Medicine and Health Sciences Commons^™

Nanoscale Interaction Of Endonuclease Ape1 With Dna, Sridhar Vemulapalli, Mohtadin Hashemi, Yingling Chen, Suravi Pramanik, Kishor Bhakat, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Apurinic/apyrimidinic endonuclease 1 (APE1) is involved in DNA repair and transcriptional regulation mechanisms. This multifunctional activity of APE1 should be supported by specific structural properties of APE1 that have not yet been elucidated. Herein, we applied atomic force microscopy (AFM) to characterize the interactions of APE1 with DNA containing two well-separated G-rich segments. Complexes of APE1 with DNA containing G-rich segments were visualized, and analysis of the complexes revealed the affinity of APE1 to G-rich DNA sequences, and their yield was as high as 53%. Furthermore, APE1 is capable of binding two DNA segments leading to the formation of loops …

Assembly Of Synaptic Protein-Dna Complexes: Critical Role Of Non-Specific Interactions, Sridhar Vemulapalli, Mohtadin Hashemi, Anatoly B. Kolomeisky, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

The synaptic protein-DNA complexes, formed by specialized proteins that bridge two or more distant sites on DNA, are critically involved in various genetic processes. However, the molecular mechanism by which the protein searches for these sites and how it brings them together is not well understood. Our previous studies directly visualized search pathways used by SfiI, and we identified two pathways, DNA threading and site-bound transfer pathways, specific to the site-search process for synaptic DNA-protein systems. To investigate the molecular mechanism behind these site-search pathways, we assembled complexes of SfiI with various DNA substrates corresponding to different transient states and …

The Sequence Dependent Nanoscale Structure Of Cenp-A Nucleosomes, Tommy Stormberg, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

CENP-A is a histone variant found in high abundance at the centromere in humans. At the centromere, this histone variant replaces the histone H3 found throughout the bulk chromatin. Additionally, the centromere comprises tandem repeats of α-satellite DNA, which CENP-A nucleosomes assemble upon. However, the effect of the DNA sequence on the nucleosome assembly and centromere formation remains poorly understood. Here, we investigated the structure of nucleosomes assembled with the CENP-A variant using Atomic Force Microscopy. We assembled both CENP-A nucleosomes and H3 nucleosomes on a DNA substrate containing an α-satellite motif and characterized their positioning and wrapping efficiency. We …

Nanorings To Probe Mechanical Stress Of Single-Stranded Dna Mediated By The Dna Duplex, Karen Zagorski, Tommy Stormberg, Mohtadin Hashemi, Anatoly B. Kolomeisky, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

The interplay between the mechanical properties of double-stranded and single-stranded DNA is a phenomenon that contributes to various genetic processes in which both types of DNA structures coexist. Highly stiff DNA duplexes can stretch single-stranded DNA (ssDNA) segments between the duplexes in a topologically constrained domain. To evaluate such an effect, we designed short DNA nanorings in which a DNA duplex with 160 bp is connected by a 30 nt single-stranded DNA segment. The stretching effect of the duplex in such a DNA construct can lead to the elongation of ssDNA, and this effect can be measured directly using atomic …

Crispr-Krispr: A Method To Identify On-Target And Random Insertion Of Donor Dnas And Their Characterization In Knock-In Mice, Masayuki Tanaka, Keiko Yokoyama, Hideki Hayashi, Sanae Isaki, Kanae Kitatani, Ting Wang, Hisako Kawata, Hideyuki Matsuzawa, Channabasavaiah B. Gurumurthy, Hiromi Miura, Masato Ohtsuka

Journal Articles: Pharmacology & Experimental Neuroscience

CRISPR tools can generate knockout and knock-in animal models easily, but the models can contain off-target genomic lesions or random insertions of donor DNAs. Simpler methods to identify off-target lesions and random insertions, using tail or earpiece DNA, are unavailable. We develop CRISPR-KRISPR (CRISPR-Knock-ins and Random Inserts Searching PRotocol), a method to identify both off-target lesions and random insertions. CRISPR-KRISPR uses as little as 3.4 μg of genomic DNA; thus, it can be easily incorporated as an additional step to genotype founder animals for further breeding.

Molecular Characterization Of Cryptosporidium Spp. From Humans In Ethiopia, Ambachew W. Hailu, Abraham Degarege, Haileeyesus Adamu, Damien Costa, Venceslas Villier, Abdelmounaim Mouhajir, Loic Favennec, Romy Razakandrainibe, Beyene Petros

Journal Articles: Epidemiology

Data on the distribution and genotype of Cryptosporidium species is limited in Ethiopia. This study examined the presence and genetic diversity of Cryptosporidium species circulating in Ethiopian human population. Stool samples collected from patients who visited rural (n = 94) and urban (n = 93) health centers in Wurgissa and Hawassa district, respectively, were examined for the presence of Cryptosporidium spp. using microscopy, nested PCR and real-time PCR. To detect infection with PCR, analysis of 18S ribosomal RNA was performed. Subtyping was performed by sequencing a fragment of GP60 gene. The overall prevalence of infection was 46% (n = 86) …

Isolation And Characterization Of A Novel Bacteriophage Wo From Allonemobius Socius Crickets In Missouri, Jonah Kupritz, John Martin, Kerstin Fischer, Kurt C. Curtis, Joseph R. Fauver, Yuefang Huang, Young-Jun Choi, Wandy L. Beatty, Makedonka Mitreva, Peter U. Fischer

Journal Articles: Epidemiology

Wolbachia are endosymbionts of numerous arthropod and some nematode species, are important for their development and if present can cause distinct phenotypes of their hosts. Prophage DNA has been frequently detected in Wolbachia, but particles of Wolbachia bacteriophages (phage WO) have been only occasionally isolated. Here, we report the characterization and isolation of a phage WO of the southern ground cricket, Allonemobius socius, and provided the first whole-genome sequence of phage WO from this arthropod family outside of Asia. We screened A. socius abdomen DNA extracts from a cricket population in eastern Missouri by quantitative PCR for Wolbachia surface protein …

The Mitochondrial Deoxyguanosine Kinase Is Required For Cancer Cell Stemness In Lung Adenocarcinoma, Shengchen Lin, Chongbiao Huang, Jianwei Sun, Oana Bollt, Xiuchao Wang, Eric Martine, Jiaxin Kang, Matthew D. Taylor, Bin Fang, Pankaj K. Singh, John Koomen, Jihui Hao, Shengyu Yang

Journal Articles: Eppley Institute

The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate-limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self-renewal of lung cancer stem-like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self-renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling. …

De Novo Assembly Of The Brugia Malayi Genome Using Long Reads From A Single Minion Flowcell, Joseph R. Fauver, John Martin, Gary J. Weil, Makedonka Mitreva, Peter U. Fischer

Journal Articles: Epidemiology

Filarial nematode infections cause a substantial global disease burden. Genomic studies of filarial worms can improve our understanding of their biology and epidemiology. However, genomic information from field isolates is limited and available reference genomes are often discontinuous. Single molecule sequencing technologies can reduce the cost of genome sequencing and long reads produced from these devices can improve the contiguity and completeness of genome assemblies. In addition, these new technologies can make generation and analysis of large numbers of field isolates feasible. In this study, we assessed the performance of the Oxford Nanopore Technologies MinION for sequencing and assembling the …

Mosquitoes Transmit Unique West Nile Virus Populations During Each Feeding Episode, Nathan D. Grubaugh, Joseph R. Fauver, Claudia Rückert, James Weger-Lucarelli, Selene Garcia-Luna, Reyes A. Murrieta, Alex Gendernalik, Darci R. Smith, Doug E. Brackney, Gregory D. Ebel

Journal Articles: Epidemiology

Arthropod-borne viruses (arboviruses), such as Zika virus, chikungunya virus, and West Nile virus (WNV), pose continuous threats to emerge and cause large epidemics. Often, these events are associated with novel virus variants optimized for local transmission that first arise as minorities within a host. Thus, the conditions that regulate the frequency of intrahost variants are important determinants of emergence. Here, we describe the dynamics of WNV genetic diversity during its transmission cycle. By temporally sampling saliva from individual mosquitoes, we demonstrate that virus populations expectorated by mosquitoes are highly diverse and unique to each feeding episode. After transmission to birds, …

Samhd1 Is A Single-Stranded Nucleic Acid Binding Protein With No Active Site-Associated Nuclease Activity., Kyle J. Seamon, Zhiqiang Sun, Luda S. Shlyakhtenko, Yuri L. Lyubchenko, James T. Stivers

Journal Articles: Pharmaceutical Sciences

The HIV-1 restriction factor SAMHD1 is a tetrameric enzyme activated by guanine nucleotides with dNTP triphosphate hydrolase activity (dNTPase). In addition to this established activity, there have been a series of conflicting reports as to whether the enzyme also possesses single-stranded DNA and/or RNA 3'-5' exonuclease activity. SAMHD1 was purified using three chromatography steps, over which the DNase activity was largely separated from the dNTPase activity, but the RNase activity persisted. Surprisingly, we found that catalytic and nucleotide activator site mutants of SAMHD1 with no dNTPase activity retained the exonuclease activities. Thus, the exonuclease activity cannot be associated with any …

Unbiased Analysis Of Pancreatic Cancer Radiation Resistance Reveals Cholesterol Biosynthesis As A Novel Target For Radiosensitisation., Joshua J. Souchek, Michael J. Baine, Chi Lin, Satyanarayana Rachagani, Suprit Gupta, Sukhwinder Kaur, K Lester, D Zheng, S Chen, Lynette Smith, A Lazenby, Sonny L. Johansson, Maneesh Jain, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Despite its promise as a highly useful therapy for pancreatic cancer (PC), the addition of external beam radiation therapy to PC treatment has shown varying success in clinical trials. Understanding PC radioresistance and discovery of methods to sensitise PC to radiation will increase patient survival and improve quality of life. In this study, we identified PC radioresistance-associated pathways using global, unbiased techniques.

METHODS: Radioresistant cells were generated by sequential irradiation and recovery, and global genome cDNA microarray analysis was performed to identify differentially expressed genes in radiosensitive and radioresistant cells. Ingenuity pathway analysis was performed to discover cellular pathways …

Crystal Structure Of 3wj Core Revealing Divalent Ion-Promoted Thermostability And Assembly Of The Phi29 Hexameric Motor Prna., Hui Zhang, James A. Endrizzi, Yi Shu, Farzin Haque, Claude Sauter, Luda S. Shlyakhtenko, Yuri L. Lyubchenko, Peixuan Guo, Young-In Chi

Journal Articles: Pharmaceutical Sciences

The bacteriophage phi29 DNA packaging motor, one of the strongest biological motors characterized to date, is geared by a packaging RNA (pRNA) ring. When assembled from three RNA fragments, its three-way junction (3WJ) motif is highly thermostable, is resistant to 8 M urea, and remains associated at extremely low concentrations in vitro and in vivo. To elucidate the structural basis for its unusual stability, we solved the crystal structure of this pRNA 3WJ motif at 3.05 Å. The structure revealed two divalent metal ions that coordinate 4 nt of the RNA fragments. Single-molecule fluorescence resonance energy transfer (smFRET) analysis confirmed …

Molecular Epidemiology Of Early And Acute Hiv Type 1 Infections In The United States Navy And Marine Corps, 2005–2010, Richard A. Heipertz, Eric Sanders-Buell, Gustavo Kijak, Shana Howell, Michelle Lazzaro, Linda L. Jagodzinski, John Eggleston, Sheila Peel, Jennifer Malia, Adam Armstrong, Nelson L. Michael, Jerome H. Kim, Robert J. O'Connell, Paul T. Scott, David Brett-Major, Sodsai Tovanabutra

Journal Articles: Epidemiology

The U.S. military represents a unique population within the human immunodeficiency virus 1 (HIV-1) pandemic. The last comprehensive study of HIV-1 in members of the U.S. Navy and Marine Corps (Sea Services) was completed in 2000, before large-scale combat operations were taking place. Here, we present molecular characterization of HIV-1 from 40 Sea Services personnel who were identified during their seroconversion window and initially classified as HIV-1 negative during screening. Protease/reverse transcriptase (pro/rt) and envelope (env) sequences were obtained from each member of the cohort. Phylogenetic analyses were carried out on these regions to determine relatedness within the cohort and …

Low Levels Of Β-Lactam Antibiotics Induce Extracellular Dna Release And Biofilm Formation In Staphylococcus Aureus., Jeffrey B. Kaplan, Era A. Izano, Prerna Gopal, Michael T. Karwacki, Sangho Kim, Jeffrey L. Bose, Kenneth W. Bayles, Alexander R. Horswill

Journal Articles: Pathology and Microbiology

UNLABELLED: Subminimal inhibitory concentrations of antibiotics have been shown to induce bacterial biofilm formation. Few studies have investigated antibiotic-induced biofilm formation in Staphylococcus aureus, an important human pathogen. Our goal was to measure S. aureus biofilm formation in the presence of low levels of β-lactam antibiotics. Fifteen phylogenetically diverse methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains were employed. Methicillin, ampicillin, amoxicillin, and cloxacillin were added to cultures at concentrations ranging from 0× to 1× MIC. Biofilm formation was measured in 96-well microtiter plates using a crystal violet binding assay. Autoaggregation was measured using a visual test tube …

The Role Of Histone H4 Biotinylation In The Structure Of Nucleosomes., Nina A. Filenko, Carol Kolar, John T. West, S. Abbie Smith, Yousef I. Hassan, Gloria E.O. Borgstahl, Janos Zempleni, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

BACKGROUND: Post-translational modifications of histones play important roles in regulating nucleosome structure and gene transcription. It has been shown that biotinylation of histone H4 at lysine-12 in histone H4 (K12Bio-H4) is associated with repression of a number of genes. We hypothesized that biotinylation modifies the physical structure of nucleosomes, and that biotin-induced conformational changes contribute to gene silencing associated with histone biotinylation.

METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis we used atomic force microscopy to directly analyze structures of nucleosomes formed with biotin-modified and non-modified H4. The analysis of the AFM images revealed a 13% increase in the length of DNA …

Dna Synapsis Through Transient Tetramerization Triggers Cleavage By Ecl18ki Restriction Enzyme., Mindaugas Zaremba, Amelia Owsicka, Gintautas Tamulaitis, Giedrius Sasnauskas, Luda S. Shlyakhtenko, Alexander Y. Lushnikov, Yuri L. Lyubchenko, Niels Laurens, Bram Van Den Broek, Gijs J.L. Wuite, Virginijus Siksnys

Journal Articles: Pharmaceutical Sciences

To cut DNA at their target sites, restriction enzymes assemble into different oligomeric structures. The Ecl18kI endonuclease in the crystal is arranged as a tetramer made of two dimers each bound to a DNA copy. However, free in solution Ecl18kI is a dimer. To find out whether the Ecl18kI dimer or tetramer represents the functionally important assembly, we generated mutants aimed at disrupting the putative dimer-dimer interface and analysed the functional properties of Ecl18kI and mutant variants. We show by atomic force microscopy that on two-site DNA, Ecl18kI loops out an intervening DNA fragment and forms a tetramer. Using the …

Modulation Of Edna Release And Degradation Affects Staphylococcus Aureus Biofilm Maturation., Ethan E. Mann, Kelly C. Rice, Blaise R. Boles, Jennifer L. Endres, Dev Ranjit, Lakshmi Chandramohan, Laura H. Tsang, Mark S. Smeltzer, Alexander R. Horswill, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

Recent studies have demonstrated a role for Staphylococcus aureus cidA-mediated cell lysis and genomic DNA release in biofilm adherence. The current study extends these findings by examining both temporal and additional genetic factors involved in the control of genomic DNA release and degradation during biofilm maturation. Cell lysis and DNA release were found to be critical for biofilm attachment during the initial stages of development and the released DNA (eDNA) remained an important matrix component during biofilm maturation. This study also revealed that an lrgAB mutant exhibits increased biofilm adherence and matrix-associated eDNA consistent with its proposed role as an …

Assembly And Development Of The Pseudomonas Aeruginosa Biofilm Matrix., Luyan Ma, Matthew Conover, Haiping Lu, Matthew R. Parsek, Kenneth W. Bayles, Daniel J. Wozniak

Journal Articles: Pathology and Microbiology

Virtually all cells living in multicellular structures such as tissues and organs are encased in an extracellular matrix. One of the most important features of a biofilm is the extracellular polymeric substance that functions as a matrix, holding bacterial cells together. Yet very little is known about how the matrix forms or how matrix components encase bacteria during biofilm development. Pseudomonas aeruginosa forms environmentally and clinically relevant biofilms and is a paradigm organism for the study of biofilms. The extracellular polymeric substance of P. aeruginosa biofilms is an ill-defined mix of polysaccharides, nucleic acids, and proteins. Here, we directly visualize …

Human Muc4 Mucin Induces Ultra-Structural Changes And Tumorigenicity In Pancreatic Cancer Cells., N. Moniaux, P. Chaturvedi, G. C. Varshney, Jane L. Meza, J. F. Rodriguez-Sierra, J-P Aubert, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC4 is a type-1 transmembrane glycoprotein and is overexpressed in many carcinomas. It is a heterodimeric protein of 930 kDa, composed of a mucin-type subunit, MUC4alpha, and a membrane-bound growth factor-like subunit, MUC4beta. MUC4 mRNA contains unique 5' and 3' coding sequences along with a large variable number of tandem repeat (VNTR) domain of 7-19 kb. A direct association of MUC4 overexpression has been established with the degree of invasiveness and poor prognosis of pancreatic cancer. To understand the precise role of MUC4 in pancreatic cancer, we engineered a MUC4 complementary DNA construct, mini-MUC4, whose deduced protein (320 kDa) is …

Site-Specific Labeling Of Supercoiled Dna., Alexander Y. Lushnikov, Vladimir N. Potaman, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Visualization of site-specific labels in long linear or circular DNA allows unambiguous identification of various local DNA structures. Here we describe a novel and efficient approach to site-specific DNA labeling. The restriction enzyme SfiI binds to DNA but leaves it intact in the presence of calcium and therefore may serve as a protein label of 13 bp recognition sites. Since SfiI requires simultaneous interaction with two DNA recognition sites for stable binding, this requirement is satisfied by providing an isolated recognition site in the DNA target and an additional short DNA duplex also containing the recognition site. The SfiI/DNA complexes …

Mitochondrial Dna Mutations, Apoptosis, And The Misfolded Protein Response., Justin L. Mott, Dekui Zhang, Hans Peter Zassenhaus

Journal Articles: Biochemistry & Molecular Biology

Studies of transgenic mice with accelerated accumulation of mtDNA mutations specifically in the heart lead us to propose that apoptotic signaling and cell death is central to the pathogenesis of mtDNA mutations in aging. It is the cellular response to that apoptotic signaling and the organ?s compensatory response to a loss of cells that specify the phenotype of an accumulation of mtDNA mutations. In the heart, cardiomyocytes induce a vigorous anti-apoptotic, pro-survival response to counteract mitochondrial apoptotic signaling. The heart up-regulates contractility of remaining myocytes in order to maintain cardiac output. We hypothesize that mutant mitochondrial proteins originate apoptotic signaling …

Sars Surveillance During Emergency Public Health Response, United States, March-July 2003, Stephanie J. Schrag, John T. Brooks, Chris Van Beneden, Umesh D. Parashar, Patricia M. Griffin, Larry J. Anderson, William J. Bellini, Robert F. Benson, Dean D. Erdman, Alexander Klimov, Thomas G. Ksiazek, Teresa C. T. Peret, Deborah F. Talkington, W. Lanier Thacker, Maria L. Tondella, Jacquelyn S. Sampson, Allen W. Hightower, Dale F. Nordenberg, Brian D. Plikaytis, Ali S. Khan, Nancy E. Rosenstein, Tracee A. Treadwell, Cynthia G. Whitney, Anthony E. Fiore, Tonji M. Durant, Joseph F. Perz, Annemarie Wasley, Daniel Feikin, Joy L. Herndon, William A. Bower, Barbara W. Klibourn, Deborah A. Levy, Victor G. Coronado, Joanna Buffington, Clare A. Dykewicz, Rima F. Khabbaz, Mary E. Chamberland

Journal Articles: Epidemiology

In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of …

Epidemiologic And Environmental Investigation Of A Recreational Water Outbreak Caused By Two Genotypes Of Cryptosporidium Parvum In Ohio In 2000, Els Mathieu, Deborah A. Levy, Fran Veverka, Mary-Kay Parrish, John Sarisky, Nancy Shapiro, Stephanie Johnston, Thomas Handzel, Allen Hightower, Lihua Xiao, Yeuk-Mui Lee, Steve York, Michael Arrowood, Robin Lee, Jeffrey L. Jones

Journal Articles: Epidemiology

In August 2000, the Ohio Department of Health requested assistance to investigate a cryptosporidiosis outbreak with more than 700 clinical case-patients. An epidemiologic and environmental investigation was conducted. Stool specimens, pool water, and sand filter samples were analyzed. A community-based case-control study showed that the main risk factor was swimming in pool A (odds ratio [OR] = 42, 95% confidence interval [CI] = 12.3-144.9). This was supported by results of polymerase chain reaction (PCR) analysis, which showed the presence of both the human and bovine genotypes of Cryptosporidium parvum in case-patients and samples from the filter of pool A. A …

Triplet Repeat Dna Structures And Human Genetic Disease: Dynamic Mutations From Dynamic Dna., Richard R. Sinden, Vladimir N. Potaman, Elena A. Oussatcheva, Christopher E. Pearson, Yuri L. Lyubchenko, Luda S. Shlyakhtenko

Journal Articles: Pharmaceutical Sciences

Fourteen genetic neurodegenerative diseases and three fragile sites have been associated with the expansion of (CTG)n (CAG)n, (CGG)n (CCG)n, or (GAA)n (TTC)n repeat tracts. Different models have been proposed for the expansion of triplet repeats, most of which presume the formation of alternative DNA structures in repeat tracts. One of the most likely structures, slipped strand DNA, may stably and reproducibly form within triplet repeat sequences. The propensity to form slipped strand DNA is proportional to the length and homogeneity of the repeat tract. The remarkable stability of slipped strand DNA may, in part, be due to loop-loop interactions facilitated …

Genetic Variation In Pneumocystis Carinii Isolates From Different Geographic Regions: Implications For Transmission, Charles B. Beard, Jane L. Carter, Scott P. Keely, Laurence Huang, Norman J. Pieniazek, Iaci N. S. Moura, Jacquelin M. Roberts, Allen W. Hightower, Michelle S. Bens, Amanda R. Freeman, Sherline Lee, James R. Stringer, Jeffrey S. Duchin, Carlos Del Rio, David Rimland, Robert P. Baughman, Deborah A. Levy, Vance J. Dietz, Paul Simon, Thomas R. Navin

Journal Articles: Epidemiology

To study transmission patterns of Pneumocystis carinii pneumonia (PCP) in persons with AIDS, we evaluated P. carinii isolates from patients in five U.S. cities for variation at two independent genetic loci, the mitochondrial large subunit rRNA and dihydropteroate synthase. Fourteen unique multilocus genotypes were observed in 191 isolates that were examined at both loci. Mixed infections, accounting for 17.8% of cases, were associated with primary PCP. Genotype frequency distribution patterns varied by patients' place of diagnosis but not by place of birth. Genetic variation at the two loci suggests three probable characteristics of transmission: that most cases of PCP do …