Bacteria Commons^™

Synergistic Cefiderocol-Containing Antibiotic Combinations Active Against Highly Drug-Resistant Acinetobacter Baumannii Patient Isolates With Diverse Resistance Mechanisms, Justin Halim, Andrew P. Keane, Jeannete Bouzo, Tope Aderibigbe, Jessica A. Chicola, Katie T. Nolan, Keertana Jonnalagadda, Jason X. Tran, Valerie J. Carabetta

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Acinetobacter baumannii is a nosocomial pathogen known for rapidly developing resistance to nearly all antibiotics, including last-line agents. Cefiderocol, a novel siderophore cephalosporin, has shown in vitro activity against A. baumannii and is now used clinically, but resistance is emerging. Data on cefiderocol-based antibiotic combinations are limited.

OBJECTIVES: To evaluate the in vitro activity of cefiderocol alone and in combination with other antibiotics against XDR and PDR A. baumannii clinical isolates, and to explore resistance mechanisms underlying cefiderocol synergy.

METHODS: We tested 21 XDR/PDR clinical isolates and one NDM-1-producing strain using broth microdilution and checkerboard assays with cefiderocol and …

Implications Of Type Iv Pilus Retraction For Dna Uptake By Acinetobacter Baumannii, Yafan Yu

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Horizontal gene transfer (HGT) via natural competence allows bacteria to incorporate extracellular DNA (eDNA) into their genomes, facilitating genetic diversity and adaptation. In Acinetobacter species, natural competence depends on DNA binding and uptake mediated by type IV pili (T4P). T4P are dynamic extracellular filaments composed primarily of the major pilin subunit PilA, along with a few minor subunits. T4P drive a range of cellular functions including twitching motility, biofilm formation, and DNA uptake, with some functions dependent on pilus retraction and others not. However, how Acinetobacter T4P bind DNA and how T4P/eDNA interactions impact biofilm formation remain unclear. Here, I …

Evaluation Of The Efficacy Of Novel Drugs And Combinations Against Extensively- And Pan-Drug Resistant Acinetobacter Baumannii Isolates, Keertana Jonnalagadda, Rachel Carr, Valerie Carabetta

Rowan-Virtua Research Day

Acinetobacter baumannii, a Gram-negative, nosocomial, opportunistic pathogen is commonly infectious in immunocompromised patients. More specifically patients develop healthcare-associated infections (HAI) spanning beyond sepsis, pneumonia, meningitis, and urinary tract infections. Due to its rapid ability to acquire antibiotic resistance, it has raised the necessity to discern a novel therapeutic treatment that can be effectively used against the multidrug resistant (MDR) A. baumannii. Cooper University Hospital (CUH) faced an increased case load of patients that were infected with MDR A. baumannii. The patient isolates obtained from CUH were highly resistant to the 22 standard-of-care antibiotics. With the recent introduction …

Cyclic-Di-Gmp-Binding Proteins Regulate Acinetobacter Baumannii Motility, Gabriel Smith

Undergraduate Honors Theses

Acinetobacter baumannii is a prevalent nosocomial pathogen where, like many other infectious bacteria, A. baumannii is increasingly considered a multi-drug resistant pathogen. This research study was designed to find a way to affect the persistence of A. baumannii such that it can be applied to a hospital setting to prevent further nosocomial infections. One regulatory mechanism potentially used by A. baumannii to persist on hospital surfaces is through the use of the bacterial second messenger cyclic-di-GMP (c-di-GMP). This nucleotide signal is regulated in response to environmental conditions, and then activates c-di-GMP-binding proteins that induce phenotypic changes. One c-di-GMP-regulated phenotype is …

Second Messenger Cyclic-Di-Gmp Regulation In Acinetobacter Baumannii, Justin Deal

Undergraduate Honors Theses

Over time, “superbugs,” or bacteria that have become resistant to antibiotics, have become a great concern in modern medicine. Viable alternates are currently being looked into as effective and safe ways to prevent or treat infections caused by these superbugs. One such method is through the utilization of the second messenger molecule cyclic-di-GMP (c-di-GMP) that has been shown to regulate phenotypes within other bacteria that may control surface colonization in Acinetobacter baumannii. Through a series of experiments, the active enzymes that create c-di-GMP - diguanylate cyclases - and break down c-di- GMP - phosphodiesterases - have been inactivated in …