scholarly journals Listeria monocytogenes requires cellular respiration for NAD+ regeneration and pathogenesis

2021 ◽  
Author(s):  
Rafael Rivera-Lugo ◽  
David Deng ◽  
Andrea Anaya-Sanchez ◽  
Sara Tejedor-Sanz ◽  
Valeria M Reyes Ruiz ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Oxidative Phosphorylation ◽  
Nadh Oxidase ◽  
Cellular Respiration ◽  
Bacterial Respiration ◽  
Infection Model ◽  
Primary Role ◽  
Growth Defects ◽  
Mouse Infection Model

Cellular respiration is essential for multiple bacterial pathogens and a validated antibiotic target. In addition to driving oxidative phosphorylation, bacterial respiration has a variety of ancillary functions that obscure its contribution to pathogenesis. We find here that the intracellular pathogen Listeria monocytogenes encodes two respiratory pathways which are partially functionally redundant and indispensable for pathogenesis. Loss of respiration decreased NAD+ regeneration, but this could be specifically reversed by heterologous expression of a water-forming NADH oxidase (NOX). NOX expression fully rescued intracellular growth defects and increased L. monocytogenes loads >1,000-fold in a mouse infection model. Consistent with NAD+ regeneration maintaining L. monocytogenes viability and enabling immune evasion, a respiration-deficient strain exhibited elevated bacteriolysis within the host cytosol and NOX rescued this phenotype. These studies show that NAD+ regeneration, rather than oxidative phosphorylation, represents the primary role of L. monocytogenes respiration and highlight the nuanced relationship between bacterial metabolism, physiology, and pathogenesis.

scholarly journals Identification and Characterization of Di- and Tripeptide Transporter DtpT of Listeria monocytogenes EGD-e

2005 ◽  
Vol 71 (10) ◽  
pp. 5771-5778 ◽  
Author(s):  
Jeroen A. Wouters ◽  
Torsten Hain ◽  
Ajub Darji ◽  
Eric Hüfner ◽  
Henrike Wemekamp-Kamphuis ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Opportunistic Infections ◽  
Essential Amino Acids ◽  
Defined Medium ◽  
Infection Model ◽  
Intracellular Pathogen ◽  
Mouse Infection Model ◽  
Stress Protection ◽  
Identification And Characterization

ABSTRACT Listeria monocytogenes is a gram-positive intracellular pathogen responsible for opportunistic infections in humans and animals. Here we identified and characterized the dtpT gene (lmo0555) of L. monocytogenes EGD-e, encoding the di- and tripeptide transporter, and assessed its role in growth under various environmental conditions as well as in the virulence of L. monocytogenes. Uptake of the dipeptide Pro-[14C]Ala was mediated by the DtpT transporter and was abrogated in a ΔdtpT isogenic deletion mutant. The DtpT transporter was shown to be required for growth when the essential amino acids leucine and valine were supplied as peptides. The protective effect of glycine- and proline-containing peptides during growth in defined medium containing 3% NaCl was noted only in L. monocytogenes EGD-e, not in the ΔdtpT mutant strain, indicating that the DtpT transporter is involved in salt stress protection. Infection studies showed that DtpT contributes to pathogenesis in a mouse infection model but has no role in bacterial growth following infection of J774 macrophages. These studies reveal that DptT may contribute to the virulence of L. monocytogenes.

Role of prophylactic azithromycin to reduce airway inflammation and mortality in a RSV mouse infection model

2018 ◽  
Vol 53 (5) ◽  
pp. 567-574 ◽  
Author(s):  
Ricardo A. Mosquera ◽  
Wilfredo De Jesus-Rojas ◽  
James M. Stark ◽  
Aravind Yadav ◽  
Cindy K. Jon ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Infection Model ◽  
Mouse Infection Model ◽  
Mouse Infection

scholarly journals Generation of Attenuated Mycobacterium bovis Strains by Signature-Tagged Mutagenesis for Discovery of Novel Vaccine Candidates

2005 ◽  
Vol 73 (4) ◽  
pp. 2379-2386 ◽  
Author(s):  
Desmond M. Collins ◽  
Bronwyn Skou ◽  
Stefan White ◽  
Shalome Bassett ◽  
Lauren Collins ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Bovis ◽  
Guinea Pigs ◽  
Essential Role ◽  
Immunoblot Analysis ◽  
Infection Model ◽  
Vaccine Candidates ◽  
Mouse Infection Model ◽  
Potential Vaccine

ABSTRACT Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex, has a particularly wide host range and causes tuberculosis in most mammals, including humans. A signature tag mutagenesis approach, which employed illegitimate recombination and infection of guinea pigs, was applied to M. bovis to discover genes important for virulence and to find potential vaccine candidates. Fifteen attenuated mutants were identified, four of which produced no lesions when inoculated separately into guinea pigs. One of these four mutants had nine deleted genes including mmpL4 and sigK and, in guinea pigs with aerosol challenge, provided protection against tuberculosis at least equal to that of M. bovis BCG. Seven mutants had mutations near the esxA (esat-6) locus, and immunoblot analysis of these confirmed the essential role of other genes at this locus in the secretion of EsxA (ESAT-6) and EsxB (CFP10). Mutations in the eight other attenuated mutants were widely spread through the chromosome and included pks1, which is naturally inactivated in clinical strains of M. tuberculosis. Many genes identified were different from those found by signature tag mutagenesis of M. tuberculosis by use of a mouse infection model and illustrate how the use of different approaches enables identification of a wider range of attenuating mutants.

scholarly journals Mutations of the Listeria monocytogenes PeptidoglycanN-Deacetylase andO-Acetylase Result in Enhanced Lysozyme Sensitivity, Bacteriolysis, and Hyperinduction of Innate Immune Pathways

2011 ◽  
Vol 79 (9) ◽  
pp. 3596-3606 ◽  
Author(s):  
Chris S. Rae ◽  
Aimee Geissler ◽  
Paul C. Adamson ◽  
Daniel A. Portnoy
Keyword(s):  
Listeria Monocytogenes ◽  
Transcriptional Responses ◽  
Gram Positive ◽  
Content Type ◽  
Growth Defects ◽  
Gram Positive Bacteria ◽  
Host Cell Death

ABSTRACTListeria monocytogenesis a Gram-positive intracellular pathogen that is naturally resistant to lysozyme. Recently, it was shown that peptidoglycan modification by N-deacetylation or O-acetylation confers resistance to lysozyme in various Gram-positive bacteria, includingL. monocytogenes.L. monocytogenespeptidoglycan is deacetylated by the action ofN-acetylglucosamine deacetylase (Pgd) and acetylated byO-acetylmuramic acid transferase (Oat). We characterized Pgd−, Oat−, and double mutants to determine the specific role ofL. monocytogenespeptidoglycan acetylation in conferring lysozyme sensitivity during infection of macrophages and mice. Pgd−and Pgd−Oat−double mutants were attenuated approximately 2 and 3.5 logs, respectively,in vivo. In bone-marrow derived macrophages, the mutants demonstrated intracellular growth defects and increased induction of cytokine transcriptional responses that emanated from a phagosome and the cytosol. Lysozyme-sensitive mutants underwent bacteriolysis in the macrophage cytosol, resulting in AIM2-dependent pyroptosis. Each of thein vitrophenotypes was rescued upon infection of LysM−macrophages. The addition of extracellular lysozyme to LysM−macrophages restored cytokine induction, host cell death, andL. monocytogenesgrowth inhibition. This surprising observation suggests that extracellular lysozyme can access the macrophage cytosol and act on intracellular lysozyme-sensitive bacteria.

scholarly journals A hybrid sub-lineage of Listeria monocytogenes comprising hypervirulent isolates

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yuelan Yin ◽  
Hao Yao ◽  
Swapnil Doijad ◽  
Suwei Kong ◽  
Yang Shen ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Virulence Genes ◽  
Teichoic Acid ◽  
Foodborne Pathogen ◽  
Bacterial Invasion ◽  
Infection Model ◽  
Wall Teichoic Acid ◽  
Mouse Infection Model ◽  
Highly Virulent ◽  
Organ Colonization

Abstract The foodborne pathogen Listeria monocytogenes (Lm) is a highly heterogeneous species and currently comprises of 4 evolutionarily distinct lineages. Here, we characterize isolates from severe ovine listeriosis outbreaks that represent a hybrid sub-lineage of the major lineage II (HSL-II) and serotype 4h. HSL-II isolates are highly virulent and exhibit higher organ colonization capacities than well-characterized hypervirulent strains of Lm in an orogastric mouse infection model. The isolates harbour both the Lm Pathogenicity Island (LIPI)-1 and a truncated LIPI-2 locus, encoding sphingomyelinase (SmcL), a virulence factor required for invasion and bacterial translocation from the gut, and other non-contiguous chromosomal segments from another pathogenic species, L. ivanovii. HSL-II isolates exhibit a unique wall teichoic acid (WTA) structure essential for resistance to antimicrobial peptides, bacterial invasion and virulence. The discovery of isolates harbouring pan-species virulence genes of the genus Listeria warrants global efforts to identify further hypervirulent lineages of Lm.

Microcycle conidiation in pycnidial cirrhii of Phomopsis viticola Sacc. Induced by elemental sulfur

1983 ◽  
Vol 29 (2) ◽  
pp. 179-184 ◽  
Author(s):  
R. Pezet ◽  
V. Pont ◽  
F. Girardet
Keyword(s):  
Oxidative Phosphorylation ◽  
Elemental Sulfur ◽  
Synthetic Medium ◽  
Cellular Respiration ◽  
Biological Cycle ◽  
Phomopsis Viticola ◽  
Differentiation Inducer ◽  
Microcycle Conidiation

On a synthetic medium containing elemental sulfur (SMGS), the growth of Phomopsis viticola Sacc. decreased considerably but pycnidia formation was highly stimulated. Secondary pycnidia, developed from spores in the cirrhii themselves, were observed. Formation of pycnidia directly from spores can be described as a microcycle stage. The role of endogenous elemental sulfur in P. viticola as a differentiation inducer in the biological cycle of the fungus is discussed on the basis of the action of elemental sulfur on cellular respiration and oxidative phosphorylation.

scholarly journals Essential Role of Invasin for Colonization and Persistence of Yersinia enterocolitica in Its Natural Reservoir Host, the Pig

2013 ◽  
Vol 82 (3) ◽  
pp. 960-969 ◽  
Author(s):  
Julia Schaake ◽  
Anna Drees ◽  
Petra Grüning ◽  
Frank Uliczka ◽  
Fabio Pisano ◽  
...  
Keyword(s):  
Yersinia Enterocolitica ◽  
Reservoir Host ◽  
Infection Model ◽  
Minor Effect ◽  
Primary Role ◽  
Pathogenic Potential ◽  
Content Type ◽  
A Minor

ABSTRACTIn this study, an oral minipig infection model was established to investigate the pathogenicity ofYersinia enterocoliticabioserotype 4/O:3. O:3 strains are highly prevalent in pigs, which are usually symptomless carriers, and they represent the most common cause of human yersiniosis. To assess the pathogenic potential of the O:3 serotype, we compared the colonization properties ofY. enterocoliticaO:3 with O:8, a highly mouse-virulentY. enterocoliticaserotype, in minipigs and mice. We found that O:3 is a significantly better colonizer of swine than is O:8. Coinfection studies with O:3 mutant strains demonstrated that small variations within the O:3 genome leading to higher amounts of the primary adhesion factor invasin (InvA) improved colonization and/or survival of this serotype in swine but had only a minor effect on the colonization of mice. We further demonstrated that a deletion of theinvAgene abolished long-term colonization in the pigs. Our results indicate a primary role for invasin in naturally occurringY. enterocoliticaO:3 infections in pigs and reveal a higher adaptation of O:3 than O:8 strains to their natural pig reservoir host.

scholarly journals RegAB Homolog of Burkholderia pseudomallei is the Master Regulator of Redox Control and involved in Virulence

2021 ◽  
Vol 17 (5) ◽  
pp. e1009604
Author(s):  
Julia Phenn ◽  
Jan Pané-Farré ◽  
Nikolai Meukow ◽  
Annelie Klein ◽  
Anne Troitzsch ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Anaerobic Growth ◽  
Infection Model ◽  
Master Regulator ◽  
Hypoxic Conditions ◽  
Mouse Infection Model ◽  
Denitrification Process

Burkholderia pseudomallei, the etiological agent of melioidosis in humans and animals, often occupies environmental niches and infection sites characterized by limited concentrations of oxygen. Versatile genomic features enable this pathogen to maintain its physiology and virulence under hypoxia, but the crucial regulatory networks employed to switch from oxygen dependent respiration to alternative terminal electron acceptors (TEA) like nitrate, remains poorly understood. Here, we combined a Tn5 transposon mutagenesis screen and an anaerobic growth screen to identify a two-component signal transduction system with homology to RegAB. We show that RegAB is not only essential for anaerobic growth, but also for full virulence in cell lines and a mouse infection model. Further investigations of the RegAB regulon, using a global transcriptomic approach, identified 20 additional regulators under transcriptional control of RegAB, indicating a superordinate role of RegAB in the B. pseudomallei anaerobiosis regulatory network. Of the 20 identified regulators, NarX/L and a FNR homolog were selected for further analyses and a role in adaptation to anaerobic conditions was demonstrated. Growth experiments identified nitrate and intermediates of the denitrification process as the likely signal activateing RegAB, NarX/L, and probably of the downstream regulators Dnr or NsrR homologs. While deletions of individual genes involved in the denitrification process demonstrated their important role in anaerobic fitness, they showed no effect on virulence. This further highlights the central role of RegAB as the master regulator of anaerobic metabolism in B. pseudomallei and that the complete RegAB-mediated response is required to achieve full virulence. In summary, our analysis of the RegAB-dependent modulon and its interconnected regulons revealed a key role for RegAB of B. pseudomallei in the coordination of the response to hypoxic conditions and virulence, in the environment and the host.

scholarly journals Periplasmic Superoxide Dismutase in Meningococcal Pathogenicity

1998 ◽  
Vol 66 (1) ◽  
pp. 213-217 ◽  
Author(s):  
Kathryn E. Wilks ◽  
Kate L. R. Dunn ◽  
Jayne L. Farrant ◽  
Karen M. Reddin ◽  
Andrew R. Gorringe ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Free Radicals ◽  
Superoxide Radical ◽  
Infection Model ◽  
Wild Type ◽  
Superoxide Radical Anion ◽  
Mouse Infection Model ◽  
Increased Sensitivity ◽  
Hydroxyl Free Radicals

ABSTRACT Meningococcal sodC encodes periplasmic copper- and zinc-cofactored superoxide dismutase (Cu,Zn SOD) which catalyzes the conversion of the superoxide radical anion to hydrogen peroxide, preventing a sequence of reactions leading to production of toxic hydroxyl free radicals. From its periplasmic location, Cu,Zn SOD was inferred to acquire its substrate from outside the bacterial cell and was speculated to play a role in preserving meningococci from the action of microbicidal oxygen free radicals produced in the context of host defense. A sodC mutant was constructed by allelic exchange and was used to investigate the role of Cu,Zn SOD in pathogenicity. Wild-type and mutant meningococci grew at comparable rates and survived equally long in aerobic liquid culture. The mutant showed no increased sensitivity to paraquat, which generates superoxide within the cytosol, but was approximately 1,000-fold more sensitive to the toxicity of superoxide generated in solution by the xanthine/xanthine oxidase system. These data support a role for meningococcal Cu,Zn SOD in protection against exogenous superoxide. In experiments to translate this into a role in pathogenicity, wild-type and mutant organisms were used in an intraperitoneal mouse infection model. The sodC mutant was significantly less virulent. We conclude that periplasmic Cu,Zn SOD contributes to the virulence ofNeisseria meningitidis, most likely by reducing the effectiveness of toxic oxygen host defenses.

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