Microbiology Commons^™

Antimicrobial Efficacy Of Natural Bioactive Compounds And High Pressure Processing Against Potential Pathogens In Infant Foods, Hayriye Cetin-Karaca

Theses and Dissertations--Animal and Food Sciences

This study investigated the antimicrobial efficacy of bioactive plant compounds along with high pressure processing (HPP) against pathogens Bacillus cereus and Cronobacter sakazakii in infant formula and infant rice cereal. The influence of these applications on antimicrobial activity, shelf-life and sensory attributes of infant foods were examined.

Trans-cinnamaldehyde (TC), (-)-Epigallocatechin gallate (EGCG) and [10]-Gingerol (GI) were incorporated (0.05%) in infant rice cereal reconstituted with infant formula. The cereal was inoculated with either B. cereus (ATCC 14579) or B. cereus spores (10⁷-10⁸ log CFU g^-1). All the samples were stored at 7, 23 or 37°C for …

A Nuclear Fraction Of Turnip Crinkle Virus Capsid Protein Is Important For Elicitation Of The Host Resistance Response, Sung-Hwan Kang, Feng Qu, Thomas J. Morris

Nebraska Center for Virology: Faculty Publications

The N-terminal 25 amino acids (AAs) of turnip crinkle virus (TCV) capsid protein (CP) are recognized by the resistance protein HRT to trigger a hypersensitive response (HR) and systemic resistance to TCV infection. This same region of TCV CP also contains a motif that interacts with the transcription factor TIP, as well as a nuclear localization signal (NLS). However, it is not yet known whether nuclear localization of TCV CP is needed for the induction of HRT-mediated HR and resistance. Here we present new evidence suggesting a tight correlation between nuclear inclusions formed by CP and the manifestation of HR. …

A Novel Codon-Optimized Siv Gag-Pol Immunogen For Genebased Vaccination, Catherine M. Crosby, Eric A. Weaver, Reeti Khare, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag-pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells …

Inhibition Of Shp2 Suppresses Mutant Egfr-Induced Lung Tumors In Transgenic Mouse Model Of Lung Adenocarcinoma, Valentina E. Schneeberger, Yuan Ren, Noreen Luetteke, Qingling Huang, Liwei Chen, Harshani R. Lawrence, Nicholas J. Lawrence, Eric B. Haura, John M. Koomen, Domenico Coppola, Jie Wu

Molecular Biosciences Faculty Publications

Epidermal growth factor receptor (EGFR) mutants drive lung tumorigenesis and are targeted for therapy. However, resistance to EGFR inhibitors has been observed, in which the mutant EGFR remains active. Thus, it is important to uncover mediators of EGFR mutant-driven lung tumors to develop new treatment strategies. The protein tyrosine phosphatase (PTP) Shp2 mediates EGF signaling. Nevertheless, it is unclear if Shp2 is activated by oncogenic EGFR mutants in lung carcinoma or if inhibiting the Shp2 PTP activity can suppress EGFR mutant-induced lung adenocarcinoma. Here, we generated transgenic mice containing a doxycycline (Dox)-inducible PTP-defective Shp2 mutant (tetO-Shp2CSDA). Using the rat Clara …

The Νsaα Specific Lipoprotein Like Cluster (Lpl) Of S. Aureus Usa300 Contributes To Immune Stimulation And Invasion In Human Cells, Minh Thu Nguyen, Beatrice Kraft, Wenqi Yu, Dogan Doruk Demicrioglu, Tobias Hertlein, Marc Burian, Mathias Schmaler, Klaus Boller, Isabelle Bekeredjian-Ding, Knut Ohlsen, Birgit Schittek, Friedrich Götz

Molecular Biosciences Faculty Publications

All Staphylococcus aureus genomes contain a genomic island, which is termed νSaα and characterized by two clusters of tandem repeat sequences, i.e. the exotoxin (set) and 'lipoprotein-like' genes (lpl). Based on their structural similarities the νSaα islands have been classified as type I to IV. The genomes of highly pathogenic and particularly epidemic S. aureus strains (USA300, N315, Mu50, NCTC8325, Newman, COL, JH1 or JH9) belonging to the clonal complexes CC5 and CC8 bear a type I νSaα island. Since the contribution of the lpl gene cluster encoded in the νSaα island to virulence is unclear to date, we deleted …

Candida Albicans Quorum Sensing Molecules Stimulate Mouse Macrophage Migration, Jessica C. Hargarten, Tyler C. Moore, Thomas M. Petro, Kenneth W. Nickerson, Audrey L. Atkin

Kenneth Nickerson Papers

The polymorphic commensal fungus Candida albicans causes life-threatening disease via bloodstream and intra-abdominal infections in immunocompromised and transplant patients. Although host immune evasion is a common strategy used by successful human fungal pathogens, C. albicans provokes recognition by host immune cells less capable of destroying it. To accomplish this, C. albicans white cells secrete a low-molecular-weight chemoattractive stimulant(s) of macrophages, a phagocyte that they are able to survive within and eventually escape from. C. albicans opaque cells do not secrete this chemoattractive stimulant( s). We report here a physiological mechanism that contributes to the differences in the interaction of C. …

Regulation Of Vldl Trafficking By Orp 10, Philip A. Wessels

HIM 1990-2015

Of the challenges facing the improvement of human health, none has taken the forefront quite like the endeavor to discover novel treatments for heart disease. As heart disease has now become the leading cause of death throughout the world [1], the medical community has made incredible strides in the mission to treat atherosclerosis which is the major contributor to heart disease. Very Low Density Lipoproteins (VLDL) are secreted by the liver and subsequently converted to Low Density Lipoproteins (LDL). Many factors contribute to the narrowing of the arterial walls, however oxidized LDL is the main factor that leads to the …

Application Of Fluorescence In Situ Hybridization For Visualization And Quantification Of Human Gastrointestinal Microbiota, Alexander M. Gordon

Browse all Theses and Dissertations

The microbiota of the human gastrointestinal tract is the focus of current research due to their role in human health and disease. Modern methods characterize the communities of gut microbiota through the use of culture independent techniques. Technologies such as microarrays and next generation sequencing (NGS) determine microbial profiles by analyzing the pool of 16S ribosomal small subunit RNA genes in the community. These techniques operate through the measurement of genomic content rather than through direct analysis of cells. This approach predisposes the methods to discrepancies and bias. In contrast, the use of fluorescence in situ hybridization (FISH) to analyze …

Identification Of The Molecular Mechanisms Governing The Osmotolerance Of The Emerging Gastrointestinal Pathogen Cronobacter Sakazakii, Audrey Feeney

Theses

Cronobacter sakazakii is an organism which has been associated with severe life- threatening diseases in infants and neonates. Mortality rates of up to 80% have been recorded in infants infected with Cronobacter sakazakii. Infants often suffer from septicaemia, necrotising enterocolitis and meningitis as a result of infection. A characteristic feature of the opportunistic foodborne pathogen Cronobacter sakazakii is its ability to survive in extremely arid environments such as powdered infant formula, making it a dangerous opportunistic pathogen of neonates. Herein, we provide a brief overview of the pathogen; clinical manifestations, environmental reservoirs and our current understanding of stress response mechanisms …

Exploiting Bacteriophages And Associated Peptidoglycan Hydrolases With Potential For Biocontrol In Food Related Applications, Lorraine Endersen

Theses

The work presented in this thesis describes the isolation and characterisation of novel bacteriophages, and the subsequent exploitation of their bactericidal properties against two opportunistic food related pathogens, Mycobacterium avium subsp. paratuberculosis (MAP) and Cronobacter sakazakii.

MAP is a proven animal pathogen known to cause Johne’s disease in cattle but has been implicated as a causative agent of Crohn’s disease in humans. Despite the fact that this association has yet to be proven, significant focus has been directed towards evaluating the consequences of consuming milk contaminated with MAP. Accordingly, six mycobacteriophages were isolated and characterised in terms of temperature and …

Characterisation And Applications Of Natural Lactic Acid Bacteria With Emphasis On Weissella Cibaria And Associated Exopolysaccharide, Kieran M. Lynch

Theses

The work presented in this thesis characterises natural cereal-derived lactic acid bacteria and examines their potential application in the dairy fermentation area, with special emphasis on the sourdough isolate, Weissella cibaria MGl and its associated glucan homoexopolysaccharide. This strain is notable for its high-level production of dextran, being termed a “hyper-producef’. Genome sequencing and analysis of a number of IV. cibaria strains was performed in the context of available genomic data for other Weissella species, with special focus on the metabolic traits of W. cibaria MGl, and the results represent the first study to explore members of the Weissella genus …

Increasing The Nutritional Value Of Canola Meal Via Fungal Bioprocessing, Jason R. Croat

Electronic Theses and Dissertations

The main limitation of meals from canola and other Brassica spp. is the presence of glucosinolates (GLS), which are anti-nutritional and can even be toxic at high ingestion levels. Furthermore, large amounts of GLS can reduce palatability for livestock and thus reduce intake and growth rates. For this reason canola was bred to contain lower levels of GLS (<30 >μmol/g) and erucic acid (< 2%). However, feed inclusion rates are still limited to ~30%, and this reduces the value of canola meal. The goal of this thesis was to optimize a pretreatment and fungal conversion process to enhance the nutritional value of canola meal. Various combinations of physical/chemical pretreatments, fungal cultures, and incubation methods were investigated to metabolize GLS into cell mass, CO2, or other non-toxic components. These treatments also served to hydrolyze canola meal fiber into carbohydrates which were then metabolized by the fungi into single cell protein. Solid-state incubation conditions were initially tested, since filamentous fungi are well adapted to grow at lower moisture levels, and this would potentially reduce contamination issues with bacteria. Flask trials were performed using 50% moisture, hexane extracted (HE) or cold pressed (CP) canola meal, with incubation for 168 h at 30ºC. On HE canola meal Trichoderma reesei (NRRL-3653) achieved the greatest increase in protein content (23%), while having the lowest residual levels of sugar (8% w/w) and GLS (0.4 μM/g). On CP canola meal T. reesei (NRRL-3653), Aureobasidium pullulans (NRRL-58522), and …

The Role Of Dksa In The Stringent Response In The Lyme Disease Spirochete Borrelia Burgdorferi, Britney Cheff

Graduate Student Theses, Dissertations, & Professional Papers

Borrelia burgdorferi, the bacterium that causes Lyme disease, is maintained in nature through an enzootic cycle that includes a tick vector and a vertebrate host. The bacterium is acquired by an Ixodes tick from an infected vertebrate. The bacterium alters its gene expression to adapt to different environments of the tick and vertebrate. Between tick feedings, B. burgdorferi must contend with nutrient stress. The stringent response is a physiological mechanism when bacteria switch from “thriving” to “surviving” mode in response to limited nutrient resources; it is mediated by an increase in the nucleotide alarmone guanosine penta- or tetraphosphate, abbreviated …

Heterotrophic And Autotrophic Contribution To Dinitrogen Fixation In The Gulf Of Aqaba, Eyal Rahav, Barak Herut, Margaret R. Mulholland, Natalia Belkin, Hila Elifantz, Ilana Berman-Frank

OES Faculty Publications

We evaluated the seasonal contribution of heterotrophic and autotrophic diazotrophy to the total dinitrogen (N₂) fixation in the photic zone of a pelagic station in the northern Gulf of Aqaba, Red Sea. N₂ fixation rates were highest during a Trichodesmium bloom in winter (0.7 nmol N l^-1 d^-1), decreased 7-fold 1 wk later throughout the upper 200 m (~0.1 nmol N l^-1) d^-1), and were significantly coupled with both primary and bacterial productivity. N₂ fixation rates were generally higher in the upper 200 m (~0.4 nmol N l^{-1 …}

Iron Deficiency Increases Growth And Nitrogen-Fixation Rates Of Phosphorus-Deficient Marine Cyanobacteria, Nathan S. Garcia, Feixue Fu, Peter N. Sedwick, David A. Hutchins

OES Faculty Publications

Marine dinitrogen (N²)-fixing cyanobacteria have large impacts on global biogeochemistry as they fix carbon dioxide (CO₂) and fertilize oligotrophic ocean waters with new nitrogen. Iron (Fe) and phosphorus (P) are the two most important limiting nutrients for marine biological N₂ fixation, and their availabilities vary between major ocean basins and regions. A long-standing question concerns the ability of two globally dominant N₂-fixing cyanobacteria, unicellular Crocosphaera and filamentous Trichodesmium, to maintain relatively high N₂-fixation rates in these regimes where both Fe and P are typically scarce. We show that under P-deficient …

Elucidation Of A Novel Pathway In Staphylococcus Aureus: The Essential Site-Specific Processing Of Ribosomal Protein L27, Erin A. Wall

Theses and Dissertations

Ribosomal protein L27 is a component of the eubacterial large ribosomal subunit that has been shown to play a critical role in substrate stabilization during protein synthesis. This function is mediated by the L27 N-terminus, which protrudes into the peptidyl transferase center where it interacts with both A-site and P-site tRNAs as well as with 23S rRNA. We observed that L27 in S. aureus and other Firmicutes is encoded with a short N-terminal extension that is not present in most Gram-negative organisms, and is absent from mature ribosomes. The extension contains a conserved cleavage motif; nine N-terminal amino acids are …

Mysteries Of The Trypanosomatid Maxicircles: Characterization Of The Maxicircle Genomes And The Evolution Of Rna Editing In The Order Kinetoplastida, Preethi Ranganathan Iyengar

Theses and Dissertations

The trypanosomatid protists belonging to Order Kinetoplastida are some of the most successful parasites ever known to mankind. Their extreme physiological diversity and adaptability to different environmental conditions and host systems make them some of the most widespread parasites, causing deadly diseases in humans and other vertebrates.

This project focuses on their unique mitochondrion, called the kinetoplast, and more specifically involves the characterization of a part of their mitochondrial DNA (also called kinetoplast DNA or kDNA), the maxicircles, which are functional homologs of eukaryotic mitochondrial DNA in the kinetoplastid protists. We have sequenced and characterized the maxicircle genomes of 20 …

Role Of Extracytoplasmic Rna Polymerase Sigma 70 Factor, Pg0214, In The Survival Of Porphyromonas Gingivalis And In Adaptation To Environmental Stress., David M. Smith

Theses and Dissertations

Porphyromonas gingivalis, a gram-negative anaerobic, pathogenic bacterium is a major etiological agent in the initiation and progression of periodontal disease. Due to the ever-changing environment of the oral cavity, inhabitants like Porphyromonas gingivalis must possess the ability to adapt to changes in environmental conditions like pH, temperature, oxygen tension, and metal concentration. P. gingivalis should therefore have an efficient regulatory system in order to adapt and survive in the oral cavity. This response adaptation occurs at the transcriptional level, which involves alternative sigma factors. Extracytoplasmic function sigma (ECF-s) factors are the largest group of alternative sigma factors that play …

Characterization Of The Interactions Between Staphylococcal Phage 80 Alpha Scaffold And Capsid Proteins, Laura Klenow

Theses and Dissertations

Staphylococcal phage 80α can serve as a helper bacteriophage for a family of mobile genetic elements called Staphylococcus aureus pathogenicity islands (SaPIs). The prototype island, SaPI1, is able to hijack the 80α capsid assembly process and redirect capsid formation to yield smaller, phage-like transducing particles carrying SaPI DNA. Capsid size redirection is accomplished through two SaPI1-encoded gene products, CpmA and an alternate scaffold protein, CpmB. The normal 80α scaffold and the SaPI1 CpmB scaffold share a small block of conserved residues at their C-termini, several of which had been shown to be essential for CpmB function. This led to the …

Characterization Of A Novel Protease In Staphylococcus Aureus, Adam L. Johnson

Theses and Dissertations

A newly discovered cysteine protease, Prp, has been shown to perform an essential, site-specific cleavage of ribosomal protein L27 in Staphylococcus aureus. In Firmicutes and related bacteria, ribosomal protein L27 is encoded with a conserved N-terminal extension that must be removed to expose residues critical for ribosome function. Uncleavable and pre-cleaved variants were unable to complement an L27 deletion in S. aureus, indicating that this N-terminal processing event is essential and likely plays an important regulatory role. The gene encoding the responsible protease (prp) has been shown to be essential, and is found in all organisms …

Self-Cleaning Applications Of Tio2 By Photo-Induced Hydrophilicity And Photocatalysis, Swagata Banerjee, Dionysios Dionysiou, Suresh Pillai

Articles

Self-cleaning materials have gained considerable attention for both their unique properties and practical applications in energy and environmental areas. Recent examples of many TiO2-derived materials have been illustrated to understand the fundamental principles of self-cleaning hydrophilic and hydrophobic surfaces. Various models including those proposed by Wenzel, Cassie-Baxter and Miwa-Hashimoto are discussed to explain the mechanism of self-cleaning. Examples of semiconductor surfaces exhibiting the simultaneous occurrence of superhydrophilic and superhydrophobic domains on the same surface are illustrated, which can have various advanced applications in microfluidics, printing, photovoltaic, biomedical devices, anti-bacterial surfaces and water purification.

Several strategies to improve the efficiency of …

The Effects Of Motility And Chemotaxis On Vibrio Cholerae Colonization In Zebrafish, Paula Dietz

Wayne State University Theses

Vibrio cholerae, the cause of the diarrheal disease cholera, is a gram-negative, curved rod-shaped bacterium, with a single polar flagellum. V. cholerae is naturally found in aquatic environments and is highly motile. When it enters a human host, V. cholerae uses flagellar motility to pass through the stomach and into the small intestine. Once in the small intestine, motility genes are downregulated and virulence gene expression is upregulated. V. cholerae motility and chemotaxis effects have not yet been studied in a zebrafish model, a natural host of this bacterium. We hypothesize that V. cholerae in frame deletions of vital motility …

Francisella Tularensis Catalase Restricts Immune Function By Impairing Trpm2 Channel Activity, Nicole Lynn Flaherty

Legacy Theses & Dissertations (2009 - 2024)

As an innate defense mechanism, macrophages produce reactive species that weaken pathogens and serve as secondary messengers to modify signaling responses involved in immune function. The gram-negative bacterium F. tularensis utilizes its antioxidant armature to limit the host immune response but the mechanism behind this suppression has not been defined. Here we establish that F. tularensis limits Ca2+ entry thereby limiting actin reorganization and IL-6 production in a redox-dependent fashion. Wild-type (LVS) or catalase deficient F. tularensis (∆katG) show distinct profiles in their H2O2 scavenging capacity, 1 pM/sec and 0.015 pM/sec, respectively. Murine alveolar macrophages infected with ∆katG display distinct …

Analysis Of Strategies For Successful Identification, Reporting, And Prevention Of Carbapenem-Resistant Enterobacteriaceae (Cre) In Acute Health Care Facilities In New York State, Christen Leigh Mayer

Legacy Theses & Dissertations (2009 - 2024)

Background

Purification And Characterization Of Bcsc; An Integral Component Of Bacterial Cellulose Export, Emily D. Wilson Ms

Theses and Dissertations (Comprehensive)

Biofilms are a growing concern in the medical field due to their increased resistance to antibiotics. When found in a biofilm, bacteria can have antibiotic resistance 10-1000 times that of their planktonic counterparts. Therefore, it is important to study the formation of biofilms. Cellulose biofilms are formed by Enterobacteriaceae, such as many Escherichia coli and Salmonella spp. strains. Biofilms provide these species with benefits including antimicrobial protection, development of bacterial communities, promotion of DNA exchange, uptake of nutrients, and, in the case of cellulose biofilms, immune system evasion. Cellulose biofilms are controlled by the Bacterial cellulose synthesis (Bcs) complex located …

Whole-Genome Sequencing Of Kaposi’S Sarcoma-Associated Herpesvirus From Zambian Kaposi’S Sarcoma Biopsy Specimens Reveals Unique Viral Diversity, Landon Olp, Adrien Jeanniard, Clemence Marimo, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi’s sarcoma (KS). Both KSHV and KS are endemic in sub-Saharan Africa where approximately 84% of global KS cases occur. Nevertheless, whole-genome sequencing of KSHV has only been completed using isolates from Western countries—where KS is not endemic. The lack of whole-genome KSHV sequence data from the most clinically important geographical region, sub-Saharan Africa, represents an important gap since it remains unclear whether genomic diversity has a role on KSHV pathogenesis. We hypothesized that distinct KSHV genotypes might be present in sub-Saharan Africa compared to Western countries. Using a KSHV-targeted enrichment …

Observed And Expected Incidence Of Cervical Cancer In Lusaka And The Southern And Western Provinces Of Zambia, 2007 - 2012, Mulele Kalima, Kennedy Lishimpi, Jane L. Meza, Shinobu Watanabe-Galloway, Susan C. Msadabwe, Catherine K. Mwaba, Aaron L. Shibemba, Lewis Banda, Charles Wood, Robert M. Chamberlain, Amr S. Soliman

Nebraska Center for Virology: Faculty Publications

Objectives—Cervical cancer is increasing but underestimated in developing countries. We calculated the observed and expected incidence of cervical cancer in Lusaka and Southern and Western provinces of Zambia.

Methods/Materials—Data for 2007-2012 was obtained for the 3 provinces. Data included age, residence, year of diagnosis, marital status, occupation, HIV, stage, radiotherapy and chemotherapy. Expected incidence in Southern and Western provinces was calculated based on observed incidence for Lusaka province, adjusting for HIV.

Results—Crude and age-standardized incidence rates (ASR) in Lusaka were 2-4 times higher than incidence in the other 2 provinces. Lusaka had a rate of 54.1/10⁵ and ASR of …

Crf07_Bc Strain Dominates The Hiv-1 Epidemic In Injection Drug Users In Liangshan Prefecture Of Sichuan, China, Lin Li, Daying Wei, Wan-Ling Hsu, Tianyi Li, Tao Gui, Charles Wood, Yongjian Liu, Hanping Li, Zuoyi Bao, Siyang Liu, Xiaolin Wang, Jingyun Li

Nebraska Center for Virology: Faculty Publications

The Liangshan prefecture in Sichuan province is an area in China severely affected by the HIV epidemic, with intravenous drug use (IDU) as the main risk factor. No reports on HIV subtypes prevalent in IDUs in Liangshan prefecture could be found. In this study, we have characterized the genotypes of HIV-1 in the IDU population in Liangshan prefecture and further determined the phylogenetic relationship of the CRF07_BC strains to HIV-1 sequences from the other regions of China, including Xinjiang and Yunnan provinces, to explore the pattern and possible diffusion pathway of HIV-1 in these regions. HIV-1-seropositive drug-naive IDUs identified in …

Clinical Isolates Of Salmonella Enterica Serovar Agona Producing Ndm-1 Metallo-Beta-Lactamase: First Report From Pakistan, Seema Irfan, Erum Khan, Kauser Jabeen, Pushpa Bhawan, Katie L. Hopkins, Martin Day, Amna Nasir, Daniele Meunier, Neil Woodford

Department of Pathology and Laboratory Medicine

We report two cases of infantile diarrhea due to multidrug-resistant, NDM-1 metallo-beta-lactamase-producing Salmonella enterica serovar Agona from Pakistan. This study alerts toward possible risk of NDM-1 transmission to enteric fever pathogens and encourages microbiologists to consider active screening of carbapenem resistance in nontyphoidal Salmonella isolates.

Hiv Integrase Mechanisms Of Resistance To Raltegravir, Elvitegravir, And Dolutegravir, Kyla Nicole Ross

Wayne State University Theses

ABSTRACT

HIV INTEGRASE MECHANISMS OF RESISTANCE TO RALTEGRAVIR, ELVITEGRAVIR, AND DOLUTEGRAVIR

by

KYLA ROSS

December 2015

Advisor: Dr. Ladislau Kovari

Major: Biochemistry and Molecular Biology

Degree: Master of Science

HIV-1 integrase (HIV-1 IN or IN) is a multimeric enzyme that integrates the HIV-1 genome into the chromosomes of infected CD4+ T-cells. Currently there are three FDA approved HIV-1 IN strand transfer inhibitors (INSTIs) used in clinical practice: raltegravir (RAL), elvitegravir (ELV), and dolutegravir (DTG). The [Q148H], [Q148H, G140S], [Q148R], [Q148R, G140A] and [N155H, E92Q] mutations decrease IN susceptibility to RAL and ELV and may result in therapeutic failure. As an …