scholarly journals Glutamate Limitation, BvgAS Activation, and (p)ppGpp Regulate the Expression of the Bordetella pertussis Type 3 Secretion System

2015 ◽  
Vol 198 (2) ◽  
pp. 343-351 ◽  
Author(s):  
Tomoko Hanawa ◽  
Kazunari Kamachi ◽  
Hideo Yonezawa ◽  
Toshiyuki Fukutomi ◽  
Hayato Kawakami ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Protein Profile ◽  
Secretion System ◽  
Transcriptional Level ◽  
Content Type ◽  
Bacterial Physiology ◽  
Number Of Patients ◽  
Type 3 Secretion System ◽  
Type 3

ABSTRACTBordetella pertussisis a bacterium that is considered to be highly adapted to humans, and it has not been isolated from the environment. As this bacterium does not utilize sugars, the abundant supply of glutamate in Stainer Scholte (SS) medium enablesB. pertussisto grow efficiently in liquid culturein vitro, and as such, SS medium is a popular choice for laboratory experiments. However, the concentration of glutamate in thein vivoniche ofB. pertussisis quite low. We investigated the bacterial response to low concentrations of glutamate to elucidate bacterial physiology via the expression of the type 3 secretion system (T3SS), and we discuss its relationship to the Bvg mode in which the two-component regulator of pathogenesis (BvgAS) is activated. Glutamate limitation induced the expression of both the T3SS apparatus and effector genes at the transcriptional level. (p)ppGpp, a modulator of the stringent response, was necessary for maximum expression of the T3SS genes. These observations indicate that the expression of the T3SS is managed by nutrient starvation. In addition, the autoaggregation ability was high in the absence of glutamate and no autoaggregation was observed in glutamate-replete medium. Taken together, glutamate-limited conditions in Bvg+mode elicit the high expression of T3SS genes inB. pertussisand promotes its sessile form.IMPORTANCEBordetella pertussisis a highly contagious pathogen that causes respiratory infectious disease. In spite of the increasing use of vaccination, the number of patients with pertussis is increasing. The proteins producedin vivooften are different from the protein profile under laboratory conditions; therefore, the development of conditions reflecting the host environment is important to understand native bacterial behavior. In the present study, we examined the effect of glutamate limitation, as its concentrationin vivois much lower than that in the culture medium currently used forB. pertussisexperiments. As predicted, the T3SS was induced by glutamate limitation. These results are suggestive of the importance of regulation by nutrient conditions and in the pathogenicity ofB. pertussis.

scholarly journals Genomic Avenue to Avian Colisepticemia

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Sagi Huja ◽  
Yaara Oren ◽  
Eva Trost ◽  
Elzbieta Brzuszkiewicz ◽  
Dvora Biran ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Genetic Analysis ◽  
Virulence Factors ◽  
Iron Uptake ◽  
Secretion System ◽  
Economic Losses ◽  
Content Type ◽  
E Coli ◽  
Type 3 Secretion System ◽  
Type 3

ABSTRACTHere we present an extensive genomic and genetic analysis of Escherichia coli strains of serotype O78 that represent the major cause of avian colisepticemia, an invasive infection caused by avian pathogenicEscherichia coli(APEC) strains. It is associated with high mortality and morbidity, resulting in significant economic consequences for the poultry industry. To understand the genetic basis of the virulence of avian septicemic E. coli, we sequenced the entire genome of a clinical isolate of serotype O78—O78:H19 ST88 isolate 789 (O78-9)—and compared it with three publicly available APEC O78 sequences and one complete genome of APEC serotype O1 strain. Although there was a large variability in genome content between the APEC strains, several genes were conserved, which are potentially critical for colisepticemia. Some of these genes are present in multiple copies per genome or code for gene products with overlapping function, signifying their importance. A systematic deletion of each of these virulence-related genes identified three systems that are conserved in all septicemic strains examined and are critical for serum survival, a prerequisite for septicemia. These are the plasmid-encoded protein, the defective ETT2 (E. colitype 3 secretion system 2) type 3 secretion system ETT2sepsis, and iron uptake systems. Strain O78-9 is the only APEC O78 strain that also carried the regulon coding for yersiniabactin, the iron binding system of theYersiniahigh-pathogenicity island. Interestingly, this system is the only one that cannot be complemented by other iron uptake systems under iron limitation and in serum.IMPORTANCEAvian colisepticemia is a severe systemic disease of birds causing high morbidity and mortality and resulting in severe economic losses. The bacteria associated with avian colisepticemia are highly antibiotic resistant, making antibiotic treatment ineffective, and there is no effective vaccine due to the multitude of serotypes involved. To understand the disease and work out strategies to combat it, we performed an extensive genomic and genetic analysis of Escherichia coli strains of serotype O78, the major cause of the disease. We identified several potential virulence factors, conserved in all the colisepticemic strains examined, and determined their contribution to growth in serum, an absolute requirement for septicemia. These findings raise the possibility that specific vaccines or drugs can be developed against these critical virulence factors to help combat this economically important disease.

scholarly journals Regulation by ToxR-Like Proteins Converges onvttRBExpression To Control Type 3 Secretion System-Dependent Caco2-BBE Cytotoxicity in Vibrio cholerae

2016 ◽  
Vol 198 (11) ◽  
pp. 1675-1682 ◽  
Author(s):  
Kelly A. Miller ◽  
Madeline K. Sofia ◽  
Jacob W. A. Weaver ◽  
Christopher H. Seward ◽  
Michelle Dziejman
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Vibrio Cholerae ◽  
Secretion System ◽  
Content Type ◽  
Transcriptional Regulatory ◽  
Type 3 Secretion System ◽  
Type 3

ABSTRACTGenes carried on the type 3 secretion system (T3SS) pathogenicity island ofVibrio choleraenon-O1/non-O139 serogroup strain AM-19226 must be precisely regulated in order for bacteria to cause disease. Previously reported results showed that both T3SS function and the presence of bile are required to cause Caco2-BBE cell cytotoxicity during coculture with strain AM-19226. We therefore investigated additional parameters affectingin vitrocell death, including bacterial load and the role of three transmembrane transcriptional regulatory proteins, VttRA, VttRB, and ToxR. VttRAand VttRBare encoded on the horizontally acquired T3SS genomic island, whereas ToxR is encoded on the ancestral chromosome. While strains carrying deletions in any one of the three transcriptional regulatory genes are unable to cause eukaryotic cell death, the results of complementation studies point to a hierarchy of regulatory control that converges onvttRBexpression. The data suggest both that ToxR and VttRAact upstream of VttRBand that modifying the level of eithervttRAorvttRBexpression can strongly influence T3SS gene expression. We therefore propose a model whereby T3SS activity and, hence,in vitrocytotoxicity are ultimately regulated byvttRBexpression.IMPORTANCEIn contrast to O1 and O139 serogroupV. choleraestrains that cause cholera using two main virulence factors (toxin-coregulated pilus [TCP] and cholera toxin [CT]), O39 serogroup strain AM-19226 uses a type 3 secretion system as its principal virulence mechanism. Although the regulatory network governing TCP and CT expression is well understood, the factors influencing T3SS-associated virulence are not. Using anin vitromammalian cell model to investigate the role of three ToxR-like transmembrane transcriptional activators in causing T3SS-dependent cytotoxicity, we found that expression levels and a hierarchical organization were important for promoting T3SS gene expression. Furthermore, our results suggest that horizontally acquired, ToxR-like proteins act in concert with the ancestral ToxR protein to orchestrate T3SS-mediated pathogenicity.

scholarly journals Complete Genome Sequence of Pseudomonas aeruginosa CMC-115, a Clinical Strain from an Acute Ventilator-Associated Pneumonia Patient

2020 ◽  
Vol 9 (30) ◽  
Author(s):  
Adenike Adenikinju ◽  
Roderick V. Jensen ◽  
Thomas M. Kerkering ◽  
Dorothy C. Garner ◽  
Jayasimha Rao
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Complete Genome ◽  
Secretion System ◽  
Clinical Strain ◽  
Ventilator Associated Pneumonia ◽  
Circular Chromosome ◽  
Content Type ◽  
Pneumonia Patient ◽  
Type 3 Secretion System ◽  
Type 3

ABSTRACT We report the complete genome of clinical strain Pseudomonas aeruginosa CMC-115, which was isolated from an acute ventilator-associated pneumonia patient. Illumina sequencing reads were assembled using Geneious to yield a 6,375,262-bp circular chromosome that exhibited an unusual ferrichrome receptor in the pyoverdine synthesis locus and the absence of type 3 secretion system genes.

scholarly journals S-nitrosylation-mediated activation of a histidine kinase represses the type 3 secretion system and promotes virulence of an enteric pathogen

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dan Gu ◽  
Yibei Zhang ◽  
Qiyao Wang ◽  
Xiaohui Zhou
Keyword(s):  
Histidine Kinase ◽  
Vibrio Parahaemolyticus ◽  
Early Stage ◽  
Rabbit Model ◽  
Secretion System ◽  
Intestinal Colonization ◽  
Type 3 Secretion System ◽  
Proinflammatory Factor ◽  
Type 3

AbstractVibrio parahaemolyticus is the leading cause of seafood-borne diarrheal diseases. Experimental overproduction of a type 3 secretion system (T3SS1) in this pathogen leads to decreased intestinal colonization, which suggests that T3SS1 repression is required for maximal virulence. However, the mechanisms by which T3SS1 is repressed in vivo are unclear. Here, we show that host-derived nitrite modifies the activity of a bacterial histidine kinase and mediates T3SS1 repression. More specifically, nitrite activates histidine kinase sensor VbrK through S-nitrosylation on cysteine 86, which results in downregulation of the entire T3SS1 operon through repression of its positive regulator exsC. Replacement of cysteine 86 with a serine (VbrK C86S mutant) leads to increased expression of inflammatory cytokines in infected Caco-2 cells. In an infant rabbit model of infection, the VbrK C86S mutant induces a stronger inflammatory response at the early stage of infection, and displays reduced intestinal colonization and virulence at the later stage of infection, in comparison with the parent strain. Our results indicate that the pathogen V. parahaemolyticus perceives nitrite as a host-derived signal and responds by downregulating a proinflammatory factor (T3SS1), thus enhancing intestinal colonization and virulence.

scholarly journals Response of Pseudomonas aeruginosa to the Innate Immune System-Derived Oxidants Hypochlorous Acid and Hypothiocyanous Acid

2020 ◽  
Vol 203 (2) ◽  
pp. e00300-20
Author(s):  
Katie V. Farrant ◽  
Livia Spiga ◽  
Jane C. Davies ◽  
Huw D. Williams
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Immune System ◽  
Hypochlorous Acid ◽  
Secretion System ◽  
Content Type ◽  
Type 3 Secretion System ◽  
Lung Infections ◽  
Type 3

ABSTRACTPseudomonas aeruginosa is a significant nosocomial pathogen and is associated with lung infections in cystic fibrosis (CF). Once established, P. aeruginosa infections persist and are rarely eradicated despite host immune cells producing antimicrobial oxidants, including hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). There is limited knowledge as to how P. aeruginosa senses, responds to, and protects itself against HOCl and HOSCN and the contribution of such responses to its success as a CF pathogen. To investigate the P. aeruginosa response to these oxidants, we screened 707 transposon mutants, with mutations in regulatory genes, for altered growth following HOCl exposure. We identified regulators of antibiotic resistance, methionine biosynthesis, catabolite repression, and PA14_07340, the homologue of the Escherichia coli HOCl-sensor RclR (30% identical), which are required for protection against HOCl. We have shown that RclR (PA14_07340) protects specifically against HOCl and HOSCN stress and responds to both oxidants by upregulating the expression of a putative peroxiredoxin, rclX (PA14_07355). Transcriptional analysis revealed that while there was specificity in the response to HOCl (231 genes upregulated) and HOSCN (105 genes upregulated), there was considerable overlap, with 74 genes upregulated by both oxidants. These included genes encoding the type 3 secretion system, sulfur and taurine transport, and the MexEF-OprN efflux pump. RclR coordinates part of the response to both oxidants, including upregulation of pyocyanin biosynthesis genes, and, in the presence of HOSCN, downregulation of chaperone genes. These data indicate that the P. aeruginosa response to HOCl and HOSCN is multifaceted, with RclR playing an essential role.IMPORTANCE The bacterial pathogen Pseudomonas aeruginosa causes devastating infections in immunocompromised hosts, including chronic lung infections in cystic fibrosis patients. To combat infection, the host’s immune system produces the antimicrobial oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). Little is known about how P. aeruginosa responds to and survives attack from these oxidants. To address this, we carried out two approaches: a mutant screen and transcriptional study. We identified the P. aeruginosa transcriptional regulator, RclR, which responds specifically to HOCl and HOSCN stress and is essential for protection against both oxidants. We uncovered a link between the P. aeruginosa transcriptional response to these oxidants and physiological processes associated with pathogenicity, including antibiotic resistance and the type 3 secretion system.

scholarly journals Laboratory Adaptation of Bordetella pertussis Is Associated with the Loss of Type Three Secretion System Functionality

2011 ◽  
Vol 79 (9) ◽  
pp. 3677-3682 ◽  
Author(s):  
M. E. Gaillard ◽  
D. Bottero ◽  
C. E. Castuma ◽  
L. A. Basile ◽  
D. Hozbor
Keyword(s):  
Bordetella Pertussis ◽  
Growth Conditions ◽  
Secretion System ◽  
Clinical Isolates ◽  
Content Type ◽  
Type Three Secretion System ◽  
Associated Proteins ◽  
Type Three Secretion

ABSTRACTAlthoughBordetella pertussiscontains and transcribes loci encoding type III secretion system (TTSS) homologues, expression of TTSS-associated proteins has been reported only for non-laboratory-adapted Irish clinical isolates. Here we confirm such a result for clinical isolates obtained from patients treated in Argentinean hospitals. Moreover, we demonstrate that the expression of TTSS-associated proteins is independent both of the year in which the isolate was obtained and of the types of polymorphic alleles for other virulence factors but is dependent on environmental growth conditions. Interestingly, we observed that TTSS-associated protein expression is lost after successivein vitropassages but becomes operative again when bacteria come into contact with the host. Thisin vivoactivation of TTSS expression was observed not only for clinical isolates previously adapted to the laboratory after successivein vitropassages but also for vaccine strains that did not express the systemin vitro. The reversibility of TTSS expression, demonstrated by its switching off-on when the bacterium comes into contact with the host, appears to be an adaptive response of this pathogen.

scholarly journals A Primed Subpopulation of Bacteria Enables Rapid Expression of the Type 3 Secretion System in Pseudomonas aeruginosa

mBio ◽  
2021 ◽  
Author(s):  
Christina K. Lin ◽  
Daniel S. W. Lee ◽  
Saria McKeithen-Mead ◽  
Thierry Emonet ◽  
Barbara Kazmierczak
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Secretion System ◽  
Innate Immune ◽  
Secretion Systems ◽  
Content Type ◽  
Acute Infections ◽  
A Cell ◽  
Type 3 Secretion System ◽  
Type 3 ◽  
Specific Virulence

The expression of specific virulence traits is strongly associated with Pseudomonas aeruginosa ’s success in establishing acute infections but is thought to carry a cost for bacteria. Producing multiprotein secretion systems or motility organelles is metabolically expensive and can target a cell for recognition by innate immune system receptors that recognize structural components of the type 3 secretion system (T3SS) or flagellum.

scholarly journals The HrpG/HrpX Regulon of Xanthomonads—An Insight to the Complexity of Regulation of Virulence Traits in Phytopathogenic Bacteria

2021 ◽  
Vol 9 (1) ◽  
pp. 187
Author(s):  
Doron Teper ◽  
Sheo Shankar Pandey ◽  
Nian Wang
Keyword(s):  
Regulatory Network ◽  
Regulatory Networks ◽  
Focal Point ◽  
Genetic Regulation ◽  
Transcriptional Regulators ◽  
Secretion System ◽  
In Planta ◽  
Type 3 Secretion System ◽  
Type 3 ◽  
Made In

Bacteria of the genus Xanthomonas cause a wide variety of economically important diseases in most crops. The virulence of the majority of Xanthomonas spp. is dependent on secretion and translocation of effectors by the type 3 secretion system (T3SS) that is controlled by two master transcriptional regulators HrpG and HrpX. Since their discovery in the 1990s, the two regulators were the focal point of many studies aiming to decipher the regulatory network that controls pathogenicity in Xanthomonas bacteria. HrpG controls the expression of HrpX, which subsequently controls the expression of T3SS apparatus genes and effectors. The HrpG/HrpX regulon is activated in planta and subjected to tight metabolic and genetic regulation. In this review, we cover the advances made in understanding the regulatory networks that control and are controlled by the HrpG/HrpX regulon and their conservation between different Xanthomonas spp.

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