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Molecules (Basel, Switzerland) Jun 2021A lichen is a symbiotic relationship between a fungus and a photosynthetic organism, which is algae or cyanobacteria. Endolichenic fungi are a group of microfungi that... (Review)
Review
A lichen is a symbiotic relationship between a fungus and a photosynthetic organism, which is algae or cyanobacteria. Endolichenic fungi are a group of microfungi that resides asymptomatically within the thalli of lichens. Endolichenic fungi can be recognized as luxuriant metabolic artists that produce propitious bioactive secondary metabolites. More than any other time, there is a worldwide search for new antibiotics due to the alarming increase in microbial resistance against the currently available therapeutics. Even though a few antimicrobial compounds have been isolated from endolichenic fungi, most of them have moderate activities, implying the need for further structural optimizations. Recognizing this timely need and the significance of endolichenic fungi as a promising source of antimicrobial compounds, the activity, sources and the structures of 31 antibacterial compounds, 58 antifungal compounds, two antiviral compounds and one antiplasmodial (antimalarial) compound are summarized in this review. In addition, an overview of the common scaffolds and structural features leading to the corresponding antimicrobial properties is provided as an aid for future studies. The current challenges and major drawbacks of research related to endolichenic fungi and the remedies for them have been suggested.
Topics: Anti-Infective Agents; Lichens
PubMed: 34202392
DOI: 10.3390/molecules26133901 -
Malaria Journal Sep 2021Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry...
BACKGROUND
Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission.
METHODS
In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa-Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals.
RESULTS
The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11-15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR.
CONCLUSIONS
This assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asymptomatic Infections; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Infant; Kenya; Malaria, Falciparum; Male; Middle Aged; Prevalence; Rural Population; Young Adult
PubMed: 34535134
DOI: 10.1186/s12936-021-03905-w -
Journal of Neuroinflammation Dec 2022HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available,...
BACKGROUND
HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit. Although HAM/TSP pathogenesis is not fully elucidated, older age, female sex and higher proviral load are established risk factors. We investigated systemic cytokines and a novel chronic inflammatory marker, GlycA, as possible biomarkers of immunopathogenesis and therapeutic response in HAM/TSP, and examined their interaction with established risk factors.
PATIENTS AND METHODS
We recruited 110 People living with HTLV-1 (PLHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients) with a total of 946 person-years of clinical follow-up. Plasma cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF) and GlycA were quantified by Cytometric Bead Array and NMR, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We used multivariable regression, machine learning algorithms and Bayesian network learning for biomarker identification.
RESULTS
We found that systemic IL-6 was positively correlated with both age (r = 0.50, p < 0.001) and GlycA (r = 0.45, p = 0.00049) in asymptomatics, revealing an 'inflammaging" signature which was absent in HAM/TSP. GlycA levels were higher in women (p = 0.0069), but cytokine levels did not differ between the sexes. IFN-γ (p = 0.007) and IL-17A (p = 0.0001) levels were increased in untreated HAM/TSP Multivariable logistic regression identified IL-17A and proviral load as independent determinants of clinical status, resulting in modest accuracy of predicting HAM/TSP status (64.1%), while a machine learning-derived decision tree classified HAM/TSP patients with 90.7% accuracy. Pre-treatment GlycA and TNF levels significantly predicted clinical worsening (measured by Osame Motor Disability Scale), independent of proviral load. In addition, a poor prednisolone response was significantly correlated with higher post-treatment IFN-γ levels. Likewise, a transcriptomic IFN signaling score, significantly correlated with previously proposed HAM/TSP biomarkers (CASP5/CXCL10/FCGR1A/STAT1), was efficiently blunted by in vitro prednisolone treatment of PBMC from PLHTLV-1 and incident HAM/TSP.
CONCLUSIONS
An age-related increase in systemic IL-6/GlycA levels reveals inflammaging in PLHTLV-1, in the absence of neurological disease. IFN-γ and IL-17A are biomarkers of untreated HAM/TSP, while pre-treatment GlycA and TNF predict therapeutic response to prednisolone pulse therapy, paving the way for a precision medicine approach in HAM/TSP.
Topics: Female; Humans; Bayes Theorem; Cytokines; Human T-lymphotropic virus 1; Interleukin-17; Interleukin-6; Leukocytes, Mononuclear; Motor Disorders; Neuroinflammatory Diseases; HTLV-I Infections
PubMed: 36482436
DOI: 10.1186/s12974-022-02658-w -
Virology Journal Dec 2019Zoonoses are infectious diseases transmitted directly or indirectly between animals and humans. Several important zoonotic pathogens colonize farm animals... (Review)
Review
Zoonoses are infectious diseases transmitted directly or indirectly between animals and humans. Several important zoonotic pathogens colonize farm animals asymptomatically, which may lead to contamination of the food chain and public health hazards. Moreover, routine sampling of carcasses at retail by government authorities over the past 20 years suggests the prevalence of antibiotic resistance in foodborne pathogens has increased. If this continues, antibiotics may be ineffective against such pathogens in the future and alternative approaches, such as phage therapy, may be necessary. Intensive livestock farming is the only realistic way of meeting the demand for meat from an increasing global population and growth in middle class consumers in developing countries, particularly in Asia. This review elaborates on the use of phages to control zoonotic pathogens in intensively-reared livestock (poultry and pigs).
Topics: Animals; Asia; Bacterial Infections; Carrier State; Food Contamination; Food Industry; Foodborne Diseases; Humans; Livestock; Phage Therapy; Veterinary Medicine
PubMed: 31831017
DOI: 10.1186/s12985-019-1260-3 -
Frontiers in Cellular and Infection... 2023(pneumococcus) typically colonizes the human upper airway asymptomatically but upon reaching other sites of the host body can cause an array of diseases such as... (Review)
Review
(pneumococcus) typically colonizes the human upper airway asymptomatically but upon reaching other sites of the host body can cause an array of diseases such as pneumonia, bacteremia, otitis media, and meningitis. Be it colonization or progression to disease state, pneumococcus faces multiple challenges posed by host immunity ranging from complement mediated killing to inflammation driven recruitment of bactericidal cells for the containment of the pathogen. Pneumococcus has evolved several mechanisms to evade the host inflicted immune attack. The major pneumococcal virulence factor, the polysaccharide capsule helps protect the bacteria from complement mediated opsonophagocytic killing. Another important group of pneumococcal proteins which help bacteria to establish and thrive in the host environment is surface associated glycosidases. These enzymes can hydrolyze host glycans on glycoproteins, glycolipids, and glycosaminoglycans and consequently help bacteria acquire carbohydrates for growth. Many of these glycosidases directly or indirectly facilitate bacterial adherence and are known to modulate the function of host defense/immune proteins likely by removing glycans and thereby affecting their stability and/or function. Furthermore, these enzymes are known to contribute the formation of biofilms, the bacterial communities inherently resilient to antimicrobials and host immune attack. In this review, we summarize the role of these enzymes in host immune evasion.
Topics: Humans; Streptococcus pneumoniae; Immune Evasion; Pneumococcal Infections; Glycoside Hydrolases; Polysaccharides; Bacterial Proteins
PubMed: 36816580
DOI: 10.3389/fcimb.2023.1109449 -
BMC Medicine Nov 2022Asymptomatic COVID-19 cases have complicated the surveillance and tracking of the pandemic. Previous studies have estimated that 15-25% of all infectees remain...
BACKGROUND
Asymptomatic COVID-19 cases have complicated the surveillance and tracking of the pandemic. Previous studies have estimated that 15-25% of all infectees remain asymptomatic.
METHODS
Based on contact tracing data from Oslo, Norway, we estimated transmission and susceptibility dynamics among symptomatic and asymptomatic cases and their contacts as identified by manual contact tracing between September 1, 2020, and September 1, 2021.
RESULTS
Among 27,473 indexes and 164,153 registered contacts, the secondary attack rate (SAR-14) was estimated to be 28% lower through asymptomatic exposure (13%) compared to symptomatic exposure (18%). Furthermore, those infected by asymptomatic cases were almost three times more likely to be asymptomatic compared to those infected by symptomatic cases.
CONCLUSIONS
Symptomatic cases spread the virus to a greater extent than asymptomatic, and infectees are more likely to be asymptomatic if their assumed infector was asymptomatic.
Topics: Humans; SARS-CoV-2; Contact Tracing; COVID-19; Pandemics; Norway
PubMed: 36348327
DOI: 10.1186/s12916-022-02642-4 -
Antimicrobial Resistance and Infection... Sep 2023As today's most prevalent and costly healthcare-associated infection, hospital-onset Clostridioides difficile infection (HO-CDI) represents a major threat to patient... (Review)
Review
As today's most prevalent and costly healthcare-associated infection, hospital-onset Clostridioides difficile infection (HO-CDI) represents a major threat to patient safety world-wide. This review will discuss how new insights into the epidemiology of CDI have quantified the prevalence of C. difficile (CD) spore contamination of the patient-zone as well as the role of asymptomatically colonized patients who unavoidable contaminate their near and distant environments with resilient spores. Clarification of the epidemiology of CD in parallel with the development of a new generation of sporicidal agents which can be used on a daily basis without damaging surfaces, equipment, or the environment, led to the research discussed in this review. These advances underscore the potential for significantly mitigating HO-CDI when combined with ongoing programs for optimizing the thoroughness of cleaning as well as disinfection. The consequence of this paradigm-shift in environmental hygiene practice, particularly when combined with advances in hand hygiene practice, has the potential for significantly improving patient safety in hospitals globally by mitigating the acquisition of CD spores and, quite plausibly, other environmentally transmitted healthcare-associated pathogens.
Topics: Humans; Clostridioides difficile; Health Facilities; Hospitals; Patient Safety; Clostridium Infections
PubMed: 37679758
DOI: 10.1186/s13756-023-01295-z -
Antimicrobial Agents and Chemotherapy Aug 2022Malaria control relies on passive case detection, and this strategy fails detecting asymptomatic infections. In addition, infections in endemic areas harbor multiple...
Malaria control relies on passive case detection, and this strategy fails detecting asymptomatic infections. In addition, infections in endemic areas harbor multiple parasite genotypes that could affect case management and malaria epidemiology. Here, we performed AmpSeq genotyping to capture polymorphisms associated with antimalarial resistance and the genetic diversity within natural Plasmodium falciparum infections. Known genetic polymorphisms associated with altered drug susceptibility were screened for the five most common marker genes, , , , , and , and genetic diversity was established from two known AmpSeq markers, and . Relative abundance of the different genotypes within mixed infections was calculated from the number of reads per genotype. Genotyping was performed on 117 samples, 63 from asymptomatic and 54 from symptomatic individuals. We identified up to 15 genotypes within an infection, and the median multiplicity of infection was higher in asymptomatic infections (median MOI = 5 in asymptomatics versus median MOI = 2 in symptomatics, 0.001). No genetic differentiation on parasites from asymptomatic and symptomatic individuals was found. No mutation associated with ART resistance was identified. Prevalence of the P. falciparum chloroquine resistance wild-type genotype (CVMNK) reached 80%, confirming a return to chloroquine (CQ) sensitive parasites in Cameroon. In addition, the CQ-associated resistant genotype (CVIET) was present at very low density in polyclonal infections. Persistence of low-density chloroquine resistant parasites indicates competition-survival trade-offs may contribute to maintaining genetic diversity . Thus, monitoring the expansion of these low-density genotypes in different immune backgrounds will be critical to evaluate drug policy changes.
Topics: Antimalarials; Asymptomatic Infections; Chloroquine; Drug Resistance; Folic Acid Antagonists; Genotype; Humans; Malaria; Malaria, Falciparum; Mutation; Plasmodium falciparum; Protozoan Proteins
PubMed: 35862750
DOI: 10.1128/aac.00188-22 -
Frontiers in Immunology 2021Successful pathogens require metabolic flexibility to adapt to diverse host niches. The presence of co-infecting or commensal microorganisms at a given infection site... (Review)
Review
Successful pathogens require metabolic flexibility to adapt to diverse host niches. The presence of co-infecting or commensal microorganisms at a given infection site can further influence the metabolic processes required for a pathogen to cause disease. The Gram-positive bacterium and the polymorphic fungus are microorganisms that asymptomatically colonize healthy individuals but can also cause superficial infections or severe invasive disease. Due to many shared host niches, and are frequently co-isolated from mixed fungal-bacterial infections. and co-infection alters microbial metabolism relative to infection with either organism alone. Metabolic changes during co-infection regulate virulence, such as enhancing toxin production in or contributing to morphogenesis and cell wall remodeling in . and also form polymicrobial biofilms, which have greater biomass and reduced susceptibility to antimicrobials relative to mono-microbial biofilms. The and metabolic programs induced during co-infection impact interactions with host immune cells, resulting in greater microbial survival and immune evasion. Conversely, innate immune cell sensing of and triggers metabolic changes in the host cells that result in an altered immune response to secondary infections. In this review article, we discuss the metabolic programs that govern host-pathogen interactions during and co-infection. Understanding interactions may highlight more general principles of how polymicrobial interactions, particularly fungal-bacterial interactions, shape the outcome of infectious disease. We focus on how co-infection alters microbial metabolism to enhance virulence and how infection-induced changes to host cell metabolism can impact a secondary infection.
Topics: Adaptation, Physiological; Animals; Biofilms; Candida albicans; Candidiasis; Coinfection; Humans; Microbial Interactions; Staphylococcal Infections; Staphylococcus aureus
PubMed: 34956233
DOI: 10.3389/fimmu.2021.797550 -
Cellular Microbiology Nov 2019Neisseria meningitidis is a Gram-negative bacterium that asymptomatically colonises the nasopharynx of humans. For an unknown reason, N. meningitidis can cross the... (Review)
Review
Neisseria meningitidis is a Gram-negative bacterium that asymptomatically colonises the nasopharynx of humans. For an unknown reason, N. meningitidis can cross the nasopharyngeal barrier and invade the bloodstream where it becomes one of the most harmful extracellular bacterial pathogen. This infectious cycle involves the colonisation of two different environments. (a) In the nasopharynx, N. meningitidis grow on the top of mucus-producing epithelial cells surrounded by a complex microbiota. To survive and grow in this challenging environment, the meningococcus expresses specific virulence factors such as polymorphic toxins and MDAΦ. (b) Meningococci have the ability to survive in the extra cellular fluids including blood and cerebrospinal fluid. The interaction of N. meningitidis with human endothelial cells leads to the formation of typical microcolonies that extend overtime and promote vascular injury, disseminated intravascular coagulation, and acute inflammation. In this review, we will focus on the interplay between N. meningitidis and these two different niches at the cellular and molecular level and discuss the use of inhibitors of piliation as a potent therapeutic approach.
Topics: Bacterial Toxins; Blood Vessels; Endothelial Cells; Epithelial Cells; Host Microbial Interactions; Humans; Inovirus; Meningococcal Infections; Nasopharynx; Neisseria meningitidis; Virulence Factors
PubMed: 31167044
DOI: 10.1111/cmi.13063