Cell and Developmental Biology Commons^™

The Role Of Seed Mix Characteristics And Soil Amendments During Post-Agricultural Prairie Restoration, Valerie N. Thurston, Michaela J. Woods, Madelaine Gregory, Mary C. Lloyd, Ryan W. Mcewan

Biology Faculty Publications

Introduction: Prairie restoration on degraded lands may be influenced by seed mix characteristics, including species richness and legume establishment. Soil amendments may facilitate restoration; however, the practical usefulness of techniques such as applications of whole soil and leaf mulch remains relatively unclear.

Objectives: We assessed whether increasing species richness and legume content in seed mixes enhances prairie restoration success and examined how soil amendments interact with seed mix composition to influence cover, species richness, diversity, and legume establishment.

Methods: We conducted a field experiment on a 12-ha post-agricultural site in Ohio, U.S.A. Twenty 50 × 50 m plots received one …

Protocol For Vibratome Sectioning, Immunofluorescence, And S-Phase Labeling Of Inner Ear Organoids, Jiayi Wu, Stefan Heller, Maggie S. Matern

Biology Faculty Publications

Inner ear organoids represent a potentially inexhaustible source of otic tissues, including sensory hair cells and supporting cells, for in vitro manipulation. Here, we present a protocol for labeling S-phase entry of cells in inner ear organoids using 5-ethynyl-2′-deoxyuridine (EdU), followed by fixation and vibratome sectioning. Nuclear EdU is then detected alongside protein markers of interest via immunofluorescence. This workflow enables the visualization of cell and tissue morphologies within developing organoids and assessment of how different manipulations affect cell proliferation.

In Silico Prediction Of Cytotoxic T-Cell Epitopes From Helicobacter Pylori Virulence Factors Using An Immunoinformatics Approach, Demy Valerie Chacon, Kiana Alika Co, Daphne Noreen Enriquez, Aubrey Love Labarda, Reanne Eden Manongsong, Edward Kevin B. Bragais

Biology Faculty Publications

Background: Helicobacter pylori infects approximately half of the global population, leading to gastric and duodenal ulcers. Despite the availability of antibiotics, challenges such as patient reluctance, high treatment costs, and antibiotic resistance limit their effectiveness, making vaccination a promising alternative. This study used immunoinformatics to identify candidate epitopes for a multiepitope vaccine construct against H. pylori.

Material and methods: The protein variability server was utilized for conservation analysis. The epitopes were screened for antigenicity, allergenicity, toxicity, cross-reactivity, and population coverage. Selected epitopes were docked with their corresponding human leukocyte antigen (HLA) alleles, and thermodynamic quantities were determined. Five virulence …

Neuronal And Glial Cell Alterations Involved In The Retinal Degeneration Of The Familial Dysautonomia Optic Neuropathy, Anastasia Schultz, Henar Albertos-Arranz, Xavier Sánchez Sáez, Jamie Morgan, Diane Darland, Alejandra Gonzalez-Duarte, Horacio Kaufmann, Carlos E. Mendoza-Santiesteban, Nicolás Cuenca, Frances Lefcort

Biology Faculty Publications

Familial dysautonomia (FD) is a rare genetic neurodevelopmental and neurodegenerative disorder. In addition to the autonomic and peripheral sensory neuropathies that challenge patient survival, one of the most debilitating symptoms affecting patients' quality of life is progressive blindness resulting from the steady loss of retinal ganglion cells (RGCs).Within the FD community, there is a concerted effort to develop treatments to prevent the loss of RGCs. However, the mechanisms underlying the death of RGCs are not well understood. To study the mechanisms underlying RGC death, Pax6-cre;Elp1loxp/loxp male and female mice and postmortem retinal tissue from an FD patient were used to …

The Plant Disease Triangle Facing Climate Change: A Molecular Perspective, Charles Roussin-Léveillée, Christina A. M. Rossi, Christian Castroverde, Peter Moffett

Biology Faculty Publications

No abstract provided.

Consequences Of Spatial Structure In Soil–Geomorphic Data On The Results Of Machine Learning Models, Daehyun Kim, Insang Song, Lorrayne Miralha, Daniel R. Hirmas, Ryan W. Mcewan, Tom G. Mueller, Pavel Samonil

Biology Faculty Publications

In this paper, we examined the degree to which inherent spatial structure in soil properties influences the outcomes of machine learning (ML) approaches to predicting soil spatial variability. We compared the performances of four ML algorithms (support vector machine, artificial neural network, random forest, and random forest for spatial data) against two non-ML algorithms (ordinary least squares regression and spatial filtering regression). None of the ML algorithms produced residuals that had lower mean values or were less autocorrelated over space compared with the non-ML approaches. We recommend the use of random forest when a soil variable of interest is weakly …

Mitochondrial Gtp Metabolism Controls Reproductive Aging In C. Elegans, Yi-Tang Lee, Marzia Savini, Tao Chen, Yang, Jin, Qian Zhao, Lang Ding, Shihong Max Gao, Jessica N. Sowa, Jue D. Wang, Meng C. Wang

Biology Faculty Publications

Healthy mitochondria are critical for reproduction. During aging, both reproductive fitness and mitochondrial homeostasis decline. Mitochondrial metabolism and dynamics are key factors in supporting mitochondrial homeostasis. However, how they are coupled to control reproductive health remains unclear. We report that mitochondrial GTP (mtGTP) metabolism acts through mitochondrial dynamics factors to regulate reproductive aging. We discovered that germline-only inactivation of GTP-but not ATP-specific succinyl-CoA synthetase (SCS) promotes reproductive longevity in Caenorhabditis elegans. We further identified an age-associated increase in mitochondrial clustering surrounding oocyte nuclei, which is attenuated by GTP-specific SCS inactivation. Germline-only induction of mitochondrial fission factors sufficiently promotes mitochondrial dispersion …

Transcriptional Pausing Factor M1bp Regulates Cellular Homeostasis By Suppressing Autophagy And Apoptosis In Drosophila Eye, Anuradha Venkatakrishnan Chimata, Hannah Darnell, Akanksha Raj, Madhuri Kango-Singh

Biology Faculty Publications

During organogenesis cellular homeostasis plays a crucial role in patterning and growth. The role of promoter proximal pausing of RNA polymerase II, which regulates transcription of several developmental genes by GAGA factor or Motif 1 Binding Protein (M1BP), has not been fully understood in cellular homeostasis. Earlier, we reported that M1BP, a functional homolog of ZKSCAN3, regulates wingless (wg) and caspase-dependent cell death (apoptosis) in the Drosophila eye. Further, blocking apoptosis does not fully rescue the M1BP^RNAi phenotype of reduced eye. Therefore, we looked for other possible mechanism(s). In a forward genetic screen, members of the Jun-amino-terminal-(NH2)-Kinase (JNK) pathway …

N-Acetyltransferase 9 Ameliorates Aβ42-Mediated Neurodegeneration In The Drosophila Eye, Prajakta Deshpande, Anuradha Venkatakrishnan Chimata, Emily E. Snider, Aditi Singh, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, manifests as accumulation of amyloid-beta-42 (Aβ42) plaques and intracellular accumulation of neurofibrillary tangles (NFTs) that results in microtubule destabilization. Targeted expression of human Aβ42 (GMR > Aβ42) in developing Drosophila eye retinal neurons results in Aβ42 plaque(s) and mimics AD-like extensive neurodegeneration. However, there remains a gap in our understanding of the underlying mechanism(s) for Aβ42-mediated neurodegeneration. To address this gap in information, we conducted a forward genetic screen, and identified N-acetyltransferase 9 (Mnat9) as a genetic modifier of GMR > Aβ42 neurodegenerative phenotype. Mnat9 is known to stabilize microtubules by inhibiting c-Jun-N- …

Structural Diversity And Stress Regulation Of The Plant Immunity-Associated Calmodulin-Binding Protein 60 (Cbp60) Family Of Transcription Factors In Solanum Lycopersicum (Tomato), Vanessa Shivnauth, Sonya Pretheepkumar, Eric J. R. Marchetta, Christina A. M. Rossi, Keaun Amani, Christian Castroverde

Biology Faculty Publications

Cellular signaling generates calcium (Ca2+) ions, which are ubiquitous secondary messengers decoded by calcium-dependent protein kinases, calcineurins, calreticulin, calmodulins (CAMs), and CAM-binding proteins. Previous studies in the model plant Arabidopsis thaliana have shown the critical roles of the CAM-BINDING PROTEIN 60 (CBP60) protein family in plant growth, stress responses, and immunity. Certain CBP60 factors can regulate plant immune responses, like pattern-triggered immunity, effector-triggered immunity, and synthesis of major plant immune-activating metabolites salicylic acid (SA) and N-hydroxypipecolic acid (NHP). Although homologous CBP60 sequences have been identified in the plant kingdom, their function and regulation in most species remain unclear. In …

Pyrus Calleryana Extracts Reduce Germination Of Native Grassland Species, Suggesting The Potential For Allelopathic Effects During Ecological Invasion, Michaela J. Woods, Jonathan T. Bauer, Dena Schaeffer, Ryan W. Mcewan

Biology Faculty Publications

Invasive plant species’ success may be a result of allelopathy, or the release of secondary metabolites that are harmful for surrounding plant species. Allelopathy can be mediated through the abiotic environment by chemical sorption or transformation, so the substrate on which interactions occur can lead to differential outcomes in allelopathic potential. One aggressive invader, Pyrus calleryana, has become dominant in many ecosystems throughout Eastern US, and has reduced the abundance of native species where it invades. Thus, our goal was to identify if P. calleryana had allelopathic potential by testing the impact of leaf and flower leachate on gemination …

Surveillance And Stewardship: Where Infection Prevention And Antimicrobial Stewardship Intersect, Fred C. Tenover, Debra A. Goff

Biology Faculty Publications

Colonization with multidrug-resistant organisms (MDROs) is a risk factor for subsequent infection. Surveillance for MDROs, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Enterobacterales, and carbapenemase-producing organisms, is commonly conducted in hospitals to prevent spread of MDROs, in part to reduce the potential for additional infections. Although colonization is a risk factor for infection, data on colonization with various MDROs are often not considered when selecting anti-infective therapy. There are conflicting data on the strength of the positive and negative predictive values of the colonization test results to guide therapeutic strategies. Defining therapeutic strategies for patients with complicated or …

Myo19 Tethers Mitochondria To Endoplasmic Reticulum-Associated Actin To Promote Mitochondrial Fission, Stephen M. Coscia, Cameron P. Thompson, Qing Tang, Elana E. Baltrusaitis, Joseph A. Rhodenhiser, Omar A. Quintero, E. Michael Ostap, Melike Lakadamyali, Erika L. Holzbaur

Biology Faculty Publications

Mitochondrial homeostasis requires a dynamic balance of fission and fusion. The actin cytoskeleton promotes fission, and we found that the mitochondrially localized myosin, myosin 19 (Myo19), is integral to this process. Myo19 knockdown induced mitochondrial elongation, whereas Myo19 overexpression induced fragmentation. This mitochondrial fragmentation was blocked by a Myo19 mutation predicted to inhibit ATPase activity and strong actin binding but not by mutations predicted to affect the working stroke of the motor that preserve ATPase activity. Super-resolution imaging indicated a dispersed localization of Myo19 on mitochondria, which we found to be dependent on metaxins. These observations suggest that Myo19 acts …

A Trial Of Fire And Ice: Assessment Of Control Techniques For Pyrus Calleryana Invasion Of Grasslands In Southwestern Ohio, Usa, Margaret E. Maloney, Eric B. Borth, Grace Dietsch, Mary C. Lloyd, Ryan W. Mcewan

Biology Faculty Publications

Pyrus calleryana (Callery pear) is an invasive plant that threatens ecosystems in the eastern United States. We investigated the efficacy of various control techniques on P. calleryana invasion in grasslands. Treatments were applied to (a) P. calleryana stems that had experienced mowing annually for several years and were sprouting (n = 100 stems; “trees-sprouting”) and (b) stems that had established ca. 10 years earlier, had never been cut, and were single-stemmed trees (n = 40 stems; “trees-intact”). In both experiments, existing stems were cut and randomly assigned one of the following treatments: cut only (control), burning, freezing, or herbicide, and …

Directed Carbapenemase Testing Is No Longer Just For Enterobacterales: Cost, Labor, And Workflow Assessment Of Expanding Carbapenemase Testing To Carbapenem-Resistant P. Aeruginosa, Fred C. Tenover, Christian M. Gill, Poonam Rajkotia, Amity L. Roberts, David P. Nicolau

Biology Faculty Publications

Molecular carbapenem-resistance testing, such as for the presence of carbapenemases genes, is commonly implemented for the detection of carbapenemase-producing Enterobacterales. Carbapenemase-producing P. aeruginosa is also associated with significant morbidity and mortality, although; prevalence may be underappreciated in the United States due to a lack of carbapenemase testing. The present study sought to compare hands-on time, cost and workflow implementation of carbapenemase gene testing in Enterobacterales and P. aeruginosa isolates versus sending out isolates to a public health laboratory (PHL) for testing to assess if in-house can provide actionable results. The time to carbapenemase gene results were compared. Differences in cost …

Molecular Regulation Of The Salicylic Acid Hormone Pathway In Plants Under Changing Environmental Conditions, Christina A. M. Rossi, Eric J. R. Marchetta, Jong Hum Kim, Christian Castroverde

Biology Faculty Publications

Salicylic acid (SA) is a central plant hormone mediating immunity, growth, and development. Recently, studies have highlighted the sensitivity of the SA pathway to changing climatic factors and the plant microbiome. Here we summarize organizing principles and themes in the regulation of SA biosynthesis, signaling, and metabolism by changing abiotic/biotic environments, focusing on molecular nodes governing SA pathway vulnerability or resilience. We especially highlight advances in the thermosensitive mechanisms underpinning SA-mediated immunity, including differential regulation of key transcription factors (e.g., CAMTAs, CBP60g, SARD1, bHLH059), selective protein–protein interactions of the SA receptor NPR1, and dynamic phase separation of the recently identified …

A Pooling Strategy For Detecting Carbapenem Resistance Genes By The Xpert Carba-R Test In Rectal Swab Specimens, Fred C. Tenover, Peng Zhang, Qi Wang, Chaoe Zhou, Feifei Zhang, Xinghui Gao, Yi-Wei Tang, Hui Wang

Biology Faculty Publications

Rapid and accurate detection of carriers of carbapenemase-producing organisms (CPO) in hospitalized patients is critical for infection control and prevention. This study aimed to evaluate a pooling strategy for the detection of carbapenem resistance genes (CRG) in multiple specimens using the Xpert Carba-R test. Two rectal swabs each were collected from 415 unique patients. One swab was tested by Carba-R on the five specimen-pooled strategy. The other swab was tested individually by culture followed by DNA sequence analysis for CRG as the reference. At the first 5:1 pooling testing, 22 of 83 pools were positive, which yielded 34 positives from …

Leaf Phenology And Freeze Tolerance Of The Invasive Tree Pyrus Calleryana (Roseaceae) And Potential Native Competitors, Margaret E. Maloney, Abby Hay, Eric B. Borth, Ryan W. Mcewan

Biology Faculty Publications

Pyrus calleryana is one of the most problematic invasive species in the eastern United States. The mechanisms that enable Py. calleryana to establish and outcompete native plants are not fully understood but likely include a profile of advantageous traits. Extended leaf phenology is a characteristic noted in many woody invasive plants. Leaf phenology of Py. calleryana and two native woody species, Populus deltoides and Platanus occidentalis, was observed in natural areas near Dayton, OH from December 2019 to November 2020. A frost event in May also gave us the serendipitous opportunity to assess frost tolerance of these species. We …

Mechanisms Of Carbapenemase-Mediated Resistance Among High-Risk Pseudomonas Aeruginosa Lineages In Peru, Isabella A. Tickler, Juan Carlos Gomez De La Torre, Luis Alvarado, Anne E. Obradovich, Fred C. Tenover

Biology Faculty Publications

Objectives: Pseudomonas aeruginosa is one of the leading causes of healthcare-associated infections globally. High-risk carbapenemase-encoding P. aeruginosa clones are disseminating in many regions. The aim of this study was to learn more about the lineages and mechanisms of resistance of P. aeruginosa circulating in Peru.

Methods: A total of 141 carbapenemase-producing isolates recovered from hospitalized and ambulatory patients in Lima were sequenced and analyzed to infer their lineages through whole-genome sequence typing (wgST) and to identify their antimicrobial resistance genes.

Results: wgST identified nine sequence types (STs); ST111 and ST357 were the most frequently encountered (44.0% and 38.3%, respectively), followed …

Increasing The Resilience Of Plant Immunity To A Warming Climate, Jong Hum Kim, Christian Castroverde, Shuai Huang, Chao Li, Richard Hilleary, Adam Seroka, Reza Sohrabi, Diana Medina-Yerena, Bethany Huot, Jie Wang, Sharon Marr, Mary Wildermuth, Tao Chen, John Macmicking, Sheng Yang He

Biology Faculty Publications

Extreme weather conditions associated with climate change affect many aspects of plant and animal life, including the response to infectious diseases. Production of salicylic acid (SA), a central plant defence hormone, is particularly vulnerable to suppression by short periods of hot weather above the normal plant growth temperature range via an unknown mechanism. Here we show that suppression of SA production in Arabidopsis thaliana at 28 °C is independent of PHYTOCHROME B (phyB) and EARLY FLOWERING 3 (ELF3), which regulate thermo-responsive plant growth and development. Instead, we found that formation of GUANYLATE BINDING PROTEIN-LIKE 3 (GBPL3) defence-activated biomolecular condensates (GDACs) …

Characterization Of SccMec Instability In Methicillin-Resistant Staphylococcus Aureus Affecting Adjacent Chromosomal Regions, Including The Gene For Staphylococcal Protein A (Spa), Isabella A. Tickler, Fred C. Tenover, C. R. Scharn, R. V. Goering

Biology Faculty Publications

Staphylococcal cassette chromosome mec (SCCmec) represents a sequence of clear clinical and diagnostic importance in staphylococci. At a minimum the chromosomal cassette contains the mecA gene encoding PBP2a but frequently also includes additional antibiotic resistance genes (e.g., ermA and aadC; macrolide and aminoglycoside resistance, respectively). Certain regions within SCCmec elements are hot spots for sequence instability due to cassette-specific recombinases and a variety of internal mobile elements. SCCmec changes may affect not only cassette stability but the integrity of adjacent chromosomal sequences (e.g., the staphylococcal protein A gene; spa). We investigated SCCmec stability …

Salicylic Acid And N-Hydroxypipecolic Acid At The Fulcrum Of The Plant Immunity-Growth Equilibrium, Alyssa Shields, Vanessa Shivnauth, Christian Danve M. Castroverde

Biology Faculty Publications

Salicylic acid (SA) and N-hydroxypipecolic acid (NHP) are two central plant immune signals involved in both resistance at local sites of pathogen infection (basal resistance) and at distal uninfected sites after primary infection (systemic acquired resistance). Major discoveries and advances have led to deeper understanding of their biosynthesis and signaling during plant defense responses. In addition to their well-defined roles in immunity, recent research is emerging on their direct mechanistic impacts on plant growth and development. In this review, we will first provide an overview of how SA and NHP regulate local and systemic immune responses in plants. We …

Carbapenemase-Producing Pseudomonas Aeruginosa – An Emerging Challenge, Fred C. Tenover, David P. Nicolau, Christian M. Gill

Biology Faculty Publications

Carbapenem-resistant Pseudomonas aeruginosa (CR-PA) is a major healthcare-associated pathogen worldwide. In the United States, 10–30% of P. aeruginosa isolates are carbapenem-resistant, while globally the percentage varies considerably. A subset of carbapenem-resistant P. aeruginosa isolates harbour carbapenemases, although due in part to limited screening for these enzymes in clinical laboratories, the actual percentage is unknown. Carbapenemase-mediated carbapenem resistance in P. aeruginosa is a significant concern as it greatly limits the choice of anti-infective strategies, although detecting carbapenemase-producing P. aeruginosa in the clinical laboratory can be challenging. Such organisms also have been associated with nosocomial spread requiring infection prevention interventions. The carbapenemases …

Detection Of Methicillin-Resistant Staphylococcus Aureus Infections Using Molecular Methods, Fred C. Tenover, Isabella A. Tickler

Biology Faculty Publications

The application of molecular detection methods for bacterial pathogens has dramatically improved the outcomes of septic patients, including those with methicillin-resistant Staphylococcus aureus (MRSA) infections. Molecular methods can be applied to a variety of clinical specimens including nasal swabs, growth in blood culture bottles, and wounds. While data show that the overall accuracy of molecular tests for MRSA is high, results can be confounded by the presence of multiple staphylococcal species in a specimen, insertions and deletions of DNA in and around the Staphylococcal Cassette Chromosome mec (SCCmec) element, and point mutations in mecA. Herein, we explore the complexities of …

Clinical Performance Of The Xpert® Ct/Ng Test For Detection Of Chlamydia Trachomatis And Neisseria Gonorrhoeae: A Multicenter Evaluation In Chinese Urban Hospitals, Fred C. Tenover, Yan Han, Mei-Qin Shi, Qing-Ping Jiang, Wen-Jing Le, Xiao-Lin Qin, Han-Zhen Xiong, He-Ping Zheng, Yi-Wei Tang, Yue-Ping Yin

Biology Faculty Publications

Background: We aimed to evaluate the clinical performance of the GeneXpert® (Xpert) CT/NG assay for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using urine and cervical swabs collected from patients in China.

Methods: This study was conducted from September 2016 to September 2018 in three Chinese urban hospitals. The results from the Xpert CT/NG test were compared to those from the Roche cobas® 4800 CT/NG test. Discordant results were confirmed by DNA sequence analysis.

Results: In this study, 619 first void urine (FVU) specimens and 1,042 cervical swab specimens were included in the final dataset. There were …

Developing Inside A Layer Of Germs—A Potential Role For Multiciliated Surface Cells In Vertebrate Embryos, Ryan R. Kerney

Biology Faculty Publications

This paper reviews current research on the microbial life that surrounds vertebrate embryos. Several clades are believed to develop inside sterile—or near-sterile—embryonic microhabitats, while others thrive within a veritable zoo of microbial life. The occurrence of embryo-associated microbes in some groups, but not others, is an under-appreciated transition (possibly transitions) in vertebrate evolution. A lack of comparable studies makes it currently impossible to correlate embryo-associated microbiomes with other aspects of vertebrate evolution. However, there are embryonic features that should instruct a more targeted survey. This paper concludes with a hypothesis for the role of multiciliated surface cells in amphibian and …

Development Of Alveolar-Capillary-Exchange (Ace) Chip And Its Application For Assessment Of Pm2.5-Induced Toxicity, Mingyang Gang, Song Tang, Haiyun Chang, Yuanyuan Chen, Fengge Chen, Ying Mu, Dong Zhao, Weiwei Fan, Huifang Tian, Diane Darland, Ying Zhang

Biology Faculty Publications

Although standard two-dimensional (2D) cell culture is an effective tool for cell studies, monolayer cultivation can yield imperfect or misleading information about numerous biological functions. In this study, we developed an alveolar-capillary exchange (ACE) chip aiming to simulate the cellular microenvironment at the alveolar-capillary interface. The ACE chip was designed with two chambers for culturing alveolar epithelial cells and vascular endothelial cells separately, which are separated by a microporous polycarbonate film that allows for the exchange of soluble biomolecules. Using this model, we further tested the toxic effects of fine particulate matter (PM2.5), a form of airborne pollutant known to …

Salicylic Acid: A Key Regulator Of Redox Signalling 1 And Plant Immunity, Mohd Saleem, Qazi Fariddudin, Christian Castroverde

Biology Faculty Publications

In plants, the reactive oxygen species (ROS) formed during normal conditions are essential in regulating several processes, like stomatal physiology, pathogen immunity and developmental signaling. However, biotic and abiotic stresses can cause ROS over-accumulation leading to oxidative stress. Therefore, a suitable equilibrium is vital for redox homeostasis in plants, and there have been major advances in this research arena. Salicylic acid (SA) is known as a chief regulator of ROS; however, the underlying mechanisms remain largely unexplored. SA plays an important role in establishing the hypersensitive response (HR) and systemic acquired resistance (SAR). This is underpinned by a robust and …

Using Molecular Diagnostics To Develop Therapeutic Strategies For Carbapenem-Resistant Gram-Negative Infections, Fred C. Tenover

Biology Faculty Publications

Infections caused by multidrug-resistant Gram-negative organisms have become a global threat. Such infections can be very difficult to treat, especially when they are caused by carbapenemase-producing organisms (CPO). Since infections caused by CPO tend to have worse outcomes than non-CPO infections, it is important to identify the type of carbapenemase present in the isolate or at least the Ambler Class (i.e., A, B, or D), to optimize therapy. Many of the newer beta-lactam/beta-lactamase inhibitor combinations are not active against organisms carrying Class B metallo-enzymes, so differentiating organisms with Class A or D carbapenemases from those with Class B enzymes rapidly …

Phenotypic/Genotypic Profile Of Oxa-10-Like-Harboring, Carbapenem-Resistant Pseudomonas Aeruginosa: Using Validated Pharmacokinetic/Pharmacodynamic In Vivo Models To Further Evaluate Enzyme Functionality And Clinical Implications, Fred C. Tenover, Christian M. Gill, Adrian Brink, Chun Yat Chu, Jennifer Coetzee, George Dimopoulos, Clinton Moodley, Christoffel Johannes Opperman, Spyros Pournaras, Isabella A. Tickler, Hafsah Deepa Tootla, Sophia Vourli, David P. Nicolau

Biology Faculty Publications

In vitro MICs and in vivo pharmacodynamics of ceftazidime and cefepime human-simulated regimens (HSR) against modified carbapenem inactivation method (mCIM)-positive Pseudomonas aeruginosa isolates harboring different OXA-10-like subtypes were described. The murine thigh model assessed ceftazidime (2 g every 8 h [q8h] HSR) and cefepime (2 g and 1 g q8h HSR). Phenotypes were similar despite possessing OXA-10-like subtypes with differing spectra. Ceftazidime produced ≥1-log10 killing in all isolates. Cefepime activity was dose dependent and MIC driven. This approach may be useful in assessing the implications of β-lactamase variants.