Pathogenic Microbiology Commons^™

Listeria Adhesion Protein Orchestrates Caveolae-Mediated Apical Junctional Remodeling Of Epithelial Barrier For Listeria Monocytogenes Translocation, Rishi Drolia, Donald B. Bryant, Shivendra Tenguria, Zuri A. Jules-Culver, Jessie Thind, Breanna Amelunke, Donqi Liu, Nicholas L. F. Gallina, Krishna K. Mishra, Manalee Samaddar, Manoj R. Sawale, Dharmendra K. Mishra, Abigail D. Cox, Arun K. Bhunia

Biological Sciences Faculty Publications

The cellular junctional architecture remodeling by Listeria adhesion protein-heat shock protein 60 (LAP-Hsp60) interaction for Listeria monocytogenes (Lm) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate that Lm crosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (lap− or ΔinlA) or double (lap−ΔinlA) mutant strains show significant defects. LAP promotes Lm translocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA facilitates …

Host-Defense Piscidin Peptides As Antibiotic Adjuvants Against Clostridioides Difficile, Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu²⁺ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of …

Marineepi: A Gui-Based Matlab Toolbox To Simulate Marine Pathogen Transmission, Gorka Bidegain, Tal Ben-Horin, Eric N. Powell, John M. Klinck, Eileen E. Hofmann

CCPO Publications

The Graphical User Interface (GUI) MarineEpi is presented as a Matlab toolbox for easily (i) constructing disease transmission models for different marine host-pathogen systems, (ii) running simulations by specifying initial conditions and model parameters, and (iii) interpreting the resulting time series of the host and pathogen population dynamics. MarineEpi users can generate models for systems in which pathogen transmission occurs through contact with infected individuals (SI), contact with dead infected individuals (SID), contact with environmental pathogens released by infected individuals (SIP), and contact with environmental pathogens released by dead infected individuals (SIPD). MarineEpi is a freely available GUI that provides …

Multipatch Stochastic Epidemic Model For The Dynamics Of A Tick-Borne Disease, Milliward Maliyoni, Holly D. Gaff, Keshlan S. Govinder, Faraimunashe Chirove

Biological Sciences Faculty Publications

Spatial heterogeneity and migration of hosts and ticks have an impact on the spread, extinction and persistence of tick-borne diseases. In this paper, we investigate the impact of between-patch migration of white-tailed deer and lone star ticks on the dynamics of a tick-borne disease with regard to disease extinction and persistence using a system of Itô stochastic differential equations model. It is shown that the disease-free equilibrium exists and is unique. The general formula for computing the basic reproduction number for all patches is derived. We show that for patches in isolation, the basic reproduction number is equal to the …

Frankenbacteriosis Targeting Interactions Between Pathogen And Symbiont To Control Infection In The Tick Vector, Lorena Mazuecos, Pilar Alberdi, Angélica Hernández-Jarguín, Marinela Contreras, Margarita Villar, Alejandro Cabezas-Cruz, Ladislav Simo, Almudena González-García, Sandra Díaz-Sánchez, Girish Neelakanta, Sarah I. Bonnet, Erol Fikrig, José De La Fuente

Biological Sciences Faculty Publications

(Summary) Tick microbiota can be targeted for the control of tick-borne diseases such as human granulocytic anaplasmosis (HGA) caused by model pathogen, Anaplasma phagocytophilum. Frankenbacteriosis is inspired by Frankenstein and defined here as paratransgenesis of tick symbiotic/commensal bacteria to mimic and compete with tick-borne pathogens. Interactions between A. phagocytophilum and symbiotic Sphingomonas identified by metaproteomics analysis in Ixodes scapularis midgut showed competition between both bacteria. Consequently, Sphingomonas was selected for frankenbacteriosis for the control of A. phagocytophilum infection and transmission. The results showed that Franken Sphingomonas producing A. phagocytophilum major surface protein 4 (MSP4) mimic pathogen and reduce infection …

Expanding Our Grasp Of Two-Component Signaling In Clostridioides Difficile, Orlando Berumen Alvarez, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The intestinal pathogen Clostridioides difficile encodes roughly 50 TCS, but very few have been characterized in terms of their activating signals or their regulatory roles. A. G. Pannullo, B. R. Zbylicki, and C. D. Ellermeier (J Bacteriol 205:e00164-23, 2023, https://doi.org/10.1128/jb.00164-23) have identified both for the novel C. difficile TCD DraRS. DraRS responds to antibiotics that target lipid-II molecules in the bacterial cell envelope, and regulates the production of a novel glycolipid necessary for bacitracin and daptomycin resistance in C. difficile.

Investigating Public Support For Biosecurity Measures To Mitigate Pathogen Transmission Through The Herpetological Trade, Elizabeth F. Pienaar, Diane J. Episcopio-Sturgeon, Zachary T. Steele

Biological Sciences Faculty Publications

The expanding global trade in herpetofauna has contributed to new infectious disease dynamics and pathways that allow for the rapid spread of pathogens geographically. Improved biosecurity is needed to mitigate adverse biodiversity, economic and human health impacts associated with pathogen transmission through the herpetological trade. However, general lack of knowledge of the pathogen transmission risks associated with the global trade in herpetofauna and public opposition to biosecurity measures are critical obstacles to successfully preventing pathogen transmission. In 2019 we administered a survey to 2,007 members of the public in the United States of America to ascertain their support for interventions …

Repression Of Tick Microrna-133 Induces Organic Anion Transporting Polypeptide Expression Critical For Anaplasma Phagocytophilumsurvival In The Vector And Transmission To The Vertebrate Host, Ellango Ramasamy, Vikas Taank, John F. Anderson, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

The microRNAs (miRNAs) are important regulators of gene expression. In this study, we provide evidence for the first time to show that rickettsial pathogen Anaplasma phagocytophilum infection results in the down-regulation of tick microRNA-133 (miR-133), to induce Ixodes scapularis organic anion transporting polypeptide (isoatp4056) gene expression critical for this bacterial survival in the vector and for its transmission to the vertebrate host. Transfection studies with recombinant constructs containing transcriptional fusions confirmed binding of miR-133 to isoatp4056 mRNA. Treatment with miR-133 inhibitor resulted in increased bacterial burden and isoatp4056 expression in ticks and tick cells. In contrast, treatment with …

Characterization Of Tick Organic Anion Transporting Polypeptides (Oatps) Upon Bacterial And Viral Infections, Vikas Taank, Wenshou Zhou, Xuran Zhuang, John F. Anderson, Utpal Pal, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Background: Ixodes scapularis organic anion transporting polypeptides (OATPs) play important roles in tickrickettsial pathogen interactions. In this report, we characterized the role of these conserved molecules in ticks infected with either Lyme disease agent Borrelia burgdorferi or tick-borne Langat virus (LGTV), a pathogen closely related to tick-borne encephalitis virus (TBEV).

Results: Quantitative real-time polymerase chain reaction analysis revealed no significant changes in oatps gene expression upon infection with B. burgdorferi in unfed ticks. Synchronous infection of unfed nymphal ticks with LGTV in vitro revealed no significant changes in oatps gene expression. However, expression of specific oatps was significantly downregulated upon …

Arthropod Transcriptional Activator Protein-1 (Ap-1) Aids Tick-Rickettsial Pathogen Survival In The Cold, Supreet Khanal, Vikas Taank, John F. Anderson, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ixodes scapularis ticks transmit several pathogens to humans including rickettsial bacterium, Anaplasma phagocytophilum. Here, we report that A. phagocytophilum uses tick transcriptional activator protein-1 (AP-1) as a molecular switch in the regulation of arthropod antifreeze gene, iafgp. RNAi-mediated silencing of ap-1 expression significantly affected iafgp gene expression and A. phagocytophilum burden in ticks upon acquisition from the murine host. Gel shift assays provide evidence that both the bacterium and AP-1 influences iafgp promoter and expression. The luciferase assays revealed that a region of approximately 700 bp upstream of the antifreeze gene is sufficient for AP-1 binding to promote …

Size-Dependent Inhibitory Effects Of Antibiotic Drug Nanocarriers Against Pseudomonas Aeruginosa, Feng Ding, Preeyaporn Songkiatisak, Pavan Kumar Cherukuri, Tao Huang, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Multidrug membrane transporters (efflux pumps) are responsible for multidrug resistance (MDR) and the low efficacy of therapeutic drugs. Noble metal nanoparticles (NPs) possess a high surface-area-to-volume ratio and size-dependent plasmonic optical properties, enabling them to serve both as imaging probes to study sized-dependent MDR and as potential drug carriers to circumvent MDR and enhance therapeutic efficacy. To this end, in this study, we synthesized three different sizes of silver nanoparticles (Ag NPs), 2.4 ± 0.7, 13.0 ± 3.1, and 92.6 ± 4.4 nm, functionalized their surface with a monolayer of 11-amino-1-undecanethiol (AUT), and covalently conjugated them with antibiotics (ofloxacin, Oflx) …

Human Rickettsial Pathogen Modulates Arthropod Organic Anion Transporting Polypeptide And Tryptophan Pathway For Its Survival In Ticks, Vikas Taank, Shovan Dutta, Amrita Dasgupta, Durland Fish, John F. Anderson, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

The black-legged tick Ixodes scapularis transmits the human anaplasmosis agent, Anaplasma phagocytophilum. In this study, we show that A. phagocytophilum specifically up-regulates I. scapularis organic anion transporting polypeptide, isoatp4056 and kynurenine amino transferase (kat), a gene involved in the production of tryptophan metabolite xanthurenic acid (XA), for its survival in ticks. RNAi analysis revealed that knockdown of isoatp4056 expression had no effect on A. phagocytophilum acquisition from the murine host but affected the bacterial survival in tick cells. Knockdown of the expression of kat mRNA alone or in combination with isoatp4056 mRNA significantly affected A. phagocytophilum survival …

Ticks Elicit Variable Fibrinogenolytic Activities Upon Feeding On Hosts With Different Immune Backgrounds, Ashish Vora, Vikas Taank, John F. Anderson, Durland Fish, Daniel E. Sonenshine, John D. Catravas, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ticks secrete several anti-hemostatic factors in their saliva to suppress the host innate and acquired immune defenses against infestations. Using Ixodes scapularis ticks and age-matched mice purchased from two independent commercial vendors with two different immune backgrounds as a model, we show that ticks fed on immunodeficient animals demonstrate decreased fibrinogenolytic activity in comparison to ticks fed on immunocompetent animals. Reduced levels of D-dimer (fibrin degradation product) were evident in ticks fed on immunodeficient animals in comparison to ticks fed on immunocompetent animals. Increased engorgement weights were noted for ticks fed on immunodeficient animals in comparison to ticks fed on …

Neurotrophic Factors Ngf, Gdnf And Ntn Selectively Modulate Hsv1 And Hsv2 Lytic Infection And Reactivation In Primary Adult Sensory And Autonomic Neurons, Andy Y. Yanez, Telvin Harrell, Heather J. Sriranganathan, Angela M. Ives, Andrea S. Bertke

Medical Diagnostics & Translational Sciences Faculty Publications

Herpes simplex viruses (HSV1 and HSV2) establish latency in peripheral ganglia after ocular or genital infection, and can reactivate to produce different patterns and frequencies of recurrent disease. Previous studies showed that nerve growth factor (NGF) maintains HSV1 latency in embryonic sympathetic and sensory neurons. However, adult sensory neurons are no longer dependent on NGF for survival, some populations cease expression of NGF receptors postnatally, and the viruses preferentially establish latency in different populations of sensory neurons responsive to other neurotrophic factors (NTFs). Thus, NGF may not maintain latency in adult sensory neurons. To identify NTFs important for maintaining HSV1 …

Anaplasma Marginale Actively Modulates Vacuolar Maturation During Intracellular Infection Of Its Tick Vector, Dermacentor Andersoni, Foregivemore Magunda, Chelsea Wright Thompson, David A. Schneider, Susan M. Noh

Biological Sciences Faculty Publications

ABSTRACT Tick-borne transmission of bacterial pathogens in the order Rickettsiales is responsible for diverse infectious diseases, many of them severe, in humans and animals. Transmission dynamics differ among these pathogens and are reflected in the pathogen-vector interaction. Anaplasma marginale has been shown to establish and maintain infectivity within Dermacentor spp. for weeks to months while escaping the complex network of vacuolar peptidases that are responsible for digestion ofthe tick blood meal. How this prolonged maintenance of infectivity in a potentially hostile environment is achieved has been unknown. Using the natural vector Dermacentor andersoni, we demonstrated that A. marginale …

Donor Platelet Plasma Components Inactivate Sensitive And Multidrug Resistant Acinetobacter Baumannii Isolates, Chelsea M. Edelblute, Olga N. Pakhomova, Fanying Li, Barbara Y. Hargrave, Loree C. Heller

Bioelectrics Publications

Acinetobacter baumannii is an environmentally resilient healthcare-associated opportunistic pathogen responsible for infections at many body sites. In the last 10 years, clinical strains resistant to many or all commonly used antibiotics have emerged globally. With few antimicrobial agents in the pharmaceutical pipeline, new and alternative agents are essential. Platelets secrete a large number of proteins, including proteins with antimicrobial activity. In a previous study, we demonstrated that donor platelet supernatants and plasma significantly inhibited the growth of a reference strain of A. baumannii in broth and on skin. This inhibition appeared to be unrelated to the platelet activation state. In …

The Toxavapa Toxin-Antitoxin Locus Contributes To The Survival Of Nontypeable Haemophilus Influenzae During Infection, Dabin Ren, Alexis A. Kordis, Daniel E. Sonenshine, Dayle A. Daines

Biological Sciences Faculty Publications

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that is a common cause of acute and recurrent mucosal infections. One uncharacterized NTHi toxin-antitoxin (TA) module, NTHI1912-1913, is a host inhibition of growth (higBA) homologue. We hypothesized that this locus, which we designated toxAvapA, contributed to NTHi survival during infection. We deleted toxAvapA and determined that growth of the mutant in defined media was not different from the parent strain. We tested the mutant for persistence during long-term in vitro co-culture with primary human respiratory tissues, which revealed that the DeltatoxAvapA mutant was attenuated for survival. We then …