A killed, genetically engineered derivative of a wild-type extraintestinal pathogenic E. coli strain is a vaccine candidate

Russo, Thomas A.; Beanan, Janet M.; Olson, Ruth; Genagon, Stacy A.; MacDonald, Ulrike; Cope, John J.; Davidson, Bruce A.; Johnston, Brian; Johnson, James R.

doi:10.1016/j.vaccine.2007.01.100

Cited by 35 publications

(27 citation statements)

References 55 publications

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“…Flow-cytometric assessment of antibody binding was performed as described previously (42). In brief, the appropriate strains were grown in LB medium, diluted to 1 ϫ 10 6 CFU, washed in 100 l of 1ϫ PBS, resuspended in 100 l of 1:100-diluted preimmune, nonimmune, or anti-K1 immune polyclonal mouse antiserum (complement inactivated by heating at 56°C for 30 min), and incubated for 60 min at 37°C with constant rotation.…”

Section: Methodsmentioning

confidence: 99%

The K1 Capsular Polysaccharide from Acinetobacter baumannii Is a Potential Therapeutic Target via Passive Immunization

et al. 2013

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fThe emergence of extremely resistant and panresistant Gram-negative bacilli, such as Acinetobacter baumannii, requires consideration of nonantimicrobial therapeutic approaches. The goal of this report was to evaluate the K1 capsular polysaccharide from A. baumannii as a passive immunization target. Its structure was determined by a combination of mass spectrometric and nuclear magnetic resonance (NMR) techniques. Molecular mimics that might raise the concern for autoimmune disease were not identified. Immunization of CD1 mice demonstrated that the K1 capsule is immunogenic. The monoclonal antibody (MAb) 13D6, which is directed against the K1 capsule from A. baumannii, was used to determine the seroprevalence of the K1 capsule in a collection of 100 A. baumannii strains. Thirteen percent of the A. baumannii isolates from this collection were seroreactive to MAb 13D6. Opsonization of K1-positive strains, but not K1-negative strains, with MAb 13D6 significantly increased neutrophil-mediated bactericidal activity in vitro (P < 0.05). Lastly, treatment with MAb 13D6 3 and 24 h after bacterial challenge in a rat soft tissue infection model resulted in a significant decrease in the growth/survival of a K1-positive strain compared to that of a K1-negative strain or to treatment with a vehicle control (P < 0.0001). These data support the proof of principle that the K1 capsule is a potential therapeutic target via passive immunization. Other serotypes require assessment, and pragmatic challenges exist, such as the need to serotype infecting strains and utilize serotype-specific therapy. Nonetheless, this approach may become an important therapeutic option with increasing antimicrobial resistance and a diminishing number of active antimicrobials.

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Section: Methodsmentioning

confidence: 99%

The K1 Capsular Polysaccharide from Acinetobacter baumannii Is a Potential Therapeutic Target via Passive Immunization

et al. 2013

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“…Flow-cytometric assessment of antibody binding was performed as described previously (36). In brief, the appropriate strains were grown in LB medium, diluted to 1 ϫ 10 6 CFU, washed in 100 l of 1ϫ phosphatebuffered saline (PBS) (pH 7.2), resuspended in 100 l of 1:100-diluted hybridoma supernatants (complement inactivated), and incubated while rotating for 60 min at 37°C.…”

Section: Bacterialmentioning

confidence: 99%

The K1 Capsular Polysaccharide of Acinetobacter baumannii Strain 307-0294 Is a Major Virulence Factor

et al. 2010

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Acinetobacter baumannii is a pathogen of increasing medical importance with a propensity to be multidrug resistant, thereby making treatment challenging. Little is known of virulence traits in A. baumannii. To identify virulence factors and potential drug targets, random transposon (Tn) mutants derived from the A. baumannii strain AB307-0294 were screened to identify genes essential for growth in human ascites fluid in vitro, an inflammatory exudative fluid. These studies led to the identification of two genes that were predicted to be required for capsule polymerization and assembly. The first, ptk, encodes a putative protein tyrosine kinase (PTK), and the second, epsA, encodes a putative polysaccharide export outer membrane protein (EpsA). Monoclonal antibodies used in flow cytometric and Western analyses confirmed that these genes are required for a capsule-positive phenotype. A capsule-positive phenotype significantly optimized growth in human ascites fluid, survival in human serum, and survival in a rat soft tissue infection model. Importantly, the clearance of the capsule-minus mutants AB307.30 (ptk mutant, capsule minus) and AB307.45 (epsA mutant, capsule minus) was complete and durable. These data demonstrated that the K1 capsule from AB307-0294 was an important protectin. Further, these data suggested that conserved proteins, which contribute to the capsule-positive phenotype, are potential antivirulence drug targets. Therefore, the results from this study have important biologic and translational implications and, to the best of our knowledge, are the first to address the role of capsule in the pathogenesis of A. baumannii infection.

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“…There are (219). Later studies involved vaccines directed against particular virulence factors ( Table 2).…”

Section: Weapons Systems: Current and Proposed Treatments And Vaccinementioning

confidence: 99%

Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract

2010

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Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is a substantial economic and societal burden-a formidable public health issue. Symptomatic UTI causes significant discomfort in infected patients, results in lost productivity, predisposes individuals to more serious infections, and usually necessitates antibiotic therapy. There is no licensed vaccine available for prevention of UTI in humans in the United States, likely due to the challenge of targeting a relatively heterogeneous group of pathogenic strains in a unique physiological niche. Despite significant advances in the understanding of UPEC biology, mechanistic details regarding the host response to UTI and full comprehension of genetic loci that influence susceptibility require additional work. Currently, there is an appreciation for the role of classic innate immune responses-from pattern receptor recognition to recruitment of phagocytic cells-that occur during UPEC-mediated UTI. There is, however, a clear disconnect regarding how factors involved in the innate immune response to UPEC stimulate acquired immunity that facilitates enhanced clearance upon reinfection. Unraveling the molecular details of this process is vital in the development of a successful vaccine for prevention of human UTI. Here, we survey the current understanding of host responses to UPEC-mediated UTI with an eye on molecular and cellular factors whose activity may be harnessed by a vaccine that stimulates lasting and sterilizing immunity. MISSION: ERADICATE UPEC-MEDIATED UTIUrinary tract infection (UTI) is one of the most common infections in humans. Bacteria present in fecal matter inoculate the periurethral area, then the bladder (124, 176, 291), causing symptoms clinically termed cystitis. Left untreated, bacteria ascend the ureters to the kidney and establish a secondary infection, acute pyelonephritis. At this juncture, there is risk of permanent renal scarring, and bacteria can access the bloodstream (282). It is estimated that 40% of women and 12% of men will experience a symptomatic UTI, with incidences peaking in their early 20s or after age 85, respectively (75, 185). Approximately 25% of these women will experience recurrence within 6 to 12 months (75, 185). Uropathogenic Escherichia coli (UPEC) is the most common etiological agent responsible for uncomplicated UTI (93, 94,282). Uropathogenic strains are classified as extraintestinal pathogenic E. coli, a broad grouping of E. coli that cause diseases other than gastroenteritis and typically lack a type III secretion system (171,220,221,283,284). Nonetheless, UPEC strains express an assortment of virulence and fitness factors that aid in successful colonization of the mammalian urinary tract (126,136). In the United States alone, the estimated annual societal cost of UTI is more than 3 billion dollars (159).Despite a relatively in-depth knowledge base for UPEC physiology and virulence mechanisms (reviewed in references 54, 126, 136, and 284), no licensed vaccine to prevent UTI exists in the Un...

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A killed, genetically engineered derivative of a wild-type extraintestinal pathogenic E. coli strain is a vaccine candidate

Cited by 35 publications

References 55 publications

The K1 Capsular Polysaccharide from Acinetobacter baumannii Is a Potential Therapeutic Target via Passive Immunization

The K1 Capsular Polysaccharide from Acinetobacter baumannii Is a Potential Therapeutic Target via Passive Immunization

The K1 Capsular Polysaccharide of Acinetobacter baumannii Strain 307-0294 Is a Major Virulence Factor

Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract

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