scholarly journals Role of PstS in the Pathogenesis of Acinetobacter baumannii Under Microaerobiosis and Normoxia

2020 ◽  
Vol 222 (7) ◽  
pp. 1204-1212
Author(s):  
María Luisa Gil-Marqués ◽  
Gema Labrador Herrera ◽  
Andrea Miró Canturri ◽  
Jerónimo Pachón ◽  
Younes Smani ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Virulence Factor ◽  
Lethal Dose ◽  
A549 Cells ◽  
Wild Type ◽  
Colony Forming Units ◽  
Factor Expression ◽  
Minimum Lethal Dose ◽  
Phosphate Sensor

Abstract Acinetobacter baumannii is a successful pathogen responsible for infections with high mortality rate. During the course of infection it can be found in microaerobic environments, which influences virulence factor expression. From a previous transcriptomic analysis of A. baumannii ATCC 17978 under microaerobiosis, we know the gene pstS is overexpressed under microaerobiosis. Here, we studied its role in A. baumannii virulence. pstS loss significantly decreased bacterial adherence and invasion into A549 cells and increased A549 cell viability. pstS loss also reduced motility and biofilm-forming ability of A. baumannii. In a peritoneal sepsis murine model, the minimum lethal dose required by A. baumannii ATCC 17978 ΔpstS was lower compared to the wild type (4.3 vs 3.2 log colony forming units/mL, respectively), and the bacterial burden in tissues and fluids was lower. Thus, the loss of the phosphate sensor PstS produced a decrease in A. baumannii pathogenesis, supporting its role as a virulence factor.

scholarly journals Characterization of the Role of the ToxR-Modulated Outer Membrane Porins OmpU and OmpT in Vibrio cholerae Virulence

2001 ◽  
Vol 183 (12) ◽  
pp. 3652-3662 ◽  
Author(s):  
Daniele Provenzano ◽  
Crystal M. Lauriano ◽  
Karl E. Klose
Keyword(s):  
Virulence Factor ◽  
Large Deletion ◽  
Wild Type ◽  
Coding Sequence ◽  
Rich Media ◽  
Outer Membrane Porins ◽  
Factor Expression

ABSTRACT ToxR, the transmembrane regulatory protein required for expression of virulence factors in the human diarrheal pathogen Vibrio cholerae, directly activates and represses the transcription of two outer membrane porins, OmpU and OmpT, respectively. In an attempt to dissect the role of the OmpU and OmpT porins in viability and virulence factor expression, in-frame chromosomal deletions were constructed in the coding sequences of ompU andompT of V. cholerae. Two separate deletions were introduced into ompU; the first (small) deletion, ΔompU1, removed the coding sequence for 84 internal amino acids (aa), while the second (large) deletion, ΔompU2, removed the coding sequence for the entire amino-terminal 274 aa. The ΔompU1 strain had a growth defect that could not be complemented by episomal expression of full-length ompU. In contrast, a strain with ΔompU2 displayed wild-type growth kinetics in rich media, suggesting that this is the true phenotype of a strain lacking OmpU and that the truncated OmpU protein, rather than the absence of OmpU, may be the cause for the ΔompU1phenotype. A large deletion removing the coding sequence for the entire N-terminal 273 aa of OmpT (ΔompT) was also constructed in wild-type as well as ΔtoxR and ΔompU2strains, and these strains displayed wild-type growth kinetics in rich media. However, the ΔompU2 strain was deficient for growth in deoxycholate compared to wild-type, ΔompT, and ΔompU2 ΔompT strains, reinforcing a positive role for the OmpU porin and a negative role for the OmpT porin in V. cholerae resistance to anionic detergents. The ΔompU2, ΔompT, and ΔompU2ΔompT strains exhibited wild-type levels of in vitro virulence factor expression and resistance to polymyxin B and serum and in vivo colonization levels similar to a wild-type strain in the infant mouse intestine. Our results demonstrate that (i) OmpU and OmpT are not essential proteins, as was previously thought; (ii) these porins contribute to V. cholerae resistance to anionic detergents; and (iii) OmpU and OmpT are not essential for virulence factor expression in vitro or intestinal colonization in vivo.

scholarly journals Pneumococcal Surface Protein C Contributes to Sepsis Caused by Streptococcus pneumoniae in Mice

2004 ◽  
Vol 72 (5) ◽  
pp. 3077-3080 ◽  
Author(s):  
Francesco Iannelli ◽  
Damiana Chiavolini ◽  
Susanna Ricci ◽  
Marco Rinaldo Oggioni ◽  
Gianni Pozzi
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein C ◽  
Lethal Dose ◽  
Surface Protein ◽  
Infection Model ◽  
Wild Type ◽  
Mutant Strains ◽  
Type 3

ABSTRACT The role of pneumococcal surface protein C (PspC; also called SpsA, CbpA, and Hic) in sepsis by Streptococcus pneumoniae was investigated in a murine infection model. The pspC gene was deleted in strains D39 (type 2) and A66 (type 3), and the mutants were tested by being injected intravenously into mice. The animals infected with the mutant strains showed a significant increase in survival, with the 50% lethal dose up to 250-fold higher than that for the wild type. Our findings indicate that PspC affords a decisive contribution to sepsis development.

scholarly journals Braun Lipoprotein (Lpp) Contributes to Virulence of Yersiniae: Potential Role of Lpp in Inducing Bubonic and Pneumonic Plague

2008 ◽  
Vol 76 (4) ◽  
pp. 1390-1409 ◽  
Author(s):  
Jian Sha ◽  
Stacy L. Agar ◽  
Wallace B. Baze ◽  
Juan P. Olano ◽  
Amin A. Fadl ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Potential Role ◽  
Lethal Dose ◽  
Wild Type ◽  
Pneumonic Plague ◽  
Essentially Normal ◽  
Serovar Typhimurium ◽  
Highly Virulent ◽  
Lethal Doses

ABSTRACT Yersinia pestis evolved from Y. pseudotuberculosis to become the causative agent of bubonic and pneumonic plague. We identified a homolog of the Salmonella enterica serovar Typhimurium lipoprotein (lpp) gene in Yersinia species and prepared lpp gene deletion mutants of Y. pseudotuberculosis YPIII, Y. pestis KIM/D27 (pigmentation locus minus), and Y. pestis CO92 with reduced virulence. Mice injected via the intraperitoneal route with 5 × 107 CFU of the Δlpp KIM/D27 mutant survived a month, even though this would have constituted a lethal dose for the parental KIM/D27 strain. Subsequently, these Δlpp KIM/D27-injected mice were solidly protected against an intranasally administered, highly virulent Y. pestis CO92 strain when it was given as five 50% lethal doses (LD50). In a parallel study with the pneumonic plague mouse model, after 72 h postinfection, the lungs of animals infected with wild-type (WT) Y. pestis CO92 and given a subinhibitory dose of levofloxacin had acute inflammation, edema, and masses of bacteria, while the lung tissue appeared essentially normal in mice inoculated with the Δlpp mutant of CO92 and given the same dose of levofloxacin. Importantly, while WT Y. pestis CO92 could be detected in the bloodstreams and spleens of infected mice at 72 h postinfection, the Δlpp mutant of CO92 could not be detected in those organs. Furthermore, the levels of cytokines/chemokines detected in the sera were significantly lower in animals infected with the Δlpp mutant than in those infected with WT CO92. Additionally, the Δlpp mutant was more rapidly killed by macrophages than was the WT CO92 strain. These data provided evidence that the Δlpp mutants of yersiniae were significantly attenuated and could be useful tools in the development of new vaccines.

scholarly journals Role of HtrA in the Virulence and Competence of Streptococcus pneumoniae

2004 ◽  
Vol 72 (6) ◽  
pp. 3584-3591 ◽  
Author(s):  
Yasser Musa Ibrahim ◽  
Alison R. Kerr ◽  
Jackie McCluskey ◽  
Tim J. Mitchell
Keyword(s):  
Oxidative Stress ◽  
Streptococcus Pneumoniae ◽  
Genetic Transformation ◽  
Mouse Models ◽  
High Temperatures ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Wild Type ◽  
Major Virulence Factor

ABSTRACT HtrA is a major virulence factor of Streptococcus pneumoniae (the pneumococcus). Deletion of the gene for HtrA from strain D39 of the pneumococcus completely abolished its virulence in mouse models of pneumonia and bacteremia, while the virulence of a second strain (TIGR4) was dramatically reduced. HtrA-negative mutants induced much less inflammation in the lungs during pneumonia than the wild type. HtrA is involved in the ability of the pneumococcus to grow at high temperatures, to resist oxidative stress, and to undergo genetic transformation. The expression and cellular location of several known virulence factors of the pneumococcus were not affected by the lack of HtrA.

scholarly journals Contribution of YjbIH to Virulence Factor Expression and Host Colonization inStaphylococcus aureus

2019 ◽  
Vol 87 (6) ◽  
Author(s):  
Crystal M. Austin ◽  
Siamak Garabaglu ◽  
Christina N. Krute ◽  
Miranda J. Ridder ◽  
Nichole A. Seawell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Virulence Factor ◽  
Type Strain ◽  
Wild Type Strain ◽  
Acute Infection ◽  
Minor Role ◽  
Wild Type ◽  
Truncated Hemoglobin ◽  
Factor Expression ◽  
And Oxidative Stress

ABSTRACTTo persist within the host and cause disease,Staphylococcus aureusrelies on its ability to precisely fine-tune virulence factor expression in response to rapidly changing environments. During an unbiased transposon mutant screen, we observed that disruption of a two-gene operon,yjbIH, resulted in decreased levels of pigmentation and aureolysin (Aur) activity relative to the wild-type strain. Further analyses revealed that YjbH, a predicted thioredoxin-like oxidoreductase, is predominantly responsible for the observedyjbIHmutant phenotypes, though a minor role exists for the putative truncated hemoglobin YjbI. These differences were due to significantly decreased expression ofcrtOPQMNandaur. Previous studies found that YjbH targets the disulfide- and oxidative stress-responsive regulator Spx for degradation by ClpXP. The absence ofyjbHoryjbIresulted in altered sensitivities to nitrosative and oxidative stress and iron deprivation. Additionally, aconitase activity was altered in theyjbHandyjbImutant strains. Decreased levels of pigmentation and aureolysin (Aur) activity in theyjbHmutant were found to be Spx dependent. Lastly, we used a murine sepsis model to determine the effect of theyjbIHdeletion on pathogenesis and found that the mutant was better able to colonize the kidneys and spleens during an acute infection than the wild-type strain. These studies identified changes in pigmentation and protease activity in response to YjbIH and are the first to have shown a role for these proteins during infection.

scholarly journals Activation of endothelial intrinsic NF-κB pathway impairs protein C anticoagulation mechanism and promotes coagulation in endotoxemic mice

Blood ◽  
2009 ◽  
Vol 114 (12) ◽  
pp. 2521-2529 ◽  
Author(s):  
Dongmei Song ◽  
Xiaobing Ye ◽  
Honglei Xu ◽  
Shu Fang Liu
Keyword(s):  
Transgenic Mice ◽  
Tissue Factor ◽  
Protein C ◽  
Nuclear Factor Κb ◽  
Tissue Factor Expression ◽  
Wild Type ◽  
Endothelial Protein C Receptor ◽  
Lps Challenge ◽  
Factor Expression

Abstract Although the role of systemic activation of the nuclear factor κB (NF-κB) pathway in septic coagulation has been well documented, little is known about the contribution of endothelial-specific NF-κB signaling in this pathologic process. Here, we used transgenic mice that conditionally overexpress a mutant I-κBα, an inhibitor of NF-κB, selectively on endothelium, and their wild-type littermates to define the role of endothelial-specific NF-κB in septic coagulation. In wild-type mice, lipopolysaccharide (LPS) challenge (5 mg/kg intraperitoneally) caused markedly increased plasma markers of coagulation, decreased plasma fibrinogen level, and widespread tissue fibrin deposition, which were abrogated by endothelial NF-κB blockade in transgenic mice. Endothelial NF-κB blockade inhibited tissue factor expression in endothelial cells, but not in leukocytes. Endothelial NF-κB blockade did not inhibit LPS-induced tissue factor expression in heart, kidney, and liver. Endothelial NF-κB blockade prevented LPS down-regulation of endothelial protein C receptor (EPCR) and thrombomodulin protein expressions, inhibited tissue tumor necrosis factor-α converting enzyme activity, reduced EPCR shedding, and restored plasma protein C level. Our data demonstrate that endothelial intrinsic NF-κB signaling plays a pivotal role in septic coagulation and suggests a link between endothelial-specific NF-κB activation and the impairment of the thrombomodulin-protein C-EPCR anticoagulation pathway.

scholarly journals ZapA, a Virulence Factor in a Rat Model of Proteus mirabilis-Induced Acute and Chronic Prostatitis

2008 ◽  
Vol 76 (11) ◽  
pp. 4859-4864 ◽  
Author(s):  
Van Phan ◽  
Robert Belas ◽  
Brendan F. Gilmore ◽  
Howard Ceri
Keyword(s):  
Virulence Factor ◽  
Proteus Mirabilis ◽  
Chronic Prostatitis ◽  
Bacterial Colonization ◽  
Wild Type ◽  
Chronic Bacterial Prostatitis ◽  
Important Virulence Factor ◽  
Specific Virulence

ABSTRACT Our knowledge of pathogenesis has benefited from a better understanding of the roles of specific virulence factors in disease. To determine the role of the virulence factor ZapA, a 54-kDa metalloproteinase of Proteus mirabilis, in prostatitis, rats were infected with either wild-type (WT) P. mirabilis or its isogenic ZapA− mutant KW360. The WT produced both acute and chronic prostatitis showing the typical histological progressions that are the hallmarks of these diseases. Infection with the ZapA− mutant, however, resulted in reduced levels of acute prostatitis, as determined from lower levels of tissue damage, bacterial colonization, and inflammation. Further, the ZapA− mutant failed to establish a chronic infection, in that bacteria were cleared from the prostate, inflammation was resolved, and tissue was seen to be healing. Clearance from the prostate was not the result of a reduced capacity of the ZapA− mutant to form biofilms in vitro. These finding clearly define ZapA as an important virulence factor in both acute and chronic bacterial prostatitis.

scholarly journals Properties of H7N7 influenza A virus strain SC35M lacking interferon antagonist NS1 in mice and chickens

2007 ◽  
Vol 88 (5) ◽  
pp. 1403-1409 ◽  
Author(s):  
Georg Kochs ◽  
Iris Koerner ◽  
Lena Thiel ◽  
Sonja Kothlow ◽  
Bernd Kaspers ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Virulence Factor ◽  
Influenza A ◽  
Severe Disease ◽  
A549 Cells ◽  
Type I ◽  
Upper Respiratory Tract ◽  
Structural Protein ◽  
Wild Type ◽  
Ns1 Gene

Non-structural protein NS1 of influenza A virus counteracts the host immune response by blocking the synthesis of type I interferon (IFN). As deletion of the complete NS1 gene has to date been reported only in the human H1N1 strain A/PR/8/34, it remained unclear whether NS1 is a non-essential virulence factor in other influenza A virus strains as well. In this report, the properties of NS1-deficient mutants derived from strain SC35M (H7N7) are described. A mutant of SC35M that completely lacks the NS1 gene was an excellent inducer of IFN in mammalian and avian cells in culture and, consequently, was able to multiply efficiently only in cell lines with defects in the type I IFN system. Virus mutants carrying C-terminally truncated versions of NS1 were less powerful inducers of IFN and were attenuated less strongly in human A549 cells. Although attenuated in wild-type mice, these mutants remained highly pathogenic for mice lacking the IFN-regulated antiviral factor Mx1. In contrast, the NS1-deficient SC35M mutant was completely non-pathogenic for wild-type mice, but remained pathogenic for mice lacking Mx1 and double-stranded RNA-activated protein kinase (PKR). Wild-type SC35M, but not the NS1-deficient mutant virus, was able to replicate in the upper respiratory tract of birds, but neither virus induced severe disease in adult chickens. Altogether, this study supports the view that NS1 represents a non-essential virulence factor of different influenza A viruses.

scholarly journals Protective potentials of a siderophore receptor against Acinetobacter baumannii infections

2019 ◽  
Vol 9 (4) ◽  
pp. 3987-3995
Keyword(s):  
Recombinant Protein ◽  
Acinetobacter Baumannii ◽  
Lethal Dose ◽  
A549 Cells ◽  
Cost Effective ◽  
Uptake System ◽  
Gene Encoding ◽  
Extensive Drug Resistance ◽  
Potential Vaccine ◽  
Experimental Findings

Acinetobacter baumannii causes nosocomial infections and high mortality rates in the world. Since antibiotic treatment is complicated by extensive drug resistance in A. baumannii strains, other approaches such as vaccination can be a cost-effective solution. Siderophore receptor related to cluster 1 of iron uptake system (WP_000413999) is expressed in early stages of A. baumannii’s infection under iron restricted conditions. In this study, structural characterization and immunogenicity of the target protein in a murine sepsis model were assessed. Structural properties of the siderophore receptor were determined by bioinformatics tools. The gene encoding the antigen was cloned in E. coli BL21(DE3) and was then expressed. The purified recombinant protein was administered to the mice subcutaneously for antibody production. The immunized mice were challenged with the A. baumannii at lethal dose via intraperitoneal injection. Blast results revealed more than 97% identity of the protein in 3472 strains of A. baumannii. This receptor is a TonB-dependent transporter with a barrel domain composed of 22 β-strands connected by external loops and periplasmic turns. Experimental findings showed that the recombinant protein had no toxicity effect on A549 cells. Moreover, the studied protein was able to induce a specific antibody response in the mice. Survival rate of the passive immunized mice was improved against sepsis caused by A. baumannii ATCC 19606 and ABI022 clinical isolate. The study indicated that this siderophore receptor can be considered for further analysis as a potential vaccine target against A. baumannii.

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