Browsing by Subject "Pathogens"

Now showing 1 - 7 of 7
  • Thumbnail Image
    Item
    322. Evaluation of the BioFire® Bone and Joint Infection (BJI) Panel for the Detection of Microorganisms and Antimicrobial Resistance Genes in Synovial Fluid Specimens
    (Oxford University Press, 2020-12) Graue, Corrin; Schmitt, Bryan H.; Waggoner, Amy; Laurent, Frederic; Abad, Lelia; Bauer, Thomas; Mazariegos, Irving; Balada-Llasat, Joan-Miquel; Horn, Jarid; Wolk, Donna; Jefferis, Alexa; Hermans, Mirjam; Verhoofstad, Irma; Butler-Wu, Susan; Umali-Wilcox, Minette; Murphy, Caitlin N.; Cabrera, Barbara J.; Esteban, Jaime; Macias-Valcayo, Alicia; Craft, David; von Bredow, Benjamin; Leber, Amy; Everhart, Kathy; Dien Bard, Jennifer; Mestas, Jvier; Daly, Judy; Barr, Rebecca; Kensinger, Bart; Pons, Benedicte; Jay, Corinne; Pathology and Laboratory Medicine, School of Medicine
    Background Bone and Joint Infections (BJIs) present with non-specific symptoms that may include pain, swelling, and fever and are associated with high morbidity and significant risk of mortality. BJIs can be caused by a variety of bacteria and fungi, including anaerobes and microorganisms that can be challenging to culture or identify by traditional microbiological methods. Clinicians primarily rely on culture to identify the pathogen(s) responsible for infection. The BioFire® Bone and Joint Infection (BJI) Panel (BioFire Diagnostics, Salt Lake City, UT) is designed to detect 15 gram-positive bacteria (including seven anaerobes), 14 gram-negative bacteria (including one anaerobe), two yeast, and eight antimicrobial resistance (AMR) genes from synovial fluid specimens in about an hour. The objective of this study was to evaluate the performance of an Investigational Use Only (IUO) version of the BioFire BJI Panel compared to various reference methods. Methods Remnant synovial fluid specimens, which were collected for routine clinical care at 13 study sites in the US and Europe, underwent testing using an IUO version of the BioFire BJI Panel. Performance of this test was determined by comparison to Standard of Care (SoC) consisting of bacterial culture performed at each study site according to their routine procedures. Results A total of 1544 synovial fluid specimens were collected and tested with the BioFire BJI Panel. The majority of specimens were from knee joints (77.9%) and arthrocentesis (79.4%) was the most common collection method. Compared to SoC culture, overall sensitivity was 90.2% and specificity was 99.8%. The BioFire BJI Panel yielded a total of 268 Detected results, whereas SoC yielded a total of 215 positive results for on-panel analytes. Conclusion The BioFire BJI Panel is a sensitive, specific, and robust test for rapid detection of a wide range of analytes in synovial fluid specimens. The number of microorganisms and resistance genes included in the BioFire BJI Panel, together with a reduced time-to-result and increased diagnostic yield compared to culture, is expected to aid in the timely diagnosis and appropriate management of BJIs.
  • Thumbnail Image
    Item
    Five-year resistance trends in pathogens causing healthcare-associated infections at a multi-hospital healthcare system in Saudi Arabia, 2015-2019
    (Elsevier, 2021) Al Mutair, Abbas; Alhumaid, Saad; Al Alawi, Zainab; Zaidi, Abdul Rehman Z.; Alzahrani, Ahmed J.; Al-Tawfiq, Jaffar A.; Al-Shammari, Haifa; Rabaan, Ali A.; Khojah, Osamah; Al-Omari, Awad; Medicine, School of Medicine
    Objectives: Awareness of antimicrobial resistance (AMR) patterns in a given healthcare setting is important to inform the selection of appropriate antimicrobial therapy to reduce the further rise and spread of AMR as well as the rate of healthcare-associated infections (HAIs) and multidrug-resistant (MDR) organisms. We aimed to describe resistance patterns to several antimicrobial agents in pathogens causing HAIs isolated from patients using data gathered at three private tertiary-care hospitals in Saudi Arabia. Methods: Data on trends in AMR among bacteria causing HAIs and MDR events in children and adults at three private hospitals were collected retrospectively (2015-2019) using surveillance data. Results: Over the 5-year period, 29 393 pathogens caused 17 539 HAIs in 15 259 patients. Approximately 57.3% of patients were female and the mean age was 38.4 ± 16.8 years (81.4% adults, 18.6% children). Gram-negative pathogens were four times more likely to cause HAIs compared with Gram-positive bacteria (79.3% vs. 20.7%). Ranking of causative pathogens in decreasing order was Escherichia coli (42.2%), Klebsiella spp. (16.8%) and Staphylococcus aureus (13.9%). Acinetobacter spp. were the only pathogens to decrease significantly (7% reduction; P = 0.033). The most common resistant pathogens were extended-spectrum cephalosporin-resistant E. coli (37.1%), extended-spectrum cephalosporin-resistant Klebsiella (27.8%), carbapenem-non-susceptible Acinetobacter spp. (19.5%), carbapenem-non-susceptible Pseudomonas aeruginosa (19.2%) and methicillin-resistant S. aureus (18.6%). Conclusion: National collaboration is required by prompt feedback to local authorities to tackle regional differences in AMR. This can help plan timely containment interventions to stop and contain microbial threats and swiftly assess their impact.
  • Thumbnail Image
    Item
    A Same-Genus Screening Approach Reveals Novel Effectors and New Possibilities for Investigating Chlamydia Pathogenesis
    (American Society for Microbiology, 2021-06) Ryan, John D.; Nelson, David E.; Microbiology and Immunology, School of Medicine
    Chlamydiae are obligate intracellular pathogens that rely on secreted effector proteins to establish their intracellular niche. In this issue of the Journal of Bacteriology, Yanatori et al describe a screen for C. pneumoniae effectors, performed in C. trachomatis, which identified several new proteins that are translocated during infection (Yanatori, Miura et al. 2021). More broadly, they demonstrate how new genetic approaches in C. trachomatis can be used to characterize the virulence factors of other Chlamydia species.
  • Thumbnail Image
    Item
    Streptococcus agalactiae cadD alleviates metal stress and promotes intracellular survival in macrophages and ascending infection during pregnancy
    (Springer Nature, 2022-09-14) Korir, Michelle L.; Doster, Ryan S.; Lu, Jacky; Guevara, Miriam A.; Spicer, Sabrina K.; Moore, Rebecca E.; Francis, Jamisha D.; Rogers, Lisa M.; Haley, Kathryn P.; Blackman, Amondrea; Noble, Kristen N.; Eastman, Alison J.; Williams, Janice A.; Damo, Steven M.; Boyd, Kelli L.; Townsend, Steven D.; Serezani, C. Henrique; Aronoff, David M.; Manning, Shannon D.; Gaddy, Jennifer A.; Medicine, School of Medicine
    Perinatal infection with Streptococcus agalactiae, or Group B Streptococcus (GBS), is associated with preterm birth, neonatal sepsis, and stillbirth. Here, we study the interactions of GBS with macrophages, essential sentinel immune cells that defend the gravid reproductive tract. Transcriptional analyses of GBS-macrophage co-cultures reveal enhanced expression of a gene encoding a putative metal resistance determinant, cadD. Deletion of cadD reduces GBS survival in macrophages, metal efflux, and resistance to metal toxicity. In a mouse model of ascending infection during pregnancy, the ΔcadD strain displays attenuated bacterial burden, inflammation, and cytokine production in gestational tissues. Furthermore, depletion of host macrophages alters cytokine expression and decreases GBS invasion in a cadD-dependent fashion. Our results indicate that GBS cadD plays an important role in metal detoxification, which promotes immune evasion and bacterial proliferation in the pregnant host.
  • Thumbnail Image
    Item
  • Thumbnail Image
    Item
    What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira.
    (PLOS, 2016-02) Fouts, Derrick E.; Matthias, Michael A.; Adhikarla, Haritha; Adler, Ben; Amorim-Santos, Luciane; Berg, Douglas E.; Bulach, Dieter; Buschiazzo, Alejandro; Chang, Yung-Fu; Galloway, Renee L.; Haake, David A.; Haft, Daniel H.; Hartskeerl, Rudy; Ko, Albert I.; Levett, Paul N.; Matsunaga, James; Mechaly, Ariel E.; Monk, Jonathan M.; Nascimento, Ana L. T.; Nelson, Karen E.; Palsson, Bernhard; Peacock, Sharon J.; Picardeau, Mathieu; Ricaldi, Jessica N.; Thaipandungpanit, Janjira; Wunder, Elsio A.; Yang, X. Frank; Zhang, Jun-Jie; Vinetz, Joseph M.; Department of Microbiology & Immunology, IU School of Medicine
    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. By identifying large scale changes in infectious (pathogenic and intermediately pathogenic) vs. non-infectious Leptospira, this work provides new insights into the evolution of a genus of bacterial pathogens. This work will be a comprehensive roadmap for understanding leptospirosis pathogenesis. More generally, it provides new insights into mechanisms by which bacterial pathogens adapt to mammalian hosts.
  • Thumbnail Image
    Item
    Wood cookstove use is associated with gastric cancer in Central America and mediated by host genetics
    (Springer Nature, 2023-10) Rifkin, Samara B.; Miller, Anna K.; Montalvan‑Sanchez, Eleazar E.; Norwood, Dalton A.; Martinez, Enrique; Waterboer, Tim; Beasley, T. Mark; Dominguez, Ricardo L.; Williams, Scott M.; Morgan, Douglas R.; Medicine, School of Medicine
    Biomass cookstove food preparation is linked to aero-digestive cancers, mediated by ingested and inhaled carcinogens (e.g., heterocyclic amines, and polycyclic aromatic hydrocarbons). We investigated the association between gastric adenocarcinoma, wood cookstove use, H. pylori CagA infection and risk modification by variants in genes that metabolize and affect the internal dose of carcinogens. We conducted a population-based, case–control study (814 incident cases, 1049 controls) in rural Honduras, a high-incidence region with a homogeneous diet and endemic H. pylori infection, primarily with the high-risk CagA genotype. We investigated factors including wood cookstove use, H. pylori CagA serostatus, and 15 variants from 7 metabolizing genes, and the interactions between wood stove use and the genetic variants. Male sex (OR 2.0, 1.6–2.6), age (OR 1.04, 1.03–1.05), wood cookstove use (OR 2.3, 1.6–3.3), and CagA serostatus (OR 3.5, 2.4–5.1) and two SNPs in CYP1B1 (rs1800440 and rs1056836) were independently associated with gastric cancer in multivariate analysis. In the final multivariate model, a highly significant interaction (OR 3.1, 1.2–7.8) was noted between wood cookstove use and the rs1800440 metabolizing genotype, highlighting an important gene-environment interaction. Lifetime wood cookstove use associates with gastric cancer risk in the high-incidence regions of Central America, and the association is dependent on the rs1800440 genotype in CYP1B1. H. pylori CagA infection, wood cookstove use and the rs1800440 genotype, all of which are highly prevalent, informs who is at greatest risk from biomass cookstove use.