18 results on '"Suzanne Hower"'
Search Results
2. Staphylococcus epidermidis Boosts Innate Immune Response by Activation of Gamma Delta T Cells and Induction of Perforin-2 in Human Skin
- Author
-
Irena Pastar, Katelyn O’Neill, Laura Padula, Cheyanne R. Head, Jamie L. Burgess, Vivien Chen, Denisse Garcia, Olivera Stojadinovic, Suzanne Hower, Gregory V. Plano, Seth R. Thaller, Marjana Tomic-Canic, and Natasa Strbo
- Subjects
perforin-2/mpeg-1 ,human skin ,innate immunity ,Staphylococcus epidermidis ,gamma delta T cells ,cytotoxicity ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Perforin-2 (P-2) is an antimicrobial protein with unique properties to kill intracellular bacteria. Gamma delta (GD) T cells, as the major T cell population in epithelial tissues, play a central role in protective and pathogenic immune responses in the skin. However, the tissue-specific mechanisms that control the innate immune response and the effector functions of GD T cells, especially the cross-talk with commensal organisms, are not very well understood. We hypothesized that the most prevalent skin commensal microorganism, Staphylococcus epidermidis, may play a role in regulating GD T cell-mediated cutaneous responses. We analyzed antimicrobial protein P-2 expression in human skin at a single cell resolution using an amplified fluorescence in situ hybridization approach to detect P-2 mRNA in combination with immunophenotyping. We show that S. epidermidis activates GD T cells and upregulates P-2 in human skin ex vivo in a cell-specific manner. Furthermore, P-2 upregulation following S. epidermidis stimulation correlates with increased ability of skin cells to kill intracellular Staphylococcus aureus. Our findings are the first to reveal that skin commensal bacteria induce P-2 expression, which may be utilized beneficially to modulate host innate immune responses and protect from skin infections.
- Published
- 2020
- Full Text
- View/download PDF
3. Comparative Effectiveness Study of Home-Based Interventions to Prevent CA-MRSA Infection Recurrence
- Author
-
Jonathan N. Tobin, Suzanne Hower, Brianna M. D’Orazio, María Pardos de la Gándara, Teresa H. Evering, Chamanara Khalida, Jessica Ramachandran, Leidy Johana González, Rhonda G. Kost, Kimberly S. Vasquez, Hermínia de Lencastre, Alexander Tomasz, Barry S. Coller, and Roger Vaughan
- Subjects
methicillin-resistant Staphylococcus aureus (MRSA) ,antibiotic-resistance ,skin and soft tissue infection (SSTI) ,community-based participatory research (CBPR) ,practice-based research network (PBRN) ,randomized clinical trial (RCT) ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Recurrent skin and soft tissue infections (SSTI) caused by Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) or Methicillin-Sensitive Staphylococcus aureus (CA-MSSA) present treatment challenges. This community-based trial examined the effectiveness of an evidence-based intervention (CDC Guidelines, topical decolonization, surface decontamination) to reduce SSTI recurrence, mitigate household contamination/transmission, and improve patient-reported outcomes. Participants (n = 186) were individuals with confirmed MRSA(+)/MSSA(+) SSTIs and their household members. During home visits; Community Health Workers/Promotoras provided hygiene instructions; a five-day supply of nasal mupirocin; chlorhexidine for body cleansing; and household disinfecting wipes (Experimental; EXP) or Usual Care Control (UC CON) pamphlets. Primary outcome was six-month SSTI recurrence from electronic health records (EHR). Home visits (months 0; 3) and telephone assessments (months 0; 1; 6) collected self-report data. Index patients and participating household members provided surveillance culture swabs. Secondary outcomes included household surface contamination; household member colonization and transmission; quality of life; and satisfaction with care. There were no significant differences in SSTI recurrence between EXP and UC in the intent-to-treat cohort (n = 186) or the enrolled cohort (n = 119). EXP participants showed reduced but non-significant colonization rates. EXP and UC did not differ in household member transmission, contaminated surfaces, or patient-reported outcomes. This intervention did not reduce clinician-reported MRSA/MSSA SSTI recurrence. Taken together with other recent studies that employed more intensive decolonization protocols, it is possible that a promotora-delivered intervention instructing treatment for a longer or repetitive duration may be effective and should be examined by future studies.
- Published
- 2021
- Full Text
- View/download PDF
4. Chronic wound microenvironment mediates selection of biofilm-forming multi drug resistant Staphylococcus epidermidis with capability to impair healing
- Author
-
Irena Pastar, Miroslav Dinic, Rebecca Verpile, Jingjing Meng, Jelena Marjanovic, Jamie Burgess, Lisa Plano, Suzanne Hower, Seth Thaller, Santanu Banerjee, Hadar Lev-Tov, and Marjana Tomic-Canic
- Abstract
Venous leg ulcers (VLU) are the most common chronic wounds characterized by bacterial biofilms and perturbed microbiome. Staphylococcus epidermidis is primarily known as skin commensal beneficial for the host, however, some strains can form biofilms and cause infections. By employing shotgun metagenomic sequencing we show that genetic signatures of antimicrobial resistance, adhesion and biofilm formation in VLU isolates correlate with in vitro bacterial traits. We demonstrate that the capability of chronic wound isolates to form biofilms and elicit IL-8 and IL-1β expression in human ex vivo wounds, correlates with the non-healing outcomes in patients with VLU. In contrast, commensal strains were incapable of surviving in the human ex vivo wounds. We show that major fitness traits of S. epidermis from VLU involve genes for resistance to methicillin and mupirocin, while the biofilm formation relied on the minimal number of genetic elements responsible for bacterial binding to fibronectin and fibrinogen. This underscores the importance of the emergence of treatment resistant virulent lineages in patients with non-healing wounds.
- Published
- 2023
5. Perforin-2 Breaches the Envelope of Phagocytosed Bacteria Allowing Antimicrobial Effectors Access to Intracellular Targets
- Author
-
Fangfang Bai, Mathias G. Lichtenheld, George P. Munson, Ryan McCormack, Gregory V. Plano, and Suzanne Hower
- Subjects
Pore Forming Cytotoxic Proteins ,Salmonella typhimurium ,0301 basic medicine ,Proteases ,030106 microbiology ,Immunology ,Virulence ,chemical and pharmacologic phenomena ,Article ,Bacterial cell structure ,Microbiology ,Mice ,03 medical and health sciences ,Phagocytosis ,Cell Wall ,Animals ,Immunology and Allergy ,Mice, Knockout ,Salmonella Infections, Animal ,biology ,Chemistry ,hemic and immune systems ,Periplasmic space ,biology.organism_classification ,030104 developmental biology ,Perforin ,Salmonella enterica ,biology.protein ,Bacteria ,Intracellular - Abstract
Perforin-2, the product of the MPEG1 gene, limits the spread and dissemination of bacterial pathogens in vivo. It is highly expressed in murine and human phagocytes, and macrophages lacking Perforin-2 are compromised in their ability to kill phagocytosed bacteria. In this study, we used Salmonella enterica serovar Typhimurium as a model intracellular pathogen to elucidate the mechanism of Perforin-2’s bactericidal activity. In vitro Perforin-2 was found to facilitate the degradation of Ags contained within the envelope of phagocytosed bacteria. In contrast, degradation of a representative surface Ag was found to be independent of Perforin-2. Consistent with our in vitro results, a protease-sensitive, periplasmic superoxide dismutase (SodCII) contributed to the virulence of S. Typhimurium in Perforin-2 knockout but not wild-type mice. In aggregate, our studies indicate that Perforin-2 breaches the envelope of phagocytosed bacteria, facilitating the delivery of proteases and other antimicrobial effectors to sites within the bacterial cell.
- Published
- 2018
6. Staphylococcus epidermidis Boosts Innate Immune Response by Activation of Gamma Delta T Cells and Induction of Perforin-2 in Human Skin
- Author
-
Olivera Stojadinovic, Suzanne Hower, Marjana Tomic-Canic, Katelyn O’Neill, Vivien Chen, Denisse Garcia, Natasa Strbo, Seth R. Thaller, Irena Pastar, Laura Padula, Cheyanne R. Head, Gregory V. Plano, and Jamie L. Burgess
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,T cell ,Population ,Immunology ,Human skin ,Biology ,medicine.disease_cause ,Microbiology ,perforin-2/mpeg-1 ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Staphylococcus epidermidis ,medicine ,Immunology and Allergy ,gamma delta T cells ,education ,innate immunity ,Original Research ,education.field_of_study ,Innate immune system ,Intracellular parasite ,biology.organism_classification ,030104 developmental biology ,medicine.anatomical_structure ,Staphylococcus aureus ,cytotoxicity ,human skin ,lcsh:RC581-607 ,030215 immunology - Abstract
Perforin-2 (P-2) is an antimicrobial protein with unique properties to kill intracellular bacteria. Gamma delta (GD) T cells, as the major T cell population in epithelial tissues, play a central role in protective and pathogenic immune responses in the skin. However, the tissue-specific mechanisms that control the innate immune response and the effector functions of GD T cells, especially the cross-talk with commensal organisms, are not very well understood. We hypothesized that the most prevalent skin commensal microorganism, Staphylococcus epidermidis, may play a role in regulating GD T cell-mediated cutaneous responses. We analyzed antimicrobial protein P-2 expression in human skin at a single cell resolution using an amplified fluorescence in situ hybridization approach to detect P-2 mRNA in combination with immunophenotyping. We show that S. epidermidis activates GD T cells and upregulates P-2 in human skin ex vivo in a cell-specific manner. Furthermore, P-2 upregulation following S. epidermidis stimulation correlates with increased ability of skin cells to kill intracellular Staphylococcus aureus. Our findings are the first to reveal that skin commensal bacteria induce P-2 expression, which may be utilized beneficially to modulate host innate immune responses and protect from skin infections.
- Published
- 2020
7. Testing a Way to Keep Staph Infections from Recurring
- Author
-
Jonathan Tobin, María Pardos de la Gándara, Brianna D’Orazio, Suzanne Hower, Roger Vaughan, Joel Corrêa da Rosa, Rhonda Kost, Kimberly Vasquez, Teresa Evering, Chamanara Khalida, Hermínia de Lencastre, Alexander Tomasz, and Barry Coller
- Subjects
Business - Published
- 2020
8. Comparative Effectiveness Study of Home-Based Interventions to Prevent CA-MRSA Infection Recurrence
- Author
-
Jonathan N. Tobin, Roger D. Vaughan, Kimberly S. Vasquez, Rhonda G. Kost, Leidy Johana González, Brianna D’Orazio, Hermínia de Lencastre, Alexander Tomasz, Chamanara Khalida, Suzanne Hower, Barry S. Coller, Jessica Ramachandran, Teresa H. Evering, and Maria Pardos de la Gandara
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,practice-based research network (PBRN) ,media_common.quotation_subject ,Mupirocin ,RM1-950 ,MRSA infection ,Biochemistry ,Microbiology ,Article ,law.invention ,chemistry.chemical_compound ,Antibiotic resistance ,Randomized controlled trial ,Quality of life ,Hygiene ,law ,Internal medicine ,medicine ,Pharmacology (medical) ,skin and soft tissue infection (SSTI) ,General Pharmacology, Toxicology and Pharmaceutics ,media_common ,methicillin-resistant Staphylococcus aureus (MRSA) ,randomized clinical trial (RCT) ,business.industry ,Transmission (medicine) ,Home based interventions ,Chlorhexidine ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,Infectious Diseases ,antibiotic-resistance ,community-based participatory research (CBPR) ,chemistry ,Cohort ,Therapeutics. Pharmacology ,business ,medicine.drug - Abstract
Recurrent skin and soft tissue infections (SSTI) caused by Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) or Methicillin-Sensitive Staphylococcus aureus (CA-MSSA) present treatment challenges. This community-based trial examined the effectiveness of an evidence-based intervention (CDC Guidelines, topical decolonization, surface decontamination) to reduce SSTI recurrence, mitigate household contamination/transmission, and improve patient-reported outcomes. Participants (n = 186) were individuals with confirmed MRSA(+)/MSSA(+) SSTIs and their household members. During home visits, Community Health Workers/Promotoras provided hygiene instructions, a five-day supply of nasal mupirocin, chlorhexidine for body cleansing, and household disinfecting wipes (Experimental, EXP) or Usual Care Control (UC CON) pamphlets. Primary outcome was six-month SSTI recurrence from electronic health records (EHR). Home visits (months 0, 3) and telephone assessments (months 0, 1, 6) collected self-report data. Index patients and participating household members provided surveillance culture swabs. Secondary outcomes included household surface contamination, household member colonization and transmission, quality of life, and satisfaction with care. There were no significant differences in SSTI recurrence between EXP and UC in the intent-to-treat cohort (n = 186) or the enrolled cohort (n = 119). EXP participants showed reduced but non-significant colonization rates. EXP and UC did not differ in household member transmission, contaminated surfaces, or patient-reported outcomes. This intervention did not reduce clinician-reported MRSA/MSSA SSTI recurrence. Taken together with other recent studies that employed more intensive decolonization protocols, it is possible that a promotora-delivered intervention instructing treatment for a longer or repetitive duration may be effective and should be examined by future studies.
- Published
- 2020
9. Mutually constructive roles of Ail and LPS in Yersinia pestis serum survival
- Author
-
Francesca M. Marassi, Andrey P. Anisimov, Suzanne Hower, Chandan Singh, Sara Schesser Bartra, Rima Z. Shaikhutdinova, Sergey Ivanov, Lynn M. Fujimoto, Hwayoung Lee, Wonpil Im, Yong Yao, Gregory V. Plano, and Ye Tian
- Subjects
Lipopolysaccharides ,Lipopolysaccharide ,Protein Conformation ,Virulence Factors ,Yersinia pestis ,Amino Acid Motifs ,Virulence ,Microbial Sensitivity Tests ,Molecular Dynamics Simulation ,Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,Antibiotic resistance ,Drug Resistance, Bacterial ,Humans ,Molecular Biology ,Research Articles ,030304 developmental biology ,0303 health sciences ,Plague ,Innate immune system ,biology ,030306 microbiology ,biology.organism_classification ,Anti-Bacterial Agents ,chemistry ,Mutation ,Cell envelope ,Bacterial outer membrane ,Bacteria ,Bacterial Outer Membrane Proteins ,Protein Binding - Abstract
The outer membrane is a key virulence determinant of gram‐negative bacteria. In Yersinia pestis, the deadly agent that causes plague, the protein Ail and lipopolysaccharide (LPS)(6) enhance lethality by promoting resistance to human innate immunity and antibiotics, enabling bacteria to proliferate in the human host. Their functions are highly coordinated. Here we describe how they cooperate to promote pathogenesis. Using a multidisciplinary approach, we identify mutually constructive interactions between Ail and LPS that produce an extended conformation of Ail at the membrane surface, cause thickening and rigidification of the LPS membrane, and collectively promote Y. pestis survival in human serum, antibiotic resistance, and cell envelope integrity. The results highlight the importance of the Ail–LPS assembly as an organized whole, rather than its individual components, and provide a handle for targeting Y. pestis pathogenesis.
- Published
- 2020
10. LPS modifications and AvrA activity of Salmonella enterica serovar Typhimurium are required to prevent Perforin-2 expression by infected fibroblasts and intestinal epithelial cells
- Author
-
Suzanne Hower, Eckhard R. Podack, Sara Schesser Bartra, Noula Shembade, Gregory V. Plano, Ryan McCormack, and Patricia Alonso
- Subjects
Lipopolysaccharides ,Salmonella typhimurium ,0301 basic medicine ,Salmonella ,Cell type ,030106 microbiology ,chemical and pharmacologic phenomena ,Serogroup ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,Bacterial Proteins ,medicine ,Secretion ,MACPF ,biology ,Perforin ,Effector ,Epithelial Cells ,hemic and immune systems ,Fibroblasts ,biology.organism_classification ,030104 developmental biology ,Infectious Diseases ,Salmonella enterica ,biology.protein ,TLR4 - Abstract
Cellular Perforin-2 (MPEG1) is a pore-forming MACPF family protein that plays a critical role in the defense against bacterial pathogens. Macrophages, neutrophils, and several other cell types that are part of the front line of innate defenses constitutively express high levels of Perforin-2; whereas, most other cell types must be induced to express Perforin-2 by interferons (α, β and γ) and/or PAMPs such as LPS. In this study, we demonstrate that many bacterial pathogens can limit the expression of Perforin-2 in cells normally inducible for Perforin-2 expression, while ordinarily commensal or non-pathogenic bacteria triggered high levels of Perforin-2 expression in these same cell types. The mechanisms by which pathogens suppress Perforin-2 expression was explored further using Salmonella enterica serovar Typhimurium and cultured MEFs as well as intestinal epithelial cell lines. These studies identified multiple factors required to minimize the expression of Perforin-2 in cell types inducible for Perforin-2 expression. These included the PmrAB and PhoPQ two-component systems, select LPS modification enzymes and the Type III secretion effector protein AvrA.
- Published
- 2021
11. Perforin-2 Permeabilizes the Envelope of Phagocytosed Bacteria
- Author
-
Fangfang Bai, Suzanne Hower, Mathias G. Lichtenheld, Gregory V. Plano, George P. Munson, and Ryan McCormack
- Subjects
Proteases ,Protease ,biology ,Chemistry ,medicine.medical_treatment ,Virulence ,hemic and immune systems ,chemical and pharmacologic phenomena ,Periplasmic space ,biology.organism_classification ,In vitro ,Microbiology ,Perforin ,biology.protein ,medicine ,Cell envelope ,Bacteria - Abstract
Perforin-2, the product of theMPEG1gene, limits the spread and dissemination of bacterial pathogens in vivo. It is highly expressed in murine and human phagocytes, and macrophages lacking Perforin-2 are compromised in their ability to kill phagocytosed bacteria. In this study we usedSalmonella typhimuriumas a model intracellular pathogen to elucidate the mechanism of Perforin-2‘s bactericidal activity. In vitro Perforin-2 was found to facilitate the degradation of antigens contained within the envelope of phagocytosed bacteria. In contrast, degradation of a representative surface antigen was found to be independent of Perforin-2. Consistent with our in vitro results a protease sensitive, periplasmic superoxide disumutase (SodCII) contributed to the virulence ofS. typhimuriumin Perforin-2 knockout but not wild-type mice. In aggregate our studies indicate that Perforin-2 breaches the envelope of phagocytosed bacteria facilitating the delivery of proteases and other antimicrobial effectors to sites within the bacterial envelope.
- Published
- 2018
- Full Text
- View/download PDF
12. Human-Associated Methicillin-Resistant Staphylococcus aureus from a Subtropical Recreational Marine Beach
- Author
-
Samir M. Elmir, Kelly Withum, Anna C. Garza, Christopher D. Sinigalliano, Tomoyuki Shibata, Sampa Mukherjee, M K Davidson, Timothy Cleary, Lora E. Fleming, Maribeth L. Gidley, Lisa R. W. Plano, Jonathan Kish, Jay M. Fleisher, Suzanne Hower, Helena M. Solo-Gabriele, Johnnie A. Davis, John B. Barrett, and Charlene R. Jackson
- Subjects
Methicillin-Resistant Staphylococcus aureus ,Meticillin ,medicine.drug_class ,Bacterial Toxins ,Antibiotics ,Exotoxins ,Soil Science ,Drug resistance ,Biology ,medicine.disease_cause ,Microbiology ,Bacterial Proteins ,Leukocidins ,Drug Resistance, Bacterial ,medicine ,Pulsed-field gel electrophoresis ,Humans ,Seawater ,Ecology, Evolution, Behavior and Systematics ,Ecology ,SCCmec ,Staphylococcal Infections ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,Methicillin-resistant Staphylococcus aureus ,Anti-Bacterial Agents ,Staphylococcus aureus ,Multilocus sequence typing ,Public Facilities ,medicine.drug - Abstract
Reports of Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) detected in marine environments have occurred since the early 1990s. This investigation sought to isolate and characterize S. aureus from marine waters and sand at a subtropical recreational beach, with and without bathers present, in order to investigate possible sources and to identify the risks to bathers of exposure to these organisms. During 40 days over 17 months, 1,001 water and 36 intertidal sand samples were collected by either bathers or investigators at a subtropical recreational beach. Methicillin-sensitive S. aureus (MSSA) and MRSA were isolated and identified using selective growth media and an organism-specific molecular marker. Antimicrobial susceptibility, staphylococcal cassette chromosome mec (SCCmec) type, pulsed-field gel electrophoresis (PFGE) pattern, multi-locus sequence type (MLST), and staphylococcal protein A (spa) type were characterized for all MRSA. S. aureus was isolated from 248 (37 %) bather nearby water samples at a concentration range of
- Published
- 2013
13. Clonally Related Methicillin-Resistant Staphylococcus aureus Isolated from Short-Finned Pilot Whales (Globicephala macrorhynchus), Human Volunteers, and a Bayfront Cetacean Rehabilitation Facility
- Author
-
Maribeth L. Gidley, Frank E. Johnson, John B. Barrett, Matthew C. Phillips, Lisa Johns, Charlene R. Jackson, Christopher D. Sinigalliano, Suzanne Hower, Olufunmilola Adebanjo, Lisa R. W. Plano, Adrienne S. Dameron, M K Davidson, Manuel A. Tamargo, Ruth Y. Ewing, Norma C. Salazar, Micah Brodsky, Sampa Mukherjee, and Johnnie A. Davis
- Subjects
Methicillin-Resistant Staphylococcus aureus ,Volunteers ,Veterinary medicine ,Soil Science ,medicine.disease_cause ,Microbiology ,Marine mammal ,biology.animal ,Pulsed-field gel electrophoresis ,medicine ,Animals ,Humans ,Typing ,Ecology, Evolution, Behavior and Systematics ,Fin Whale ,Ecology ,biology ,Whale ,Staphylococcal Infections ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,Methicillin-resistant Staphylococcus aureus ,Anti-Bacterial Agents ,Staphylococcus aureus ,Florida ,Multilocus sequence typing ,Cetacea ,Globicephala macrorhynchus - Abstract
In May of 2011, a live mass stranding of 26 short-finned pilot whales (Globicephala macrorhynchus) occurred in the lower Florida Keys. Five surviving whales were transferred from the original stranding site to a nearby marine mammal rehabilitation facility where they were constantly attended to by a team of volunteers. Bacteria cultured during the routine clinical care of the whales and necropsy of a deceased whale included methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA). In order to investigate potential sources or reservoirs of MSSA and MRSA, samples were obtained from human volunteers, whales, seawater, and sand from multiple sites at the facility, nearby recreational beaches, and a canal. Samples were collected on 3 days. The second collection day was 2 weeks after the first, and the third collection day was 2 months after the last animal was removed from the facility. MRSA and MSSA were isolated on each day from the facility when animals and volunteers were present. MSSA was found at an adjacent beach on all three collection days. Isolates were characterized by utilizing a combination of quantitative real-time PCR to determine the presence of mecA and genes associated with virulence, staphylococcal protein A typing, staphylococcal cassette chromosome mec typing, multilocus sequence typing, and pulsed field gel electrophoresis (PFGE). Using these methods, clonally related MRSA were isolated from multiple environmental locations as well as from humans and animals. Non-identical but genetically similar MSSA and MRSA were also identified from distinct sources within this sample pool. PFGE indicated that the majority of MRSA isolates were clonally related to the prototype human strain USA300. These studies support the notion that S. aureus may be shed into an environment by humans or pilot whales and subsequently colonize or infect exposed new hosts.
- Published
- 2013
14. Domain Analyses Reveal That Chlamydia trachomatis CT694 Protein Belongs to the Membrane-localized Family of Type III Effector Proteins
- Author
-
Kenneth A. Fields, Holly D. Bullock, and Suzanne Hower
- Subjects
Vesicle-associated membrane protein 8 ,Chlamydia trachomatis ,Biology ,urologic and male genital diseases ,medicine.disease_cause ,Microbiology ,Biochemistry ,Type three secretion system ,Cell membrane ,Protein structure ,Bacterial Proteins ,Salmonella ,Pseudomonas ,Stress Fibers ,medicine ,Humans ,Molecular Biology ,Actin ,Effector ,Cell Membrane ,Membrane Proteins ,Cell Biology ,Chlamydia Infections ,Yersinia ,Neoplasm Proteins ,Protein Structure, Tertiary ,Cell biology ,medicine.anatomical_structure ,Membrane protein ,HeLa Cells - Abstract
The Chlamydia trachomatis type three-secreted effector protein CT694 is expressed during late-cycle development yet is secreted by infectious particles during the invasion process. We have previously described the presence of at least two functional domains within CT694. CT694 was found to interact with the human protein Ahnak through a C-terminal domain and affect formation of host-cell actin stress fibers. Immunolocalization analyses of ectopically expressed pEGFP-CT694 also revealed plasma membrane localization for CT694 that was independent of Ahnak binding. Here we provide evidence that CT694 contains multiple functional domains. Plasma membrane localization and CT694-induced alterations in host cell morphology are dependent on an N-terminal domain. We demonstrate that membrane association of CT694 is dependent on a domain resembling a membrane localization domain (MLD) found in anti-host proteins from Yersinia, Pseudomonas, and Salmonella spp. This domain is necessary and sufficient for localization and morphology changes but is not required for Ahnak binding. Further, the CT694 MLD is able to complement ExoS ΔMLD when ectopically expressed. Taken together, our data indicate that CT694 is a multidomain protein with the potential to modulate multiple host cell processes.
- Published
- 2012
15. Treatment of Chlamydia trachomatis with a small molecule inhibitor of the Yersinia type III secretion system disrupts progression of the chlamydial developmental cycle
- Author
-
K. A. Fields, B. Chellas-Géry, H. J. Betts, Suzanne Hower, C. N. Linton, and Katerina Wolf
- Subjects
Population ,Chlamydiae ,Chlamydia trachomatis ,Yersinia ,medicine.disease_cause ,Microbiology ,Article ,Type three secretion system ,Bacterial Proteins ,medicine ,Humans ,Chlamydiaceae ,Secretion ,education ,Molecular Biology ,Cells, Cultured ,education.field_of_study ,biology ,Membrane Proteins ,Biological Transport ,Chaperonin 60 ,bacterial infections and mycoses ,biology.organism_classification ,Coxiella burnetii ,Hydrazines ,bacteria - Abstract
The obligate intracellular bacterium Chlamydia trachomatis possesses a biphasic developmental cycle that is manifested by differentiation of infectious, metabolically inert elementary bodies (EBs) to larger, metabolically active reticulate bodies (RBs). The cycle is completed by asynchronous differentiation of dividing RBs back to a population of dormant EBs that can initiate further rounds of infection upon lysis of the host cell. Chlamydiae express a type III secretion system (T3SS) which is presumably employed to establish and maintain the permissive intracellular niche by secretion of anti-host proteins. We hypothesize that T3SS activity is essential for chlamydial development and pathogenesis. However, the lack of a genetic system has confounded efforts to establish any role of the T3SS. We therefore employed the small molecule Yersinia T3SS inhibitor ′N′-(3,5-dibromo-2-hydroxybenzylidene)-4-nitrobenzohydrazide, designated compound 1 (C1), to examine the inter-dependence of the chlamydial T3SS and development. C1-treatment inhibited C. trachomatis but not T4SS-expressing Coxiella burnetii development in a dose-dependent manner. Although chlamydiae remained viable and metabolically active, they failed to divide significantly and RB to EB differentiation was inhibited. These effects occurred in the absence of host cell cytotoxicity and were reversible by washing out C1. We further demonstrate that secretion of T3S substrates is perturbed in C1-treated chlamydial cultures. We have therefore provided evidence that C1 can inhibit C. trachomatis development and T3SS activity and present a model in which progression of the C. trachomatis developmental cycle requires a fully functional T3SS.
- Published
- 2006
16. Keratinocytes produce IL-6 in response to desmoglein 1 cleavage by Staphylococcus aureus exfoliative toxin A
- Author
-
Lisa R. W. Plano, Juan Chen, Richard V. Snyder, Irena Pastar, Cleo E. Rolle, Roberto Perez, Franco Ferracci, Marjana Tomic-Canic, Suzanne Hower, and Tatiana C. Cardenas
- Subjects
Keratinocytes ,Methicillin-Resistant Staphylococcus aureus ,Staphylococcus aureus ,Virulence Factors ,Immunology ,Leukocidin ,Virulence ,Biology ,medicine.disease_cause ,Microbiology ,Cell Line ,Immune system ,medicine ,Leukocytes ,Animals ,Humans ,Staphylococcus aureus delta toxin ,Pathogen ,Toxin ,Interleukin-6 ,Desmoglein 1 ,biochemical phenomena, metabolism, and nutrition ,respiratory system ,bacterial infections and mycoses ,Staphylococcal scalded skin syndrome ,medicine.disease ,Exfoliatins ,Proteolysis ,Staphylococcal Skin Infections ,Epidermis ,circulatory and respiratory physiology - Abstract
Many skin infections are caused by Staphylococcus aureus, a bacterial pathogen that produces virulence factors associated with these conditions such as exfoliative toxins A and B (ETA, ETB) and the leukotoxin Panton–Valentine leukocidin (PVL). Herein, we examine the potential of skin-infecting S. aureus to produce virulence factors and their impact on the local immune response. Toxin gene profiles were generated from 188 S. aureus isolated as single infecting organisms from skin lesions and demonstrated a higher potential to express ETA, ETB, and PVL than community isolates (p
- Published
- 2013
17. Correlation of Twenty Virulence Genes of Staphylococcus aureus with Severity of Atopic Dermatitis in Children as Compared to Healthy Individuals
- Author
-
Jan Izakovic, Lisa R. W. Plano, Suzanne Hower, Stephen C. Davis, and Anja Jochmann
- Subjects
SCCmec ,Virulence ,Atopic dermatitis ,Biology ,medicine.disease_cause ,medicine.disease ,Virulence factor ,Microbiology ,Staphylococcus aureus ,Genotype ,Immunology ,medicine ,MSCRAMM ,Staphylococcus - Abstract
Principles: Patients with Atopic Dermatitis (AD) have a higher susceptibility for colonization and infection with Staphylococcus aureus. Virulence factors of S. aureus may modulate the host immune response and affect the clinical course of infection. Methods: Bacterial cultures were obtained from AD patients and uninfected controls. PCR and DNA sequence analysis were used to determine microbial surface components recognizing adhesive matrix molecules (MSCRAMM) patterns, staphylococcus protein A (spa) types, and the presence of genes for 20 virulence factors and for methicillin resistance (mecA). Virulence factor gene patterns from AD associated S. aureus were compared with gene patterns from the control group, as well as with S. aureus previously obtained from infected skin lesions not associated with AD. Results: The gene encoding chemotaxis inhibiting protein (chp) was found more frequently in S. aureus isolated from the uninfected control group (p=0.0003). Isolates of AD patients were more likely to carry the gene sea (p=0.0327), which encodes for an enterotoxin known to act as a superantigen. Prevalence of eta, etb and chp were significantly associated with organisms isolated from non-AD infected lesions (eta: p=0.0003, etb: p=0.0001, chp: p=0.012) There was no difference in the prevalence of any MSCRAMM gene pattern or 19 additional virulence factors genes analyzed, and none were associated with severity of the AD lesions. MRSA SCCmec type IVa made up approximately 8% of both AD and control isolates. Conclusions: The genotypes of S. aureus strains colonizing AD patients do not differ significantly from the genotypes of strains colonizing healthy individuals. Isolates infecting patients without AD express significantly more eta and etb and therefore seem to be more virulent to overcome the intact skin barrier.
- Published
- 2013
18. Evidence that CT694 is a novel Chlamydia trachomatis T3S substrate capable of functioning during invasion or early cycle development
- Author
-
Suzanne Hower, K. A. Fields, and Katerina Wolf
- Subjects
Chlamydia trachomatis ,Vacuole ,Biology ,Yersinia ,medicine.disease_cause ,Microbiology ,Article ,Bacterial Proteins ,Species Specificity ,medicine ,Humans ,Secretion ,Molecular Biology ,Regulation of gene expression ,Effector ,Intracellular parasite ,Membrane Proteins ,Gene Expression Regulation, Bacterial ,Chlamydia Infections ,biology.organism_classification ,Cell biology ,Neoplasm Proteins ,Interaction with host ,Host-Pathogen Interactions ,HeLa Cells - Abstract
Chlamydia trachomatis is an obligate intracellular parasite, occupies a membrane-bound vacuole throughout development and is capable of manipulating the eukaryotic host by translocating effector molecules via a type III secretion system (T3SS). The infectious chlamydial elementary body (EB) is metabolically inactive yet possesses a functional T3S apparatus capable of translocating effector proteins into the host cell to facilitate invasion and other early cycle events. We present evidence here that the C. trachomatis protein CT694 represents an early cycle-associated effector protein. CT694 is secreted by the Yersinia T3SS and immunodetection studies of infected HeLa cultures indicate that CT694-specific signal accumulates directly adjacent to, but not completely overlapping with EBs during invasion. Yeast two-hybrid analyses revealed an interaction of CT694 with the repeat region and C-terminus of human AHNAK. Immunolocalization studies of CT694 ectopically expressed in HeLa cells were consistent with an interaction with endogenous AHNAK. Additionally, expression of CT694 in HeLa cells resulted in alterations in the detection of stress fibres that correlated with the ability of CT694 to interact with AHNAK. These data indicate that CT694 is a novel T3S-dependent substrate unique to C. trachomatis, and that its interaction with host proteins such as AHNAK may be important for aspects of invasion or development particular to this species.
- Published
- 2009
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.