Publications by authors named "David A Haake"

Leptospirosis, the most widespread zoonotic disease in the world, is broadly understudied in multi-host wildlife systems. Knowledge gaps regarding Leptospira circulation in wildlife, particularly in densely populated areas, contribute to frequent misdiagnoses in humans and domestic animals. We assessed Leptospira prevalence levels and risk factors in five target wildlife species across the greater Los Angeles region: striped skunks (Mephitis mephitis), raccoons (Procyon lotor), coyotes (Canis latrans), Virginia opossums (Didelphis virginiana), and fox squirrels (Sciurus niger).

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Leptospirosis is an archetypal One Health problem as described in the companion Currents in One Health article in the October 2022 issue of the Journal of the American Veterinary Medical Association by Sykes et al. A thorough understanding of leptospirosis requires a detailed analysis of the elaborate interplay among pathogenic leptospiral strains, host species, and the environment. Such an understanding is required to inform appropriate preventative measures including vaccine design, prophylaxis efforts, educational programs that help to reduce exposure to pathogenic spirochetes, as well as policy development.

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Article Synopsis
  • * Recent events, including climate change and the COVID-19 pandemic, have increased the risk of leptospirosis outbreaks due to changes in environmental conditions and human-animal interactions, leading to under-recognition of the disease.
  • * Understanding and managing leptospirosis requires collaboration among physicians, veterinarians, and public health experts, with recent advancements improving diagnostics, prevention strategies, and educational outreach.
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A One Health approach to the epidemiology, management, surveillance, and control of leptospirosis relies on accessible and accurate diagnostics that can be applied to humans and companion animals and livestock. Diagnosis should be multifaceted and take into account exposure risk, clinical presentation, and multiple direct and/or indirect diagnostic approaches. Methods of direct detection of spp.

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Urinary tract infections (UTIs) are among the most common bacterial infections in the United States and are a major driver of antibiotic use, both appropriate and inappropriate, across healthcare settings. Novel UTI diagnostics are a strategy that might enable better UTI treatment. Members of the Antibacterial Resistance Leadership Group Laboratory Center and the Infectious Diseases Society of America Diagnostics Committee convened to envision ideal future UTI diagnostics, with a view towards improving delivery of healthcare, patient outcomes and experiences, and antibiotic use, addressing which types of UTI diagnostics are needed and how companies might approach development of novel UTI diagnostics.

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The virulence mechanisms required for infection and evasion of immunity by pathogenic species remain poorly understood. A number of surface proteins have been discovered, lying at the interface between the pathogen and host. Among these proteins, the functional properties of the Lig (leptospiral immunoglobulin-like domain) proteins have been examined most thoroughly.

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The wide variety of pathogenic serovars and the weak protection offered by the available vaccines encourage the search for protective immunogens against leptospirosis. We found that the secretin GspD of the type II secretion system (T2S) of serovar Canicola was highly conserved amongst pathogenic serovars and was expressed in vivo during infection, as shown by immunohistochemistry. Convalescent sera of hamsters, dogs, and cows showed the presence of IgG antibodies, recognizing a recombinant version of this protein expressed in (rGspDLC) in Western blot assays.

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Bloodstream infections are a leading cause of morbidity and mortality. Molecular rapid diagnostic tests (mRDTs) are transforming care for patients with bloodstream infection by providing the opportunity to dramatically shorten times to effective therapy and speeding de-escalation of overly broad empiric therapy. However, because of the novelty of these tests which provide information regarding microbial identification and whether specific antibiotic-resistance mutations were detected, many front-line providers still delay final decisions until complete phenotypic susceptibility results are available several days later.

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Background: The syphilis epidemic continues to cause substantial morbidity and mortality worldwide, particularly in low- and middle-income countries, despite several recent disease control initiatives. Though our understanding of the pathogenesis of this disease and the biology of the syphilis agent, Treponema pallidum subsp. pallidum has improved over the last two decades, further research is necessary to improve clinical diagnosis and disease management protocols.

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Urine culture and sensitivity (C&S) remains the gold standard diagnostic for urinary tract infections (UTI). To reduce the use of inaccurate or broad-spectrum empiric antimicrobials, rapid identification and quantification (IDQ) and antimicrobial susceptibility testing (AST) with results within 30 and 150 min, respectively, are under development. To assess the impact of rapid diagnostics, five UTI vignettes were constructed, and ninety-one United States physicians were surveyed regarding their diagnostic, management, and antimicrobial choices before and after IDQ and AST results.

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Many strains of the spirochete serovar Pomona express the osmotically inducible sphingomyelinase gene at much higher levels than strains from other serovars. We developed a new green fluorescent protein (GFP) reporter plasmid to examine gene expression determinants. The vector enables the fusion of the test promoter to the ribosome-binding site and coding region of We fused the promoters from the serovar Lai strain 56601 and from the serovar Pomona strain LC82-25 to to examine the molecular determinants of differential expression between the two strains.

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Introduction And Hypothesis: Acute, uncomplicated cystitis is one of the most common bacterial infections seen in clinical practice. Quality improvement and antibiotic stewardship efforts to optimize cystitis management rely on clinicians managing patients in a manner recommended by experts and guidelines. However, it is unclear if recent recommendations for cystitis from experts and guidelines from US medical societies that provide recommendations are well aligned.

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In this manuscript, we describe a transposon sequencing (Tn-Seq) technique to identify and quantify Leptospira interrogans mutants altered in fitness during infection of Golden Syrian hamsters. Tn-Seq combines random transposon mutagenesis with the power of high-throughput sequencing technology. Animals are challenged with a pool of transposon mutants (input pool), followed by harvesting of blood and tissues a few days later to identify and quantify the number of mutants in each organ (output pools).

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Leptospirosis is a widespread zoonosis, potentially severe in humans, caused by spirochetal bacteria, Leptospira interrogans (L. interrogans). Host defense mechanisms involved in leptospirosis are poorly understood.

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Lipoproteins are lipid-modified proteins that dominate the spirochetal proteome. While found in all bacteria, spirochetal lipoproteins have unique features and play critical roles in spirochete biology. For this reason, considerable effort has been devoted to determining how the lipoproteome is generated.

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Leptospirosis is the most widespread zoonosis and is considered a major public health problem worldwide. Currently, there is no widely available vaccine against leptospirosis for use in humans. A purified, recombinant subunit vaccine that includes the last six immunoglobulin-like (Ig-like) domains of the leptospiral protein LigA (LigA7'-13) protects against lethal infection but not renal colonization after challenge by Leptospira interrogans.

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Article Synopsis
  • Pathogenic Leptospira species cause leptospirosis, a serious zoonotic disease, but understanding their virulence is limited due to a lack of genetic research tools.
  • The study utilized transposon sequencing (Tn-Seq) to analyze the in vivo fitness of 42 Leptospira interrogans mutants in hamsters, focusing on their presence in various tissues post-infection.
  • Findings revealed specific mutants associated with reduced fitness and virulence, particularly those inserted in the lic12327 gene, showcasing the effectiveness of Tn-Seq for identifying virulence factors in these bacteria.
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The pathogen Leptospira interrogans is a highly motile spirochete that causes acute and fulminant infections in humans and other accidental hosts. Hematogenous dissemination is important for infection by the pathogen but remains poorly understood because few animal model studies have used sensitive tools to quantify the bacteria. We evaluated the kinetics of leptospiral infection in Golden Syrian hamsters by a sensitive quantitative real-time PCR (TaqMan) with lipl32 as the target gene.

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Leptospirosis, caused by spirochetes of the genus Leptospira, is a globally widespread, neglected and emerging zoonotic disease. While whole genome analysis of individual pathogenic, intermediately pathogenic and saprophytic Leptospira species has been reported, comprehensive cross-species genomic comparison of all known species of infectious and non-infectious Leptospira, with the goal of identifying genes related to pathogenesis and mammalian host adaptation, remains a key gap in the field. Infectious Leptospira, comprised of pathogenic and intermediately pathogenic Leptospira, evolutionarily diverged from non-infectious, saprophytic Leptospira, as demonstrated by the following computational biology analyses: 1) the definitive taxonomy and evolutionary relatedness among all known Leptospira species; 2) genomically-predicted metabolic reconstructions that indicate novel adaptation of infectious Leptospira to mammals, including sialic acid biosynthesis, pathogen-specific porphyrin metabolism and the first-time demonstration of cobalamin (B12) autotrophy as a bacterial virulence factor; 3) CRISPR/Cas systems demonstrated only to be present in pathogenic Leptospira, suggesting a potential mechanism for this clade's refractoriness to gene targeting; 4) finding Leptospira pathogen-specific specialized protein secretion systems; 5) novel virulence-related genes/gene families such as the Virulence Modifying (VM) (PF07598 paralogs) proteins and pathogen-specific adhesins; 6) discovery of novel, pathogen-specific protein modification and secretion mechanisms including unique lipoprotein signal peptide motifs, Sec-independent twin arginine protein secretion motifs, and the absence of certain canonical signal recognition particle proteins from all Leptospira; and 7) and demonstration of infectious Leptospira-specific signal-responsive gene expression, motility and chemotaxis systems.

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The Miller Hypothesis.

For Immunopathol Dis Therap

January 2016

The immune response is a cornerstone in the body's struggle against microbial pathogens. In ways that we do not yet completely understand, the mammalian immune response has evolved to identify proteins of pathogens that are either important virulence factors or key immunoprotective targets. Professor James N.

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Pathogenic members of the genus Leptospira are the causative agents of leptospirosis, a neglected disease of public and veterinary health concern. Leptospirosis is a systemic disease that in its severest forms leads to renal insufficiency, hepatic dysfunction, and pulmonary failure. Many strains of Leptospira produce hemolytic and sphingomyelinase activities, and a number of candidate leptospiral hemolysins have been identified based on sequence similarity to well-characterized bacterial hemolysins.

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Patients with persistent lower urinary tract symptoms and negative urine cultures are often difficult to treat. Infection may go undetected in these patients because the concentrations of bacteria in their urine are beneath the threshold of standard urine culture techniques. Empiric treatment may result in temporary relief, followed by recurrent symptoms.

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Background: Leptospirosis is a zoonosis caused by highly motile, helically shaped bacteria that penetrate the skin and mucous membranes through lesions or abrasions, and rapidly disseminate throughout the body. Although the intraperitoneal route of infection is widely used to experimentally inoculate hamsters, this challenge route does not represent a natural route of infection.

Methodology/principal Findings: Here we describe the kinetics of disease and infection in hamster model of leptospirosis after subcutaneous and intradermal inoculation of Leptospira interrogans serovar Copenhageni, strain Fiocruz L1-130.

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