scholarly journals H2S and reactive sulfur signaling at the host-bacterial pathogen interface

2020 ◽  
Vol 295 (38) ◽  
pp. 13150-13168 ◽  
Author(s):  
Brenna J. C. Walsh ◽  
David P. Giedroc
Keyword(s):  
Bacterial Pathogen ◽  
Invasive Disease ◽  
Bacterial Cells ◽  
Bacterial Survival ◽  
Post Translational Modification ◽  
Sulfur Species ◽  
Transcriptional Regulatory ◽  
Important Player ◽  
Infected Cells ◽  
Regulatory Significance

Bacterial pathogens that cause invasive disease in the vertebrate host must adapt to host efforts to cripple their viability. Major host insults are reactive oxygen and reactive nitrogen species as well as cellular stress induced by antibiotics. Hydrogen sulfide (H2S) is emerging as an important player in cytoprotection against these stressors, which may well be attributed to downstream more oxidized sulfur species termed reactive sulfur species (RSS). In this review, we summarize recent work that suggests that H2S/RSS impacts bacterial survival in infected cells and animals. We discuss the mechanisms of biogenesis and clearance of RSS in the context of a bacterial H2S/RSS homeostasis model and the bacterial transcriptional regulatory proteins that act as “sensors” of cellular RSS that maintain H2S/RSS homeostasis. In addition, we cover fluorescence imaging– and MS–based approaches used to detect and quantify RSS in bacterial cells. Last, we discuss proteome persulfidation (S-sulfuration) as a potential mediator of H2S/RSS signaling in bacteria in the context of the writer-reader-eraser paradigm, and progress toward ascribing regulatory significance to this widespread post-translational modification.

scholarly journals Radiation-Inactivated Acinetobacter baumannii Vaccine Candidates

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 96
Author(s):  
Stephen J. Dollery ◽  
Daniel V. Zurawski ◽  
Elena K. Gaidamakova ◽  
Vera Y. Matrosova ◽  
John K. Tobin ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
Bacterial Cells ◽  
Wound Infections ◽  
Protein Profiles ◽  
Vaccine Candidates ◽  
Rich Media ◽  
Life Threatening

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection.

Pseudomonas aeruginosa Oligoribonuclease Controls Susceptibility to Polymyxin B by Regulating Pel Exopolysaccharide Production

2022 ◽  
Author(s):  
Baopeng Yang ◽  
Yujun Jiang ◽  
Yongxin Jin ◽  
Fang Bai ◽  
Zhihui Cheng ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Resistance ◽  
Defense Mechanism ◽  
Extracellular Polysaccharide ◽  
Opportunistic Pathogen ◽  
Polymyxin B ◽  
Guanosine Monophosphate ◽  
Extracellular Dna ◽  
Bacterial Cells ◽  
Bacterial Survival

Polymyxins are considered as the last resort antibiotics to treat infections caused by multidrug-resistant Gram negative pathogens. Pseudomonas aeruginosa is an opportunistic pathogen that causes various infections in humans. Proteins involved in lipopolysaccharide modification and maintaining inner and outer membrane integrities have been found to contribute to the bacterial resistance to polymyxins. Oligoribonuclease (Orn) is an exonuclease that regulates the homeostasis of intracellular (3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), thereby regulating the production of extracellular polysaccharide in P. aeruginosa . Previously, we demonstrated that Orn affects the bacterial resistance to fluoroquinolone, β-lactam and aminoglycoside antibiotics. In this study, we found that mutation of orn increased the bacterial survival following polymyxin B treatment in a wild type P. aeruginosa strain PA14. Overexpression of c-di-GMP degradation enzymes in the orn mutant reduced the bacterial survival. By using a fluorescence labeled polymyxin B, we found that mutation of orn increased the bacterial surface bound polymyxin B. Deletion of the Pel synthesis genes or treatment with a Pel hydrolase reduced the surface bound polymyxin B and bacterial survival. We further demonstrated that Pel binds to extracellular DNA (eDNA), which traps polymyxin B and thus protects the bacterial cells. Collectively, our results revealed a novel defense mechanism against polymyxin in P. aeruginosa .

scholarly journals Investigation of orf virus structure and morphogenesis using recombinants expressing FLAG-tagged envelope structural proteins: evidence for wrapped virus particles and egress from infected cells

2009 ◽  
Vol 90 (3) ◽  
pp. 614-625 ◽  
Author(s):  
Joanne L. Tan ◽  
Norihito Ueda ◽  
Andrew A. Mercer ◽  
Stephen B. Fleming
Keyword(s):  
Fluorescent Microscopy ◽  
Cellular Membrane ◽  
Immunogold Labelling ◽  
Orf Virus ◽  
Structural Proteins ◽  
Post Translational Modification ◽  
Virus Particles ◽  
Viral Egress ◽  
Infected Cells ◽  
Almost All

Orf virus (ORFV) is the type species of the genus Parapoxvirus, but little is known about the structure or morphogenesis of the virus. In contrast, the structure and morphogenesis of vaccinia virus (VACV) has been extensively studied. VACV has two main infectious forms, mature virion (MV) and extracellular virion (EV). The MV is wrapped by two additional membranes derived from the trans-Golgi to produce a wrapped virion (WV), the outermost of which is lost by cellular membrane fusion during viral egress to form the EV. Genome sequencing of ORFV has revealed that it has homologues of almost all of the VACV structural genes. Notable exceptions are A36R, K2L, A56R and B5R, which are associated with WV and EV envelopes. This study investigated the morphogenesis and structure of ORFV by fusing FLAG peptide to the structural proteins 10 kDa, F1L and ORF-110 to form recombinant viruses. 10 kDa and F1L are homologues of VACV A27L and H3L MV membrane proteins, whilst ORF-110 is homologous to VACV A34R, an EV membrane protein. Immunogold labelling of FLAG proteins on virus particles isolated from lysed cells showed that FLAG–F1L and FLAG–10 kDa were displayed on the surface of infectious particles, whereas ORF-110–FLAG could not be detected. Western blot analysis of solubilized recombinant ORF-110–FLAG particles revealed that ORF-110–FLAG was abundant and undergoes post-translational modification indicative of endoplasmic reticulum trafficking. Fluorescent microscopy confirmed the prediction that ORF-110–FLAG localized to the Golgi in virus-infected cells. Finally, immunogold labelling of EVs showed that ORF-110–FLAG became exposed on the surface of EV-like particles as a result of egress from the cell.

scholarly journals Consensus transcriptional regulatory networks of coronavirus-infected human cells

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Scott A. Ochsner ◽  
Rudolf T. Pillich ◽  
Neil J. McKenna
Keyword(s):  
Signaling Pathways ◽  
Regulatory Networks ◽  
Data Exchange ◽  
Epithelial To Mesenchymal Transition ◽  
Transcriptional Regulatory Networks ◽  
Mesenchymal Transition ◽  
Human Genes ◽  
Transcriptional Regulatory ◽  
Infected Cells ◽  
Key Drivers

Abstract Establishing consensus around the transcriptional interface between coronavirus (CoV) infection and human cellular signaling pathways can catalyze the development of novel anti-CoV therapeutics. Here, we used publicly archived transcriptomic datasets to compute consensus regulatory signatures, or consensomes, that rank human genes based on their rates of differential expression in MERS-CoV (MERS), SARS-CoV-1 (SARS1) and SARS-CoV-2 (SARS2)-infected cells. Validating the CoV consensomes, we show that high confidence transcriptional targets (HCTs) of MERS, SARS1 and SARS2 infection intersect with HCTs of signaling pathway nodes with known roles in CoV infection. Among a series of novel use cases, we gather evidence for hypotheses that SARS2 infection efficiently represses E2F family HCTs encoding key drivers of DNA replication and the cell cycle; that progesterone receptor signaling antagonizes SARS2-induced inflammatory signaling in the airway epithelium; and that SARS2 HCTs are enriched for genes involved in epithelial to mesenchymal transition. The CoV infection consensomes and HCT intersection analyses are freely accessible through the Signaling Pathways Project knowledgebase, and as Cytoscape-style networks in the Network Data Exchange repository.

scholarly journals Evolution and Sequence Diversity of FhuA inSalmonellaandEscherichia

2018 ◽  
Vol 86 (11) ◽  
Author(s):  
Yejun Wang ◽  
Xiongbin Chen ◽  
Yueming Hu ◽  
Guoqiang Zhu ◽  
Aaron P. White ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Comparative Sequence Analysis ◽  
Sequence Diversity ◽  
Bacterial Cells ◽  
Bacterial Survival ◽  
Bacterial Strains ◽  
Content Type ◽  
High Conservation ◽  
High Selection ◽  
Clustering Pattern

ABSTRACTThefhuACDBoperon, present in a number ofEnterobacteriaceae, encodes components essential for the uptake of ferric hydroxamate type siderophores. FhuA acts not only as a transporter for physiologically important chelated ferric iron but also as a receptor for various bacteriophages, toxins, and antibiotics, which are pathogenic to bacterial cells. In this research,fhuAgene distribution and sequence diversity were investigated inEnterobacteriaceae, especiallySalmonellaandEscherichia. Comparative sequence analysis resulted in afhuAphylogenetic tree that did not match the expected phylogeny of species or trees of thefhuCDBgenes. ThefhuAsequences showed a unique mosaic clustering pattern. On the other hand, the gene sequences showed high conservation for strains from the same serovar or serotype. In total, six clusters were identified from FhuA proteins inSalmonellaandEscherichia, among which typical peptide fragment variations could be defined. Six fragmental insertions/deletions and two substitution fragments were discovered, for which the combination of polymorphism patterns could well classify the different clusters. Structural modeling demonstrated that all the six featured insertions/deletions and one substitution fragment are located at the apexes of the long loops present as part of the FhuA external pocket. These frequently mutated regions are likely under high selection pressure, with bacterial strains balancing escape from phage infection or toxin/antibiotics attack viafhuAgene mutations while maintaining the siderophore uptake activity essential for bacterial survival. The unusualfhuAclustering suggests that high-frequency exchange offhuAgenes has occurred between enterobacterial strains after distinctive species were established.

scholarly journals Compartmentalization of the Broad-Range Phospholipase C Activity to the Spreading Vacuole Is Critical for Listeria monocytogenes Virulence

2006 ◽  
Vol 75 (1) ◽  
pp. 44-51 ◽  
Author(s):  
P. S. Marie Yeung ◽  
Yoojin Na ◽  
Amanda J. Kreuder ◽  
Hélène Marquis
Keyword(s):  
Listeria Monocytogenes ◽  
Phospholipase C ◽  
Membrane Damage ◽  
Bacterial Pathogen ◽  
Host Cells ◽  
Virulence Attenuation ◽  
Infected Cells ◽  
Host Cell Membranes ◽  
Cell Spread

ABSTRACT Listeria monocytogenes is a bacterial pathogen that multiplies in the cytosol of host cells and spreads directly from cell to cell by using an actin-based mechanism of motility. The broad-range phospholipase C (PC-PLC) of L. monocytogenes contributes to bacterial escape from vacuoles formed upon cell-to-cell spread. PC-PLC is made as an inactive proenzyme whose activation requires cleavage of an N-terminal propeptide. During infection, PC-PLC is activated specifically in acidified vacuoles. To assess the importance of compartmentalizing PC-PLC activity during infection, we created a mutant that makes constitutively active PC-PLC (the plcBΔpro mutant). Results from intracellular growth and cell-to-cell spread assays showed that the plcBΔpro mutant was sensitive to gentamicin, suggesting that unregulated PC-PLC activity causes damage to host cell membranes. This was confirmed by the observation of a twofold increase in staining of live infected cells by a non-membrane-permeant DNA fluorescent dye. However, membrane damage was not sufficient to cause cell lysis and was dependent on bacterial cell-to-cell spread, suggesting that damage was localized to bacterium-containing filopodia. Using an in vivo competitive infection assay, we observed that the plcBΔpro mutant was outcompeted up to 200-fold by the wild-type strain in BALB/c mice. Virulence attenuation was greater when mice were infected orally than when they were infected intravenously, presumably because the plcBΔpro mutant was initially outcompeted in the intestines, reducing the number of mutant bacteria reaching the liver and spleen. Together, these results emphasize the importance for L. monocytogenes virulence of compartmentalizing the activity of PC-PLC during infection.

scholarly journals Silencing of Host Cell CYBB Gene Expression by the Nuclear Effector AnkA of the Intracellular Pathogen Anaplasma phagocytophilum

2009 ◽  
Vol 77 (6) ◽  
pp. 2385-2391 ◽  
Author(s):  
Jose C. Garcia-Garcia ◽  
Kristen E. Rennoll-Bankert ◽  
Shaaretha Pelly ◽  
Aaron M. Milstone ◽  
J. Stephen Dumler
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Anaplasma Phagocytophilum ◽  
Host Cells ◽  
Bacterial Survival ◽  
Defense Genes ◽  
Regulatory Regions ◽  
Transcriptional Regulatory ◽  
Cell Gene Expression ◽  
Host Chromatin

ABSTRACT Coevolution of intracellular bacterial pathogens and their host cells resulted in the appearance of effector molecules that when translocated into the host cell modulate its function, facilitating bacterial survival within the hostile host environment. Some of these effectors interact with host chromatin and other nuclear components. In this report, we show that the AnkA protein of Anaplasma phagocytophilum, which is translocated into the host cell nucleus, interacts with gene regulatory regions of host chromatin and is involved in downregulating expression of CYBB (gp91 phox ) and other key host defense genes. AnkA effector protein rapidly accumulated in nuclei of infected cells coincident with changes in CYBB transcription. AnkA interacted with transcriptional regulatory regions of the CYBB locus at sites where transcriptional regulators bind. AnkA binding to DNA occurred at regions with high AT contents. Mutation of AT stretches at these sites abrogated AnkA binding. Histone H3 acetylation decreased dramatically at the CYBB locus during A. phagocytophilum infection, particularly around AnkA binding sites. Transcription of CYBB and other defense genes was significantly decreased in AnkA-transfected HL-60 cells. These data suggest a mechanism by which intracellular pathogens directly regulate host cell gene expression mediated by nuclear effectors and changes in host chromatin structure.

scholarly journals EseE of Edwardsiella tarda Augments Secretion of Translocon Protein EseC and Expression of theescC-eseEOperon

2016 ◽  
Vol 84 (8) ◽  
pp. 2336-2344 ◽  
Author(s):  
Jia Yi ◽  
Shui Bing Xiao ◽  
Zhi Xiong Zeng ◽  
Jin Fang Lu ◽  
Lu Yi Liu ◽  
...  
Keyword(s):  
Gel Filtration ◽  
Host Cells ◽  
Edwardsiella Tarda ◽  
Supernatant Fraction ◽  
Bacterial Cells ◽  
Bacterial Survival ◽  
Content Type ◽  
Chaperone Protein ◽  
Pulldown Assay ◽  
Novel Protein

Edwardsiella tardais an important Gram-negative pathogen that employs a type III secretion system (T3SS) to deliver effectors into host cells to facilitate bacterial survival and replication. These effectors are translocated into host cells through a translocon complex composed of three secreted proteins, namely, EseB, EseC, and EseD. The secretion of EseB and EseD requires a chaperone protein called EscC, whereas the secretion of EseC requires the chaperone EscA. In this study, we identified a novel protein (EseE) that also regulates the secretion of EseC. AneseEdeletion mutant secreted much less EseC into supernatants, accompanied by increased EseC levels within bacterial cells. We also demonstrated that EseE interacted directly with EseC in a pulldown assay. Interestingly, EseC, EseE, and EscA were able to form a ternary complex, as revealed by pulldown and gel filtration assays. Of particular importance, the deletion ofeseEresulted in decreased levels of EseB and EseD proteins in both the bacterial pellet and supernatant fraction. Furthermore, real-time PCR assays showed that EseE positively regulated the transcription of the translocon operonescC-eseE, comprisingescC,eseB,escA,eseC,eseD, andeseE. These effects of EseE on the translocon components/operon appeared to have a functional consequence, since the ΔeseEstrain was outcompeted by wild-typeE. tardain a mixed infection in blue gourami fish. Collectively, our results demonstrate that EseE not only functions as a chaperone for EseC but also acts as a positive regulator controlling the expression of the translocon operonescC-eseE, thus contributing to the pathogenesis ofE. tardain fish.

scholarly journals Identification of a GrgA-Euo-HrcA Transcriptional Regulatory Network in Chlamydia

mSystems ◽  
2021 ◽  
Author(s):  
Wurihan Wurihan ◽  
Yi Zou ◽  
Alec M. Weber ◽  
Korri Weldon ◽  
Yehong Huang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Regulatory Network ◽  
Transcriptional Regulatory Network ◽  
Bacterial Pathogen ◽  
Developed Countries ◽  
Developmental Cycle ◽  
Content Type ◽  
Sexually Transmitted ◽  
Transcriptional Regulatory ◽  
Preventable Blindness

Chlamydia trachomatis is the most prevalent sexually transmitted bacterial pathogen worldwide and is a leading cause of preventable blindness in underdeveloped areas as well as some developed countries. Chlamydia carries genes that encode a limited number of known transcription factors. While Euo is thought to be critical for early chlamydial development, the functions of GrgA and HrcA in the developmental cycle are unclear.

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