Nigeria, whereas pathways associated with amino acid and peptidoglycan synthesis and maturation became over-represented during short stay in Italy. Our findings stress the plasticity of the individual gut microbiota even during a short-term travel, with loss/gain of taxonomic and functional features that mirror those of the gut microbiota of indigenous people dwelling therein.

Jose Antonio Reales-Calderon ◽  
Gloria H. W. Tso ◽  
Alrina S. M. Tan ◽  
Pei Xiang Hor ◽  
Julia Böhme ◽  

Serial passaging of the human fungal pathogen Candida albicans in the gastrointestinal tract of antibiotics-treated mice selects for virulence-attenuated strains. These gut-evolved strains protect the host from infection by a wide range of pathogens via trained immunity. Here, we further investigated the molecular and cellular mechanisms underlying this innate immune memory. Both Dectin-1 (the main receptor for β-glucan; a well-described immune training molecule in the fungal cell wall) and Nod2 (a receptor described to mediate BCG-induced trained immunity), were redundant for the protection induced by gut-evolved C. albicans against a virulent C. albicans strain, suggesting that gut-evolved C. albicans strains induce trained immunity via other pathways. Cytometry by time of flight (CyTOF) analysis of mouse splenocytes revealed that immunization with gut-evolved C. albicans resulted in an expansion of neutrophils and a reduction in natural killer (NK) cells, but no significant numeric changes in monocytes, macrophages or dendritic cell populations. Systemic depletion of phagocytes or neutrophils, but not of macrophages or NK cells, reduced protection mediated by gut-evolved C. albicans. Splenocytes and bone marrow cells of mice immunized with gut-evolved C. albicans demonstrated metabolic changes. In particular, splenic neutrophils displayed significantly elevated glycolytic and respiratory activity in comparison to those from mock-immunized mice. Although further investigation is required for fully deciphering the trained immunity mechanism induced by gut-evolved C. albicans strains, this data is consistent with the existence of several mechanisms of trained immunity, triggered by different training stimuli and involving different immune molecules and cell types.

Junyan Qu ◽  
Xijiao Liu ◽  
Xiaoju Lv

The aim was to better understand the clinical characteristics of patients with mucormycosis in western China. We retrospectively investigated the clinical, laboratory, radiological and treatment profiles of mucormycosis patients during a 10-year period (2010–2019). As a result, 59 proven mucormycosis were enrolled in this study. It was found that 52.5% of patients had worse clinical outcomes. Pulmonary mucormycosis (PM) was the most common clinical manifestation. The most frequent risk factor was diabetes mellitus (38, 64.4%) for mucormycosis patients. Cough (43, 93.5%), fever (24, 52.2%) and hemoptysis/bloody phlegm (21, 45.7%) were the most common manifestations of PM. There were no differences in clinical manifestations, risk factors and laboratory tests between different clinical outcome groups (P>0.05). Lymph node enlargement (30, 65.2%), patchy shadows (28, 60.9%), cavitation (25, 53.3%) and bilateral lobe involvement (39, 84.8%) were the most common on chest CT. Nodule was more common in good outcome group (P <0.05). A total of 48 cases (81.4%) were confirmed by histopathological examination, 22 cases (37.3%) were confirmed by direct microscopy. PM patients were treated with amphotericin B/amphotericin B liposome or posaconazale had better clinical outcomes (P <0.05). In conclusion, PM was the most common clinical type of mucormycosis in China. Diabetes mellitus was the most common risk factor. PM has diverse imaging manifestations and was prone to bilateral lobes involvement. Early diagnosis and effective anti-mucor treatment contribute to successful treatment.

Nengneng Zheng ◽  
Renyong Guo ◽  
Jinxi Wang ◽  
Wei Zhou ◽  
Zongxin Ling

Lactobacillus iners, first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As L. iners does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically on blood agar, it has been initially overlooked by traditional culture methods. It was not until the wide application of molecular biology techniques that the function of L. iners in the vaginal microbiome was carefully explored. L. iners has the smallest genome among known Lactobacilli and it has many probiotic characteristics, but is partly different from other major vaginal Lactobacillus species, such as L. crispatus, in contributing to the maintenance of a healthy vaginal microbiome. It is not only commonly present in the healthy vagina but quite often recovered in high numbers in bacterial vaginosis (BV). Increasing evidence suggests that L. iners is a transitional species that colonizes after the vaginal environment is disturbed and offers overall less protection against vaginal dysbiosis and, subsequently, leads to BV, sexually transmitted infections, and adverse pregnancy outcomes. Accordingly, under certain conditions, L. iners is a genuine vaginal symbiont, but it also seems to be an opportunistic pathogen. Further studies are necessary to identify the exact role of this intriguing species in vaginal health and diseases.

Caixian Zhou ◽  
Yao Zhang ◽  
Simin Wu ◽  
Zhiheng Wang ◽  
Waresi Tuersong ◽  

CircRNAs, a novel class of ncRNA family, are endogenous transcriptional products involved in various biological and physiological processes in plants and animals. However, almost no information is available for circRNAs of parasitic helminths. In the present study, the circRNAs repertoire was comprehensively explored in Haemonchus contortus, a blood-sucking parasitic nematode of ruminants. In total, 20073 circRNAs were identified and annotated from three key developmental stages/genders of H. contortus including the free-living infective third-stage larvae (L3, 18883), parasitic adult female (Af, 3491), and male worms (Am, 2550) via deep-sequencing technology and bioinformatic analysis. Among these identified circRNAs, 71% were derived from exonic regions of protein-coding genes. The number of circRNAs transcribed from the X chromosome (4704) was higher than that from Chromosome I-V (3143, 3273, 3041, 3030, 2882). The amount of highly expressed circRNAs in third-stage larvae was significantly more abundant than that in adult stage. 15948 and 16847 circRNAs were differentially expressed between Af and L3s and between Am and L3, respectively. Among them, 13409 circRNAs existed in both comparisons. Furthermore, 1119 circRNAs were differentially expressed between Af_and_Am. GO enrichment analysis indicated that source genes of circRNAs differentially expressed between Am and L3 as well as between Af and L3 were significantly enriched in many biological processes, primarily including signaling, signal transduction and cell communication terms. KEGG analysis revealed that parental genes of differentially expressed circRNAs were mainly related to metabolism (pyruvate metabolism, glycerophospholipid metabolism, and carbon metabolism), MAPK signaling pathway, and phosphatidylinositol signaling system. Moreover, many circRNAs contained one or more miRNA potential binding sites, suggesting that they could regulate gene expression at the post-transcriptional level. Furthermore, the correctness of head-to-tail back splicing site and alternative circularization events were verified by Sanger sequencing using both divergent and convergent primers. Finally, the reliability of RNA-Seq data and the resistance of circRNAs to RNase R digestion were confirmed by quantitative RT-PCR. Taken together, our findings provide a foundation for elucidating the regulatory mechanisms of circRNAs in H. contortus, which will advance the understanding of circRNAs in parasitic nematodes.

Na Yao ◽  
Qiong Xu ◽  
Jia-Kang He ◽  
Ming Pan ◽  
Zhao-Feng Hou ◽  

Toxoplasma gondii is a serious hazard to public health and animal husbandry. Due to the current dilemma of treatment of toxoplasmosis, it is urgent to find new anti-T. gondii drugs to treat toxoplasmosis. In this study, the anti-T. gondii activity of Origanum vulgare essential oil (Ov EO) was firstly studied, and then, carvanol (Ca), the main ingredient of Ov EO was evaluated using the MTT assay on human foreskin fibroblast (HFF) cells in vitro. The cytotoxicity was evaluated using the MTT assay on HFF cells. The CC50 of Ov EO and Ca was 134.9 and 43.93 μg/ml, respectively. Both of them exhibited anti-parasitic activity, and inhibited the growth of T. gondii in a dose-dependent manner. For the inhibition effect, Ca was better than Ov EO at the same concentration, the IC50 of Ov EO and Ca was 16.08 and 7.688 μg/ml, respectively. In addition, treatment with Ca, was found to change the morphology of T. gondii tachyzoites and made their shapes curl up. These results showed that Ca was able to inhibit the proliferation of T. gondii by reducing invasion, which may be due to its detrimental effect on the mobility of tachyzoites. Our results indicated that Ca could be a potential new and effective drug for treating toxoplasmosis.

Mayumi Ueta ◽  
Koji Hosomi ◽  
Jonguk Park ◽  
Kenji Mizuguchi ◽  
Chie Sotozono ◽  

The commensal microbiota is involved in a variety of diseases. Our group has noticed that patients with Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) often present with persistent inflammation of the ocular surface, even in the chronic stage, and that this inflammation is exacerbated by colonization of the mucosa by certain bacteria. However, the changes in the composition of the ocular microbiome in SJS/TEN patients with severe ocular complications (SOCs) remain to be fully investigated. Here, we conducted a cross-sectional study of 46 Japanese subjects comprising 9 healthy control subjects and 37 SJS/TEN patients with SOC. The 16S rRNA-based genetic analyses revealed that the diversity of the ocular microbiome was reduced in SJS/TEN patients with SOC compared with that in healthy control subjects. Principal coordinate analysis based on Bray–Curtis distance at the genus level revealed that the relative composition of the ocular microbiome was different in healthy control subjects and SJS/TEN patients with SOC, and that the SJS/TEN patients with SOC could be divided into four groups based on whether their microbiome was characterized by enrichment of species in genus Corynebacterium 1, Neisseriaceae uncultured, or Staphylococcus or by simultaneous enrichment in species in genera Propionibacterium, Streptococcus, Fusobacterium, Lawsonella, and Serratia. Collectively, our findings indicate that enrichment of certain bacteria at the ocular surface could be associated with ocular surface inflammation in SJS/TEN patients with SOC.

Nan Shen ◽  
Yuanjie Zhou ◽  
Yajuan Zhou ◽  
Lijuan Luo ◽  
Wenjuan Chen ◽  

ObjectivesOveruse of antibiotics and antibiotic resistance are global healthcare problems. In pediatric patients with respiratory infections, viral and bacterial etiologies are challenging to distinguish, leading to irrational antibiotic use. Rapid and accurate molecular diagnostic testing methods for respiratory pathogens has been shown to facilitate effective clinical decision-making and guide antibiotic stewardship interventions in the developed regions, but its impacts on pediatric patient care in the developing countries remain unclear.MethodsIn this single-center, retrospective case-control study, we compared demographics, clinical characteristics, especially microbiological findings, and antibiotic usage between pediatric patients with respiratory infection receiving FilmArray Respiratory Panel (FilmArray RP) testing and a matched routine testing control group. Our primary outcome was the duration of intravenous antibiotics treatment (DOT) during hospitalization.ResultsEach group consisted of 346 children with a respiratory infection. In the FilmArray RP testing group, the DOT was shorter than that in the routine testing group (6.41 ± 3.67 days versus 7.23 ± 4.27 days; p = 0.006). More patients in the FilmArray RP testing group de-escalated antibiotic treatments within 72 hours of hospitalization (7.80%, 27/346 versus 2.60%, 9/346; p = 0.002). By contrast, fewer patients in the FilmArray RP testing group had escalated antibiotic treatments between 72 hours and seven days (7.80% versus 14.16%; p = 0.007). The cost of hospitalization was significantly lower in the FilmArray RP testing group ($ 1413.51 ± 1438.01 versus $ 1759.37 ± 1929.22; p = 0.008). Notably, the subgroup analyses revealed that the FilmArray RP test could shorten the DOT, improve early de-escalation of intravenous antibiotics within 72 hours of hospitalization, decline the escalation of intravenous antibiotics between 72 hours and seven days, and reduce the cost of hospitalization for both patient populations with or without underlying diseases.ConclusionsMolecular point-of-care testing for respiratory pathogens could help to reduce intravenous antibiotic use and health care costs of pediatric patients with respiratory infections in developing countries.

Sign in / Sign up

Export Citation Format

Share Document