scholarly journals Molecular Hydrogen Metabolism: a Widespread Trait of Pathogenic Bacteria and Protists

2020 ◽  
Vol 84 (1) ◽  
Author(s):  
Stéphane L. Benoit ◽  
Robert J. Maier ◽  
R. Gary Sawers ◽  
Chris Greening
Keyword(s):  
Molecular Hydrogen ◽  
Trichomonas Vaginalis ◽  
Pathogenic Bacteria ◽  
Anaerobic Bacteria ◽  
Anaerobic Respiration ◽  
Hydrogen Metabolism ◽  
Human Pathogens ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Holistic Understanding

SUMMARY Pathogenic microorganisms use various mechanisms to conserve energy in host tissues and environmental reservoirs. One widespread but often overlooked means of energy conservation is through the consumption or production of molecular hydrogen (H2). Here, we comprehensively review the distribution, biochemistry, and physiology of H2 metabolism in pathogens. Over 200 pathogens and pathobionts carry genes for hydrogenases, the enzymes responsible for H2 oxidation and/or production. Furthermore, at least 46 of these species have been experimentally shown to consume or produce H2. Several major human pathogens use the large amounts of H2 produced by colonic microbiota as an energy source for aerobic or anaerobic respiration. This process has been shown to be critical for growth and virulence of the gastrointestinal bacteria Salmonella enterica serovar Typhimurium, Campylobacter jejuni, Campylobacter concisus, and Helicobacter pylori (including carcinogenic strains). H2 oxidation is generally a facultative trait controlled by central regulators in response to energy and oxidant availability. Other bacterial and protist pathogens produce H2 as a diffusible end product of fermentation processes. These include facultative anaerobes such as Escherichia coli, S. Typhimurium, and Giardia intestinalis, which persist by fermentation when limited for respiratory electron acceptors, as well as obligate anaerobes, such as Clostridium perfringens, Clostridioides difficile, and Trichomonas vaginalis, that produce large amounts of H2 during growth. Overall, there is a rich literature on hydrogenases in growth, survival, and virulence in some pathogens. However, we lack a detailed understanding of H2 metabolism in most pathogens, especially obligately anaerobic bacteria, as well as a holistic understanding of gastrointestinal H2 transactions overall. Based on these findings, we also evaluate H2 metabolism as a possible target for drug development or other therapies.

scholarly journals How the Anaerobic Enteropathogen Clostridioides difficile Tolerates Low O2 Tensions

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Nicolas Kint ◽  
Carolina Alves Feliciano ◽  
Maria C. Martins ◽  
Claire Morvan ◽  
Susana F. Fernandes ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Anaerobic Bacteria ◽  
Growth Defect ◽  
Strictly Anaerobic ◽  
Low Oxygen ◽  
Air Exposure ◽  
Vegetative Cells ◽  
Content Type ◽  
Clostridioides Difficile

ABSTRACT Clostridioides difficile is a major cause of diarrhea associated with antibiotherapy. After germination of C. difficile spores in the small intestine, vegetative cells are exposed to low oxygen (O2) tensions. While considered strictly anaerobic, C. difficile is able to grow in nonstrict anaerobic conditions (1 to 3% O2) and tolerates brief air exposure indicating that this bacterium harbors an arsenal of proteins involved in O2 detoxification and/or protection. Tolerance of C. difficile to low O2 tensions requires the presence of the alternative sigma factor, σB, involved in the general stress response. Among the genes positively controlled by σB, four encode proteins likely involved in O2 detoxification: two flavodiiron proteins (FdpA and FdpF) and two reverse rubrerythrins (revRbr1 and revRbr2). As previously observed for FdpF, we showed that both purified revRbr1 and revRbr2 harbor NADH-linked O2- and H2O2-reductase activities in vitro, while purified FdpA mainly acts as an O2-reductase. The growth of a fdpA mutant is affected at 0.4% O2, while inactivation of both revRbrs leads to a growth defect above 0.1% O2. O2-reductase activities of these different proteins are additive since the quadruple mutant displays a stronger phenotype when exposed to low O2 tensions compared to the triple mutants. Our results demonstrate a key role for revRbrs, FdpF, and FdpA proteins in the ability of C. difficile to grow in the presence of physiological O2 tensions such as those encountered in the colon. IMPORTANCE Although the gastrointestinal tract is regarded as mainly anoxic, low O2 tension is present in the gut and tends to increase following antibiotic-induced disruption of the host microbiota. Two decreasing O2 gradients are observed, a longitudinal one from the small to the large intestine and a second one from the intestinal epithelium toward the colon lumen. Thus, O2 concentration fluctuations within the gastrointestinal tract are a challenge for anaerobic bacteria such as C. difficile. This enteropathogen has developed efficient strategies to detoxify O2. In this work, we identified reverse rubrerythrins and flavodiiron proteins as key actors for O2 tolerance in C. difficile. These enzymes are responsible for the reduction of O2 protecting C. difficile vegetative cells from associated damages. Original and complex detoxification pathways involving O2-reductases are crucial in the ability of C. difficile to tolerate O2 and survive to O2 concentrations encountered in the gastrointestinal tract.

scholarly journals DNA Damage Kills Bacterial Spores and Cells Exposed to 222-Nanometer UV Radiation

2020 ◽  
Vol 86 (8) ◽  
Author(s):  
Willie Taylor ◽  
Emily Camilleri ◽  
D. Levi Craft ◽  
George Korza ◽  
Maria Rocha Granados ◽  
...  
Keyword(s):  
Dna Damage ◽  
Uv Radiation ◽  
Dipicolinic Acid ◽  
Dry Weight ◽  
Human Pathogens ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Pyrimidine Dimers ◽  
Repair Protein ◽  
Surface Decontamination

ABSTRACT This study examined the microbicidal activity of 222-nm UV radiation (UV222), which is potentially a safer alternative to the 254-nm UV radiation (UV254) that is often used for surface decontamination. Spores and/or growing and stationary-phase cells of Bacillus cereus, Bacillus subtilis, Bacillus thuringiensis, Staphylococcus aureus, and Clostridioides difficile and a herpesvirus were all killed or inactivated by UV222 and at lower fluences than with UV254. B. subtilis spores and cells lacking the major DNA repair protein RecA were more sensitive to UV222, as were spores lacking their DNA-protective proteins, the α/β-type small, acid-soluble spore proteins. The spore cores’ large amount of Ca2+-dipicolinic acid (∼25% of the core dry weight) also protected B. subtilis and C. difficile spores against UV222, while spores’ proteinaceous coat may have given some slight protection against UV222. Survivors among B. subtilis spores treated with UV222 acquired a large number of mutations, and this radiation generated known mutagenic photoproducts in spore and cell DNA, primarily cyclobutane-type pyrimidine dimers in growing cells and an α-thyminyl-thymine adduct termed the spore photoproduct (SP) in spores. Notably, the loss of a key SP repair protein markedly decreased spore UV222 resistance. UV222-treated B. subtilis spores germinated relatively normally, and the generation of colonies from these germinated spores was not salt sensitive. The latter two findings suggest that UV222 does not kill spores by general protein damage, and thus, the new results are consistent with the notion that DNA damage is responsible for the killing of spores and cells by UV222. IMPORTANCE Spores of a variety of bacteria are resistant to common decontamination agents, and many of them are major causes of food spoilage and some serious human diseases, including anthrax caused by spores of Bacillus anthracis. Consequently, there is an ongoing need for efficient methods for spore eradication, in particular methods that have minimal deleterious effects on people or the environment. UV radiation at 254 nm (UV254) is sporicidal and commonly used for surface decontamination but can cause deleterious effects in humans. Recent work, however, suggests that 222-nm UV (UV222) may be less harmful to people than UV254 yet may still kill bacteria and at lower fluences than UV254. The present work has identified the damage by UV222 that leads to the killing of growing cells and spores of some bacteria, many of which are human pathogens, and UV222 also inactivates a herpesvirus.

scholarly journals Bacterial Communities Associated with Surfaces of Leafy Greens: Shift in Composition and Decrease in Richness over Time

2014 ◽  
Vol 81 (4) ◽  
pp. 1530-1539 ◽  
Author(s):  
Merete Wiken Dees ◽  
Erik Lysøe ◽  
Berit Nordskog ◽  
May Bente Brurberg
Keyword(s):  
Bacterial Community ◽  
Pathogenic Bacteria ◽  
Bacterial Colonization ◽  
Bacterial Community Composition ◽  
Illumina Miseq ◽  
Human Pathogens ◽  
Content Type ◽  
Leaf Maturity ◽  
Leafy Greens ◽  
Over Time

ABSTRACTThe phyllosphere is colonized by a wide variety of bacteria and fungi; it harbors epiphytes, as well as plant-pathogenic bacteria and even human pathogens. However, little is known about how the bacterial community composition on leafy greens develops over time. The bacterial community of the leafy-green phyllosphere obtained from two plantings of rocket salad (Diplotaxis tenuifolia) and three plantings of lettuce (Lactuca sativa) at two farms in Norway were profiled by an Illumina MiSeq-based approach. We found that the bacterial richness of theL. sativasamples was significantly greater shortly (3 weeks) after planting than at harvest (5 to 7 weeks after planting) for plantings 1 and 3 at both farms. For the second planting, the bacterial diversity remained consistent at the two sites. This suggests that the effect on bacterial colonization of leaves, at least in part must, be seasonally driven rather than driven solely by leaf maturity. The distribution of phyllosphere communities varied betweenD. tenuifoliaandL. sativaat harvest. The variability between these species at the same location suggests that the leaf-dwelling bacteria are not only passive inhabitants but interact with the host, which shapes niches favoring the growth of particular taxa. This work contributes to our understanding of host plant-specific microbial community structures and shows how these communities change throughout plant development.

scholarly journals Livestock Origin for a Human Pandemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Laura E. Spoor ◽  
Paul R. McAdam ◽  
Lucy A. Weinert ◽  
Andrew Rambaut ◽  
Henrik Hasman ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pathogenic Bacteria ◽  
Control Measures ◽  
Human Populations ◽  
Epidemic Spread ◽  
Human Pathogens ◽  
Methicillin Resistant ◽  
Content Type ◽  
Evolutionary Origins ◽  
Healthy Humans

ABSTRACTThe importance of livestock as a source of bacterial pathogens with the potential for epidemic spread in human populations is unclear. In recent years, there has been a global increase in community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) infections of healthy humans, but an understanding of the different evolutionary origins of CA-MRSA clones and the basis for their recent expansion is lacking. Here, using a high-resolution phylogenetic approach, we report the discovery of two emergent clones of human epidemic CA-MRSA which resulted from independent livestock-to-human host jumps by the major bovineS. aureuscomplex, CC97. Of note, one of the new clones was isolated from human infections on four continents, demonstrating its global dissemination since the host jump occurred over 40 years ago. The emergence of both humanS. aureusclones coincided with the independent acquisition of mobile genetic elements encoding antimicrobial resistance and human-specific mediators of immune evasion, consistent with an important role for these genetic events in the capacity to survive and transmit among human populations. In conclusion, we provide evidence that livestock represent a reservoir for the emergence of new human-pathogenicS. aureusclones with the capacity for pandemic spread. These findings have major public health implications highlighting the importance of surveillance for early identification of emergent clones and improved transmission control measures at the human-livestock interface.IMPORTANCEAnimals are the major source of new pathogens affecting humans. However, the potential for pathogenic bacteria that originally were found in animals to switch hosts and become widely established in human populations is not clear. Here, we report the discovery of emergent clones of methicillin-resistantStaphylococcus aureus(MRSA) that originated in livestock and switched to humans, followed by host-adaptive evolution and epidemic spread in global human populations. Our findings demonstrate that livestock can act as a reservoir for the emergence of new human bacterial clones with potential for pandemic spread, highlighting the potential role of surveillance and biosecurity measures in the agricultural setting for preventing the emergence of new human pathogens.

scholarly journals New Host-Directed Therapeutics for the Treatment of Clostridioides difficile Infection

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Jourdan A. Andersson ◽  
Alex G. Peniche ◽  
Cristi L. Galindo ◽  
Prapaporn Boonma ◽  
Jian Sha ◽  
...  
Keyword(s):  
Immune Responses ◽  
Murine Model ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Drug Efficacy ◽  
Innate Immune ◽  
Rna Seq ◽  
Human Pathogens ◽  
Content Type ◽  
Clostridioides Difficile

ABSTRACT Frequent and excessive use of antibiotics primes patients to Clostridioides difficile infection (CDI), which leads to fatal pseudomembranous colitis, with limited treatment options. In earlier reports, we used a drug repurposing strategy and identified amoxapine (an antidepressant), doxapram (a breathing stimulant), and trifluoperazine (an antipsychotic), which provided significant protection to mice against lethal infections with several pathogens, including C. difficile. However, the mechanisms of action of these drugs were not known. Here, we provide evidence that all three drugs offered protection against experimental CDI by reducing bacterial burden and toxin levels, although the drugs were neither bacteriostatic nor bactericidal in nature and had minimal impact on the composition of the microbiota. Drug-mediated protection was dependent on the presence of the microbiota, implicating its role in evoking host defenses that promoted protective immunity. By utilizing transcriptome sequencing (RNA-seq), we identified that each drug increased expression of several innate immune response-related genes, including those involved in the recruitment of neutrophils, the production of interleukin 33 (IL-33), and the IL-22 signaling pathway. The RNA-seq data on selected genes were confirmed by quantitative real-time PCR (qRT-PCR) and protein assays. Focusing on amoxapine, which had the best anti-CDI outcome, we demonstrated that neutralization of IL-33 or depletion of neutrophils resulted in loss of drug efficacy. Overall, our lead drugs promote disease alleviation and survival in the murine model through activation of IL-33 and by clearing the pathogen through host defense mechanisms that critically include an early influx of neutrophils. IMPORTANCE Clostridioides difficile is a spore-forming anaerobic bacterium and the leading cause of antibiotic-associated colitis. With few therapeutic options and high rates of disease recurrence, the need to develop new treatment options is urgent. Prior studies utilizing a repurposing approach identified three nonantibiotic Food and Drug Administration-approved drugs, amoxapine, doxapram, and trifluoperazine, with efficacy against a broad range of human pathogens; however, the protective mechanisms remained unknown. Here, we identified mechanisms leading to drug efficacy in a murine model of lethal C. difficile infection (CDI), advancing our understanding of the role of these drugs in infectious disease pathogenesis that center on host immune responses to C. difficile. Overall, these studies highlight the crucial involvement of innate immune responses, as well as the importance of immunomodulation as a potential therapeutic option to combat CDI.

scholarly journals Deposition of Bacteria and Bacterial Spores by Bathroom Hot-Air Hand Dryers

2018 ◽  
Vol 84 (8) ◽  
pp. e00044-18 ◽  
Author(s):  
Luz del Carmen Huesca-Espitia ◽  
Jaber Aslanzadeh ◽  
Richard Feinn ◽  
Gabrielle Joseph ◽  
Thomas S. Murray ◽  
...  
Keyword(s):  
Basic Science ◽  
Pathogenic Bacteria ◽  
Basic Research ◽  
Science Research ◽  
Bacterial Spores ◽  
Human Pathogens ◽  
Content Type ◽  
Research Areas ◽  
Hot Air ◽  
Basic Science Research

ABSTRACTHot-air hand dryers in multiple men's and women's bathrooms in three basic science research areas in an academic health center were screened for their deposition on plates of (i) total bacteria, some of which were identified, and (ii) a kanamycin-resistantBacillus subtilisstrain, PS533, spores of which are produced in large amounts in one basic science research laboratory. Plates exposed to hand dryer air for 30 s averaged 18 to 60 colonies/plate; but interior hand dryer nozzle surfaces had minimal bacterial levels, plates exposed to bathroom air for 2 min with hand dryers off averaged ≤1 colony, and plates exposed to bathroom air moved by a small fan for 20 min had averages of 15 and 12 colonies/plate in two buildings tested. Retrofitting hand dryers with HEPA filters reduced bacterial deposition by hand dryers ∼4-fold, and potential human pathogens were recovered from plates exposed to hand dryer air whether or not a HEPA filter was present and from bathroom air moved by a small fan. Spore-forming colonies, identified asB. subtilisPS533, averaged ∼2.5 to 5% of bacteria deposited by hand dryers throughout the basic research areas examined regardless of distance from the spore-forming laboratory, and these were almost certainly deposited as spores. Comparable results were obtained when bathroom air was sampled for spores. These results indicate that many kinds of bacteria, including potential pathogens and spores, can be deposited on hands exposed to bathroom hand dryers and that spores could be dispersed throughout buildings and deposited on hands by hand dryers.IMPORTANCEWhile there is evidence that bathroom hand dryers can disperse bacteria from hands or deposit bacteria on surfaces, including recently washed hands, there is less information on (i) the organisms dispersed by hand dryers, (ii) whether hand dryers provide a reservoir of bacteria or simply blow large amounts of bacterially contaminated air, and (iii) whether bacterial spores are deposited on surfaces by hand dryers. Consequently, this study has implications for the control of opportunistic bacterial pathogens and spores in public environments including health care settings. Within a large building, potentially pathogenic bacteria, including bacterial spores, may travel between rooms, and subsequent bacterial/spore deposition by hand dryers is a possible mechanism for spread of infectious bacteria, including spores of potential pathogens if present.

scholarly journals Persistent Infection and Long-Term Carriage of Typhoidal and Nontyphoidal Salmonellae

2018 ◽  
Vol 32 (1) ◽  
Author(s):  
Ohad Gal-Mor
Keyword(s):  
Persistent Infection ◽  
Salmonella Enterica ◽  
Host Response ◽  
Pathogenic Bacteria ◽  
Current Knowledge ◽  
Laboratory Diagnosis ◽  
Human Pathogens ◽  
Content Type ◽  
Persistent Infections

SUMMARYThe ability of pathogenic bacteria to affect higher organisms and cause disease is one of the most dramatic properties of microorganisms. Some pathogens can establish transient colonization only, but others are capable of infecting their host for many years or even for a lifetime. Long-term infection is called persistence, and this phenotype is fundamental for the biology of important human pathogens, includingHelicobacter pylori,Mycobacterium tuberculosis, andSalmonella enterica. Both typhoidal and nontyphoidal serovars of the speciesSalmonella entericacan cause persistent infection in humans; however, as these twoSalmonellagroups cause clinically distinct diseases, the characteristics of their persistent infections in humans differ significantly. Here, following a general summary ofSalmonellapathogenicity, host specificity, epidemiology, and laboratory diagnosis, I review the current knowledge aboutSalmonellapersistence and discuss the relevant epidemiology of persistence (including carrier rate, duration of shedding, and host and pathogen risk factors), the host response toSalmonellapersistence,Salmonellagenes involved in this lifestyle, as well as genetic and phenotypic changes acquired during prolonged infection within the host. Additionally, I highlight differences between the persistence of typhoidal and nontyphoidalSalmonellastrains in humans and summarize the current gaps and limitations in our understanding, diagnosis, and curing of persistentSalmonellainfections.

scholarly journals In Vitro Activity of Omadacycline, a New Tetracycline Analog, and Comparators against Clostridioides difficile

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Khurshida Begum ◽  
Eugénie Bassères ◽  
Julie Miranda ◽  
Chris Lancaster ◽  
Anne J. Gonzales-Luna ◽  
...  
Keyword(s):  
Large Scale ◽  
Anaerobic Bacteria ◽  
Oral Antibiotic ◽  
Content Type ◽  
Microdilution Method ◽  
Clostridioides Difficile ◽  
Broth Microdilution Method ◽  
Time Kill ◽  
Further Development

ABSTRACT Omadacycline is a potent aminomethylcycline with in vitro activity against Gram-positive, Gram-negative, and anaerobic bacteria. Preliminary data demonstrated that omadacycline has in vitro activity against Clostridioides difficile; however, large-scale in vitro studies have not been done. The purpose of this study was to assess the in vitro susceptibility of omadacycline and comparators on a large biobank of clinical C. difficile isolates. In vitro C. difficile susceptibility to omadacycline and comparators (fidaxomicin, metronidazole, and vancomycin) was assessed using the broth microdilution method. Minimum bactericidal concentrations (MBCs) and time-kill assays were assessed for pharmacodynamics analysis, and whole-genome sequencing was performed in a subset of isolates to assess distribution of MICs and resistance determinants. Two hundred fifty clinical C. difficile isolates collected between 2015 and 2018 were tested for in vitro susceptibility of omadacycline and comparators. Ribotypes included F001 (n = 5), F002 (n = 56), F014-020 (n = 66), F017 (n = 8), F027 (n = 53), F106 (n = 45), and F255 (n = 17). Omadacycline demonstrated potent in vitro activity with an MIC range of 0.016 to 0.13 μg/ml, an MIC50 of 0.031 μg/ml, and an MIC90 of 0.031 μg/ml. No difference was observed for omadacycline MIC50 and MIC90 values stratified by ribotype, disease severity, or vancomycin susceptibility. Bactericidal activity was confirmed in time-kill studies. No difference was observed in MIC based on C. difficile phylogeny. Further development of omadacycline as an intravenous and oral antibiotic directed toward C. difficile infection is warranted.

scholarly journals Bacillus subtilis-Mediated Protection from Citrobacter rodentium-Associated Enteric Disease RequiresespHand Functional Flagella

2011 ◽  
Vol 80 (2) ◽  
pp. 710-719 ◽  
Author(s):  
Sara E. Jones ◽  
Katherine L. Knight
Keyword(s):  
Bacillus Subtilis ◽  
Pathogenic Bacteria ◽  
Cell Loss ◽  
Enteric Infection ◽  
Citrobacter Rodentium ◽  
Human Pathogens ◽  
Wild Type ◽  
Content Type ◽  
Beneficial Microbes ◽  
Pathogen Colonization

ABSTRACTCommensals limit disease caused by invading pathogens; however, the mechanisms and genes utilized by beneficial microbes to inhibit pathogenesis are poorly understood. The attaching and effacing mouse pathogenCitrobacter rodentiumassociates intimately with the intestinal epithelium, and infections result in acute colitis.C. rodentiumis used to model the human pathogens enterohemorrhagicEscherichia coliand enteropathogenicE. coli. To confirm thatBacillus subtilis, a spore-forming bacterium found in the gut of mammals, could reduceC. rodentium-associated disease, mice received wild-typeB. subtilisspores and 24 h later were infected by oral gavage with pathogenicC. rodentium. Disease was assessed by determining the extent of colonic epithelial hyperplasia, goblet cell loss, diarrhea, and pathogen colonization. Mice that received wild-typeB. subtilisprior to enteric infection were protected from disease even thoughC. rodentiumcolonization was not inhibited. In contrast,espHandhagmutants, defective in exopolysaccharides and flagellum production, respectively, did not protect mice fromC. rodentium-associated disease. AmotABmutant also failed to protect mice from disease, suggesting thatB. subtilis-mediated protection requires functional flagella. By expanding our current mechanistic knowledge of bacterial protection, we can better utilize beneficial microbes to prevent intestinal disease caused by pathogenic bacteria, ultimately reducing human disease. Our data demonstrate that wild-typeB. subtilisreduced disease caused byC. rodentiuminfection through a mechanism that requiredespHand functional flagella.

Sign in / Sign up

Export Citation Format

Share Document