scholarly journals Deleting qseC downregulates virulence and promotes cross-protection in Pasteurella multocida

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Yang Yang ◽  
Pei Hu ◽  
Lixu Gao ◽  
Xiang Yuan ◽  
Philip R. Hardwidge ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Iron Uptake ◽  
Pasteurella Multocida ◽  
Bacterial Virulence ◽  
Sequencing Analysis ◽  
Immune Protection ◽  
Global Regulator ◽  
Two Component System ◽  
Capsule Production ◽  
Histidine Sensor Kinase

AbstractQseC, a histidine sensor kinase of the QseBC two-component system, acts as a global regulator of bacterial stress resistance, biofilm formation, and virulence. The function of QseC in some bacteria is well understood, but not in Pasteurella multocida. We found that deleting qseC in P. multocida serotype A:L3 significantly down-regulated bacterial virulence. The mutant had significantly reduced capsule production but increased resistance to oxidative stress and osmotic pressure. Deleting qseC led to a significant increase in qseB expression. Transcriptome sequencing analysis showed that 1245 genes were regulated by qseC, primarily those genes involved in capsule and LPS biosynthesis and export, biofilm formation, and iron uptake/utilization, as well as several immuno-protection related genes including ompA, ptfA, plpB, vacJ, and sodA. In addition to presenting strong immune protection against P. multocida serotypes A:L1 and A:L3 infection, live ΔqseC also exhibited protection against P. multocida serotype B:L2 and serotype F:L3 infection in a mouse model. The results indicate that QseC regulates capsular production and virulence in P. multocida. Furthermore, the qseC mutant can be used as an attenuated vaccine against P. multocida strains of multiple serotypes.

scholarly journals RND Efflux Systems Contribute to Resistance and Virulence of Aliarcobacter butzleri

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 823
Author(s):  
Cristiana Mateus ◽  
Ana Rita Nunes ◽  
Mónica Oleastro ◽  
Fernanda Domingues ◽  
Susana Ferreira
Keyword(s):  
Oxidative Stress ◽  
Human Serum ◽  
Ethidium Bromide ◽  
Biofilm Formation ◽  
Bacterial Resistance ◽  
Efflux Pumps ◽  
Bacterial Virulence ◽  
Relative Fitness ◽  
Mutant Strains

Aliarcobacter butzleri is an emergent enteropathogen that can be found in a range of environments. This bacterium presents a vast repertoire of efflux pumps, such as the ones belonging to the resistance nodulation cell division family, which may be associated with bacterial resistance, as well as virulence. Thus, this work aimed to evaluate the contribution of three RND efflux systems, AreABC, AreDEF and AreGHI, in the resistance and virulence of A. butzleri. Mutant strains were constructed by inactivation of the gene that encodes the inner membrane protein of these systems. The bacterial resistance profile of parental and mutant strains to several antimicrobials was assessed, as was the intracellular accumulation of the ethidium bromide dye. Regarding bacterial virulence, the role of these three efflux pumps on growth, strain fitness, motility, biofilm formation ability, survival in adverse conditions (oxidative stress and bile salts) and human serum and in vitro adhesion and invasion to Caco-2 cells was evaluated. We observed that the mutants from the three efflux pumps were more susceptible to several classes of antimicrobials than the parental strain and presented an increase in the accumulation of ethidium bromide, indicating a potential role of the efflux pumps in the extrusion of antimicrobials. The mutant strains had no bacterial growth defects; nonetheless, they presented a reduction in relative fitness. For the three mutants, an increase in the susceptibility to oxidative stress was observed, while only the mutant for AreGHI efflux pump showed a relevant role in bile stress survival. All the mutant strains showed an impairment in biofilm formation ability, were more susceptible to human serum and were less adherent to intestinal epithelial cells. Overall, the results support the contribution of the efflux pumps AreABC, AreDEF and AreGHI of A. butzleri to antimicrobial resistance, as well as to bacterial virulence.

scholarly journals Transcriptome Analysis Reveals the Genes Involved in Bifidobacterium Longum FGSZY16M3 Biofilm Formation

2021 ◽  
Vol 9 (2) ◽  
pp. 385 ◽  
Author(s):  
Zongmin Liu ◽  
Lingzhi Li ◽  
Qianwen Wang ◽  
Faizan Ahmed Sadiq ◽  
Yuankun Lee ◽  
...  
Keyword(s):  
Network Analysis ◽  
Biofilm Formation ◽  
Extracellular Polymeric Substances ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Bifidobacterium Longum ◽  
Regulation Of Gene Expression ◽  
Interaction Network ◽  
Structural Development ◽  
Sequencing Analysis

Biofilm formation has evolved as an adaptive strategy for bacteria to cope with harsh environmental conditions. Currently, little is known about the molecular mechanisms of biofilm formation in bifidobacteria. A time series transcriptome sequencing analysis of both biofilm and planktonic cells of Bifidobacterium longum FGSZY16M3 was performed to identify candidate genes involved in biofilm formation. Protein–protein interaction network analysis of 1296 differentially expressed genes during biofilm formation yielded 15 clusters of highly interconnected nodes, indicating that genes related to the SOS response (dnaK, groS, guaB, ruvA, recA, radA, recN, recF, pstA, and sufD) associated with the early stage of biofilm formation. Genes involved in extracellular polymeric substances were upregulated (epsH, epsK, efp, frr, pheT, rfbA, rfbJ, rfbP, rpmF, secY and yidC) in the stage of biofilm maturation. To further investigate the genes related to biofilm formation, weighted gene co-expression network analysis (WGCNA) was performed with 2032 transcript genes, leading to the identification of nine WGCNA modules and 133 genes associated with response to stress, regulation of gene expression, quorum sensing, and two-component system. These results indicate that biofilm formation in B. longum is a multifactorial process, involving stress response, structural development, and regulatory processes.

scholarly journals Nutritional Regulation of the Sae Two-Component System by CodY inStaphylococcus aureus

2018 ◽  
Vol 200 (8) ◽  
Author(s):  
Kevin D. Mlynek ◽  
William E. Sause ◽  
Derek E. Moormeier ◽  
Marat R. Sadykov ◽  
Kurt R. Hill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virulence Factors ◽  
Virulence Gene ◽  
Nutrient Depletion ◽  
Global Regulator ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Two Component

ABSTRACTStaphylococcus aureussubverts innate defenses during infection in part by killing host immune cells to exacerbate disease. This human pathogen intercepts host cues and activates a transcriptional response via theS. aureusexoprotein expression (SaeR/SaeS [SaeR/S]) two-component system to secrete virulence factors critical for pathogenesis. We recently showed that the transcriptional repressor CodY adjusts nuclease (nuc) gene expression via SaeR/S, but the mechanism remained unknown. Here, we identified two CodY binding motifs upstream of thesaeP1 promoter, which suggested direct regulation by this global regulator. We show that CodY shares a binding site with the positive activator SaeR and that alleviating direct CodY repression at this site is sufficient to abrogate stochastic expression, suggesting that CodY repressessaeexpression by blocking SaeR binding. Epistasis experiments support a model that CodY also controlssaeindirectly through Agr and Rot-mediated repression of thesaeP1 promoter. We also demonstrate that CodY repression ofsaerestrains production of secreted cytotoxins that kill human neutrophils. We conclude that CodY plays a previously unrecognized role in controlling virulence gene expression via SaeR/S and suggest a mechanism by which CodY acts as a master regulator of pathogenesis by tying nutrient availability to virulence gene expression.IMPORTANCEBacterial mechanisms that mediate the switch from a commensal to pathogenic lifestyle are among the biggest unanswered questions in infectious disease research. Since the expression of most virulence genes is often correlated with nutrient depletion, this implies that virulence is a response to the lack of nourishment in host tissues and that pathogens likeS. aureusproduce virulence factors in order to gain access to nutrients in the host. Here, we show that specific nutrient depletion signals appear to be funneled to the SaeR/S system through the global regulator CodY. Our findings reveal a strategy by whichS. aureusdelays the production of immune evasion and immune-cell-killing proteins until key nutrients are depleted.

scholarly journals Investigation of Iron uptake and virulence gene factors (fur, tonB, exbD, exbB, hgbA, hgbB1, hgbB2 and tbpA) among isolates of Pasteurella multocida from Iran

2019 ◽  
Author(s):  
Motahare Feizabadi Farahani ◽  
Majid Esmaelizad ◽  
Ahmad Reza Jabbari
Keyword(s):  
Virulence Factors ◽  
Iron Uptake ◽  
Pasteurella Multocida ◽  
Iron Acquisition ◽  
Virulence Gene ◽  
Basic Information ◽  
Iron Supply ◽  
Wide Range ◽  
Pcr Method ◽  
First Time

Background and Objectives: Iron is an essential compound in metabolic pathway of wide range of organisms. Because of limited free iron supply in mammalian and avian hosts, bacteria have applied various ways to acquire iron. Materials and Methods: In this study, the frequency of 8 iron acquisition factors was examined among 63 avian and ovine Pasteurella multocida field isolates and their vaccine strains using PCR method. Results: Five candidate genes (fur, tonB, exbD, exbB and hgbA) were identified among all isolates. For the first time, 2 loci (hgbB1 and hgbB2) of the hgbB gene were identified, which were previously reported as 1 gene. Also, it was found that 5 ovine and 1 avian isolates possessed all the virulence factors, which could also be considered for evaluating the frequency of other virulence factors. Conclusion: More studies need to be conducted on the frequency of all other virulence factors among these isolates, which can provide basic information for improvement or substitution of current vaccinal strains. Overall, as the new designed sets of primers showed more potential in detecting the corresponded genes, researchers can consider them in further studies.

scholarly journals Effect of Overexpressing rsmA from Pseudomonas aeruginosa on Virulence of Select Phytotoxin-Producing Strains of P. syringae

2012 ◽  
Vol 102 (6) ◽  
pp. 575-587 ◽  
Author(s):  
Hye Suk Kong ◽  
Daniel P. Roberts ◽  
Cheryl D. Patterson ◽  
Sarah A. Kuehne ◽  
Stephan Heeb ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Signal Transduction Pathway ◽  
Leaf Tissue ◽  
Transcriptional Regulators ◽  
Growth Conditions ◽  
Transduction Pathway ◽  
Two Component System ◽  
Empty Vector ◽  
Alginate Production ◽  
Two Component

The GacS/GacA two-component system functions mechanistically in conjunction with global post-transcriptional regulators of the RsmA family to allow pseudomonads and other bacteria to adapt to changing environmental stimuli. Analysis of this Gac/Rsm signal transduction pathway in phytotoxin-producing pathovars of Pseudmonas syringae is incomplete, particularly with regard to rsmA. Our approach in studying it was to overexpress rsmA in P. syringae strains through introduction of pSK61, a plasmid constitutively expressing this gene. Disease and colonization of plant leaf tissue were consistently diminished in all P. syringae strains tested (pv. phaseolicola NPS3121, pv. syringae B728a, and BR2R) when harboring pSK61 relative to these isolates harboring the empty vector pME6031. Phaseolotoxin, syringomycin, and tabtoxin were not produced in any of these strains when transformed with pSK61. Production of protease and pyoverdin as well as swarming were also diminished in all of these strains when harboring pSK61. In contrast, alginate production, biofilm formation, and the hypersensitive response were diminished in some but not all of these isolates under the same growth conditions. These results indicate that rsmA is consistently important in the overarching phenotypes disease and endophtyic colonization but that its role varies with pathovar in certain underpinning phenotypes in the phytotoxin-producing strains of P. syringae.

scholarly journals Erratum for Petruzzi et al., “Capsular Polysaccharide Interferes with Biofilm Formation by Pasteurella multocida Serogroup A”

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Briana Petruzzi ◽  
Robert E. Briggs ◽  
Fred M. Tatum ◽  
W. Edward Swords ◽  
Cristina De Castro ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Pasteurella Multocida ◽  
Capsular Polysaccharide

scholarly journals Reassessing the Role of the Type II MqsRA Toxin-Antitoxin System in Stress Response and Biofilm Formation: mqsA Is Transcriptionally Uncoupled from mqsR

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Nathan Fraikin ◽  
Clothilde J. Rousseau ◽  
Nathalie Goeders ◽  
Laurence Van Melderen
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Biofilm Formation ◽  
Bile Salts ◽  
Regulatory Networks ◽  
Constitutive Expression ◽  
Toxin Gene ◽  
Global Regulator ◽  
Bacterial Physiology

ABSTRACT Toxin-antitoxin (TA) systems are broadly distributed modules whose biological roles remain mostly unknown. The mqsRA system is a noncanonical TA system in which the toxin and antitoxins genes are organized in operon but with the particularity that the toxin gene precedes that of the antitoxin. This system was shown to regulate global processes such as resistance to bile salts, motility, and biofilm formation. In addition, the MqsA antitoxin was shown to be a master regulator that represses the transcription of the csgD, cspD, and rpoS global regulator genes, thereby displaying a pleiotropic regulatory role. Here, we identified two promoters located in the toxin sequence driving the constitutive expression of mqsA, allowing thereby excess production of the MqsA antitoxin compared to the MqsR toxin. Our results show that both antitoxin-specific and operon promoters are not regulated by stresses such as amino acid starvation, oxidative shock, or bile salts. Moreover, we show that the MqsA antitoxin is not a global regulator as suggested, since the expression of csgD, cspD and rpoS is similar in wild-type and ΔmqsRA mutant strains. Moreover, these two strains behave similarly in terms of biofilm formation and sensitivity to oxidative stress or bile salts. IMPORTANCE There is growing controversy regarding the role of chromosomal toxin-antitoxin systems in bacterial physiology. mqsRA is a peculiar toxin-antitoxin system, as the gene encoding the toxin precedes that of the antitoxin. This system was previously shown to play a role in stress response and biofilm formation. In this work, we identified two promoters specifically driving the constitutive expression of the antitoxin, thereby decoupling the expression of antitoxin from the toxin. We also showed that mqsRA contributes neither to the regulation of biofilm formation nor to the sensitivity to oxidative stress and bile salts. Finally, we were unable to confirm that the MqsA antitoxin is a global regulator. Altogether, our data are ruling out the involvement of the mqsRA system in Escherichia coli regulatory networks.

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