scholarly journals Analysis of the Polysaccharide Capsule of the Systemic Pathogen Streptococcus iniae and Its Implications in Virulence

2006 ◽  
Vol 75 (3) ◽  
pp. 1255-1264 ◽  
Author(s):  
Beth A. Lowe ◽  
Jesse D. Miller ◽  
Melody N. Neely
Keyword(s):  
Capsular Polysaccharide ◽  
Virulent Strain ◽  
Systemic Disease ◽  
Systemic Infection ◽  
Streptococcus Iniae ◽  
Capsule Production ◽  
Commensal Strain ◽  
Capsule Locus ◽  
In The Beginning ◽  
Severe Systemic Disease

ABSTRACT Systemic pathogens have developed numerous strategies for evading the defenses of the host, permitting dissemination and multiplication in various tissues. One means of survival in the host, particularly in the bloodstream, has been attributed to the ability to avoid phagocytosis via capsular polysaccharide. To further define the virulence capacity of Streptococcus iniae, a zoonotic pathogen with the ability to cause severe systemic disease in both fish and humans, we performed an analysis of the capsule locus. The initial analysis included cloning and sequencing of the capsule synthesis operon, which revealed an approximately 21-kb region that is highly homologous to capsule operons of other streptococci. A genetic comparison of S. iniae virulent strain 9117 and commensal strain 9066 revealed that the commensal strain does not have the central region of the capsule operon composed of several important capsule synthesis genes. Four 9117 insertion or deletion mutants with mutations in the beginning, middle, or end of the capsule locus were analyzed to determine their capsule production and virulence. Virulence profiles were analyzed for each mutant using three separate criteria, which demonstrated the attenuation of each mutant in several tissue environments. These analyses also provided insight into the different responses of the host to each mutant strain compared to a wild-type infection. Our results demonstrate that capsule is not required for all host environments, while excess capsule is also not optimal, suggesting that for an “ideal” systemic infection, capsule production is most likely regulated while the bacterium is in different environments of the host.

scholarly journals Key Role of Capsular Polysaccharide in the Induction of Systemic Infection and Abortion by Hypervirulent Campylobacter jejuni

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Orhan Sahin ◽  
Samantha A. Terhorst ◽  
Eric R. Burrough ◽  
Zhangqi Shen ◽  
Zuowei Wu ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Campylobacter Jejuni ◽  
Capsular Polysaccharide ◽  
Systemic Infection ◽  
The United States ◽  
Content Type ◽  
Model Following ◽  
Capsule Production ◽  
Guinea Pig Model

ABSTRACT Campylobacter jejuni is a zoonotic pathogen, and a hypervirulent clone, named clone SA, has recently emerged as the predominant cause of ovine abortion in the United States. To induce abortion, orally ingested Campylobacter must translocate across the intestinal epithelium, spread systemically in the circulation, and reach the fetoplacental tissue. Bacterial factors involved in these steps are not well understood. C. jejuni is known to produce capsular polysaccharide (CPS), but the specific role that CPS plays in systemic infection and particularly abortion in animals remains to be determined. In this study, we evaluated the role of CPS in bacteremia using a mouse model and in abortion using a pregnant guinea pig model following oral challenge. Compared with C. jejuni NCTC 11168 and 81-176, a clone SA isolate (IA3902) resulted in significantly higher bacterial counts and a significantly longer duration of bacteremia in mice. The loss of capsule production via gene-specific mutagenesis in IA3902 led to the complete abolishment of bacteremia in mice and abortion in pregnant guinea pigs, while complementation of capsule expression almost fully restored these phenotypes. The capsule mutant strain was also impaired for survival in guinea pig sera and sheep blood. Sequence-based analyses revealed that clone SA possesses a unique CPS locus with a mosaic structure, which has been stably maintained in all clone SA isolates derived from various hosts and times. These findings establish CPS as a key virulence factor for the induction of systemic infection and abortion in pregnant animals and provide a viable candidate for the development of vaccines against hypervirulent C. jejuni.

scholarly journals Prevention and Cure of Systemic Escherichia coli K1 Infection by Modification of the Bacterial Phenotype

2004 ◽  
Vol 48 (5) ◽  
pp. 1503-1508 ◽  
Author(s):  
Naseem Mushtaq ◽  
Maria B. Redpath ◽  
J. Paul Luzio ◽  
Peter W. Taylor
Keyword(s):  
Escherichia Coli ◽  
Capsular Polysaccharide ◽  
Virulent Strain ◽  
Polysialic Acid ◽  
Intraperitoneal Administration ◽  
Systemic Infection ◽  
E Coli ◽  
Inhibition Of Growth ◽  
Old Rats ◽  
Prevention And Cure

ABSTRACT Escherichia coli is a common cause of meningitis and sepsis in the newborn infant, and the large majority of isolates from these infections produce a polysialic acid (PSA) capsular polysaccharide, the K1 antigen, that protects the bacterial cell from immune attack. We determined whether a capsule-depolymerizing enzyme, by removing this protective barrier, could alter the outcome of systemic infection in an animal model. Bacteriophage-derived endosialidase E (endoE) selectively degrades the PSA capsule on the surface of E. coli K1 strains. Intraperitoneal administration of small quantities of recombinant endoE (20 μg) to 3-day-old rats, colonized with a virulent strain of K1, prevented bacteremia and death from systemic infection. The enzyme had no effect on the viability of E. coli strains but sensitized strains expressing PSA to killing by the complement system. This study demonstrates the potential therapeutic efficacy of agents that cure infections by modification of the bacterial phenotype rather than by killing or inhibition of growth of the pathogen.

scholarly journals Transformation of nonencapsulated Streptococcus pneumoniae during systemic infection

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jessica L. Bradshaw ◽  
Iftekhar M. Rafiqullah ◽  
D. Ashley Robinson ◽  
Larry S. McDaniel
Keyword(s):  
Streptococcus Pneumoniae ◽  
Systemic Infection ◽  
Dna Uptake ◽  
Pathogenic Potential ◽  
Bacterial Surface ◽  
Capsule Production ◽  
Virulent Strains ◽  
Capsule Locus ◽  
Ear Infections ◽  
Complement Deposition

Abstract Streptococcus pneumoniae (pneumococcus) is a principal cause of bacterial middle ear infections, pneumonia, and meningitis. Capsule-targeted pneumococcal vaccines have likely contributed to increased carriage of nonencapsulated S. pneumoniae (NESp). Some NESp lineages are associated with highly efficient DNA uptake and transformation frequencies. However, NESp strains lack capsule that may increase disease severity. We tested the hypothesis that NESp could acquire capsule during systemic infection and transform into more virulent pneumococci. We reveal that NESp strains MNZ67 and MNZ41 are highly transformable and resistant to multiple antibiotics. Natural transformation of NESp when co-administered with heat-killed encapsulated strain WU2 in a murine model of systemic infection resulted in encapsulation of NESp and increased virulence during bacteremia. Functional capsule production increased the pathogenic potential of MNZ67 by significantly decreasing complement deposition on the bacterial surface. However, capsule acquisition did not further decrease complement deposition on the relatively highly pathogenic strain MNZ41. Whole genome sequencing of select transformants demonstrated that recombination of up to 56.7 kbp length occurred at the capsule locus, along with additional recombination occurring at distal sites harboring virulence-associated genes. These findings indicate NESp can compensate for lack of capsule production and rapidly evolve into more virulent strains.

scholarly journals Requirement for Capsule in Colonization byStreptococcus pneumoniae

2001 ◽  
Vol 69 (6) ◽  
pp. 3755-3761 ◽  
Author(s):  
Ashalla D. Magee ◽  
Janet Yother
Keyword(s):  
Capsular Polysaccharide ◽  
Invasive Disease ◽  
Intravenous Route ◽  
Survival Times ◽  
Nasopharyngeal Colonization ◽  
Capsule Production ◽  
Capsule Locus ◽  
Type 3 ◽  
Derivatives Of

ABSTRACT Nasopharyngeal colonization is a necessary first step in the pathogenesis of Streptococcus pneumoniae. Using isolates containing defined mutations in the S. pneumoniaecapsule locus, we found that expression of the capsular polysaccharide is essential for colonization by the type 2 strain D39 and the type 3 strains A66 and WU2. Nonencapsulated derivatives of each of these strains were unable to colonize BALB/cByJ mice. Similarly, type 3 mutants that produced <6% of the parental amounts of capsule could not colonize. Capsule production equivalent to that of the parent strain was not required for efficient colonization, however, as type 3 mutants producing approximately 20% of the parental amounts of capsule colonized as effectively as the parent. This 80% reduction in capsule level had only a minimal effect on intraperitoneal virulence but caused a significant reduction in virulence via the intravenous route. In the X-linked immunodeficient CBA/N mouse, the type 3 mutant producing ∼20% of the parental amount of capsule (AM188) was diminished in its ability to cause invasive disease and death following intranasal inoculation. Following intravenous or intraperitoneal challenge, however, only extended survival times were observed. Our results demonstrate an additional role for capsule in the pathogenesis ofS. pneumoniae and show that isolates producing reduced levels of capsule can remain highly virulent.

scholarly journals Capsule Biosynthesis and Basic Metabolism inStreptococcus pneumoniae Are Linked through the Cellular Phosphoglucomutase

2000 ◽  
Vol 182 (7) ◽  
pp. 1854-1863 ◽  
Author(s):  
Gail G. Hardy ◽  
Melissa J. Caimano ◽  
Janet Yother
Keyword(s):  
Capsular Polysaccharide ◽  
Spontaneous Mutation ◽  
Growth Defects ◽  
Capsule Production ◽  
Insertional Inactivation ◽  
Genes Encoding ◽  
Capsule Locus ◽  
Parental Level ◽  
Type 3 ◽  
Insertion Mutants

ABSTRACT Synthesis of the type 3 capsular polysaccharide ofStreptococcus pneumoniae requires UDP-glucose (UDP-Glc) and UDP-glucuronic acid (UDP-GlcUA) for production of the [3)-β-d-GlcUA-(1→4)-β-d-Glc-(1→] n polymer. The generation of UDP-Glc proceeds by conversion of Glc-6-P to Glc-1-P to UDP-Glc and is mediated by a phosphoglucomutase (PGM) and a Glc-1-P uridylyltransferase, respectively. Genes encoding both a Glc-1-P uridylyltransferase (cps3U) and a PGM homologue (cps3M) are present in the type 3 capsule locus, but these genes are not essential for capsule production. In this study, we characterized a mutant that produces fourfold less capsule than the type 3 parent. The spontaneous mutation resulting in this phenotype was not contained in the type 3 capsule locus but was instead located in a distant gene (pgm) encoding a second PGM homologue. The function of this gene product as a PGM was demonstrated through enzymatic and complementation studies. Insertional inactivation ofpgm reduced capsule production to less than 10% of the parental level. The loss of PGM activity in the insertion mutants also caused growth defects and a strong selection for isolates containing second-site suppressor mutations. These results demonstrate that most of the PGM activity required for type 3 capsule biosynthesis is derived from the cellular PGM.

scholarly journals Positive Correlation between Tyrosine Phosphorylation of CpsD and Capsular Polysaccharide Production in Streptococcus pneumoniae

2003 ◽  
Vol 185 (20) ◽  
pp. 6057-6066 ◽  
Author(s):  
Matthew H. Bender ◽  
Robert T. Cartee ◽  
Janet Yother
Keyword(s):  
Cell Wall ◽  
Streptococcus Pneumoniae ◽  
Tyrosine Phosphorylation ◽  
Capsular Polysaccharide ◽  
Kinase Inhibitor ◽  
Tyrosine Phosphatase ◽  
Regulatory System ◽  
Capsule Production ◽  
Capsule Locus ◽  
Ladder Pattern

ABSTRACT CpsA, CpsB, CpsC, and CpsD are part of a tyrosine phosphorylation regulatory system involved in modulation of capsule synthesis in Streptococcus pneumoniae and many other gram-positive and gram-negative bacteria. Using an immunoblotting technique, we observed distinct laddering patterns of S. pneumoniae capsular polysaccharides of various serotypes and found that transfer of the polymer from the membrane to the cell wall was independent of size. Deletion of cps2A, cps2B, cps2C, or cps2D in the serotype 2 strain D39 did not affect the ability to transfer capsule to the cell wall. Deletion of cps2C or cps2D, which encode two domains of an autophosphorylating tyrosine kinase, resulted in the production of only short-chain polymers. The function of Cps2A is unknown, and the polymer laddering pattern of the cps2A deletion mutants appeared similar to that of the parent, although the total amount of capsule was decreased. Loss of Cps2B, a tyrosine phosphatase and a kinase inhibitor, resulted in an increase in capsule amount and a normal ladder pattern. However, Cps2B mutants exhibited reduced virulence following intravenous inoculation of mice and were unable to colonize the nasopharynx, suggesting a diminished capacity to sense or respond to these environments. In D39 and its isogenic mutants, the amounts of capsule and tyrosine-phosphorylated Cps2D (Cps2D∼P) correlated directly. In contrast, restoration of type 2 capsule production followed by deletion of cps2B in Rx1, a laboratory passaged D39 derivative containing multiple uncharacterized mutations, resulted in decreased capsule amounts but no alteration in Cps2D∼P levels. Thus, a factor outside the capsule locus, which is either missing or defective in the Rx1 background, is important in the control of capsule synthesis.

DIAGNOSIS AND TREATMENT: MANAGEMENT OF IDIOPATHIC THROMBOCYTOPENIC PURPURA

PEDIATRICS ◽  
1964 ◽  
Vol 33 (6) ◽  
pp. 979-980
Author(s):  
Irving Schulman
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Systemic Disease ◽  
Purpura Fulminans ◽  
Systemic Infection ◽  
Bone Marrow Examination ◽  
Rational Approach ◽  
Thrombocytopenic Purpura ◽  
Disease States ◽  
History Of ◽  
Acute Itp

THE TERM idiopathic thrombocytopenic purpura (ITP) should be reserved for that hemorrhagic disorder characterized by a subnormal platelet count (usually below 50,000/cu mm) in the presence of a normal marrow containing normal or increased megakaryocytes and the absence of systemic disease capable of inducing thrombopenia. Bone marrow examination is mandatory to rule out leukemia, other infiltrative disorders, and hypoplastic and aplastic states; an L.E. preparation is indicated as are the careful search for systemic infection and renal disease and the detailed inquiry concerning drug ingestion. Although no specific antecedent event can be identified in most cases of ITP, it is recognized that some of the common childhood exanthemata may occasionally be followed by thrombocytopenic purpura (e.g., rubella, rubeola, varicella). The rational approach to treatment must be based upon understanding of the natural history of the disease. Acute ITP has an excellent prognosis and approximately 80% affected children will make a complete and permanent recovery without specific therapy. Of these, three-quarters will recover within 3 months of onset, most within 4 to 6 weeks. Approximately 20% of cases will persist longer than 6 months and are then usually designated as chronic. The mortality rate in acute ITP is extremely low and most of the urgency for treatment stems from concern over central nervous system hemorrhage. It seems clear that the incidence of CNS bleeding is no greater than 2-4% and that in most series reporting a greater incidence cases were not limited to ITP but included instances of thrombotic thrombocytopenic purpura and purpura fulminans, i.e., disease states associated with vasculitis.

scholarly journals Outbreaks of canid herpesvirus 1 disease in puppies in southern Brazil

2015 ◽  
Vol 35 (6) ◽  
pp. 557-561 ◽  
Author(s):  
Juliana F. Cargnelutti ◽  
Eduardo K. Masuda ◽  
Mariana G. Neuls ◽  
Rudi Weiblen ◽  
Eduardo F. Flores
Keyword(s):  
Phylogenetic Analyses ◽  
Systemic Disease ◽  
Reproductive Age ◽  
Nucleotide Sequencing ◽  
Southern Brazil ◽  
Virus Identification ◽  
Clinicopathological Findings ◽  
Antibody Titers ◽  
Herpesvirus 1 ◽  
Severe Systemic Disease

Abstract: Canid herpesvirus 1 (CHV-1) is a widespread pathogen of dogs and produces infertility, abortions and severe systemic disease in young puppies. Clinical data indicate the circulation of CHV-1 among Brazilian dogs yet definitive diagnosis has rarely been accomplished. This article describes the clinicopathological findings of four independent cases/outbreaks of neonatal disease by CHV-1 in Bulldog puppies followed by virus identification and genetic characterization. Three events occurred in a kennel holding dogs of different breeds at reproductive age (March 2013, October 2013 and April 2014). Puppies from three French or English Bulldog litters, aging 9 to 30 days were affected, presenting dyspnea, agonic breathing, pale mucous, abdominal pain and tension, evolving to death within about 24 hours. At necropsy, the puppies presented necrohemorrhagic hepatitis, multifocal and moderate necrohemorrhagic nephritis and fibrinonecrotic interstitial pneumonia. Virus isolation was positive in clinical specimens from one litter and CHV-1 DNA was detected by PCR in tissues from all four cases. Virus-neutralizing assays with samples of the affected kennel revealed 9/12 adult animals with high antibody titers to CHV-1. Nucleotide sequencing of glycoprotein B, C and D genes revealed 99-100% of identity among the viruses and with CHV-1 sequences available in GenBank. Phylogenetic analyses of gC sequences showed a segregation of the samples, even among three isolates from the same kennel. These findings support CHV-1 infection as the cause of disease and death in these dog litters, reinforcing the need for correct etiologic diagnosis, prevention and immunization against CHV-1 in dogs from Southern Brazil.

scholarly journals Identification and Characterization of thecps Locus of Streptococcus suis Serotype 2: the Capsule Protects against Phagocytosis and Is an Important Virulence Factor

1999 ◽  
Vol 67 (4) ◽  
pp. 1750-1756 ◽  
Author(s):  
Hilde E. Smith ◽  
Marloes Damman ◽  
Joeke van der Velde ◽  
Frans Wagenaar ◽  
Henk J. Wisselink ◽  
...  
Keyword(s):  
Insertional Mutagenesis ◽  
Capsular Polysaccharide ◽  
Streptococcus Suis ◽  
Open Reading Frames ◽  
Transcriptional Unit ◽  
Polysaccharide Biosynthesis ◽  
Capsule Production ◽  
Important Virulence Factor ◽  
Isogenic Mutants

ABSTRACT To study the role of the capsule of Streptococcus suisserotype 2 in virulence, we generated two isogenic mutants disturbed in capsule production. For that purpose, we first cloned and characterized a major part of the capsular polysaccharide biosynthesis (cps) locus of S. suis serotype 2. Based on the established sequence, 14 open reading frames (ORFs), designated Orf2Z, Orf2Y, Orf2X, and Cps2A to Cps2K, were identified. Twelve ORFs belonged to a single transcriptional unit. The gene products of 11 of these ORFs showed similarity to proteins involved in polysaccharide biosynthesis of other gram-positive microorganisms. Nonencapsulated isogenic mutants were generated in the cps2B and cps2EF genes by insertional mutagenesis. In contrast to the wild-type S. suis serotype 2 strain, the nonencapsulated strains were highly sensitive to ingestion by porcine alveolar lung macrophages in vitro. More importantly, the nonencapsulated mutant strains were completely avirulent in young germfree pigs after intranasal inoculation. These observations indicate that the capsule of S. suis serotype 2 plays an essential role in the pathogenesis of S. suisserotype 2 infections.

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