A5073031989- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- Vibrio bacteria research studies
- Lipid Membrane Structure and Behavior
- Immune Response and Inflammation
- Escherichia coli research studies
- Salmonella and Campylobacter epidemiology
- Bacteriophages and microbial interactions
- Metabolomics and Mass Spectrometry Studies
- Helicobacter pylori-related gastroenterology studies
- Bacterial biofilms and quorum sensing
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Mass Spectrometry Techniques and Applications
- Antimicrobial Peptides and Activities
- Enzyme Structure and Function
- Veterinary medicine and infectious diseases
- Galectins and Cancer Biology
- Viral gastroenteritis research and epidemiology
- Probiotics and Fermented Foods
- Gut microbiota and health
- Drug Transport and Resistance Mechanisms
- Clostridium difficile and Clostridium perfringens research
- Microbial infections and disease research
- Advanced Proteomics Techniques and Applications
University of Georgia
2015-2024
Georgia College & State University
2015-2021
Franklin College
2019-2021
Florida State University
2020
The University of Texas at Austin
2008-2016
Texas Center for Infectious Disease
2014-2015
Institut de Biologie Moléculaire et Cellulaire
2013
Laboratory of Molecular Genetics
2010-2012
Augusta University
2007-2008
In-Q-Tel
2007
Gut microbes resist inflammation It is vital to human well-being that our gut microbiota can be distinguished from harmful, but often very similar, organisms. Cullen et al. begin analyze how one dominant symbiont, Bacteroidetes thetaiotaomicron , does this. Our guts release potent antimicrobial peptides when we become infected with pathogenic bacteria such as salmonella, these symbionts make an outer lipopolysaccharide coat differs those of pathogens by only phosphate molecule. Enzymatic...
ABSTRACT The emergence of multidrug resistance among Acinetobacter baumannii is leading to an increasing dependence on the use polymyxins as last-hope antibiotics. Here, we utilized genetic and biochemical methods define involvement pmrCAB operon in polymyxin this organism. Sequence analysis 16 B-resistant strains, including 6 spontaneous mutants derived from strain ATCC 17978 10 clinical isolates diverse sources, revealed that they had independent mutations pmrB gene, encoding a sensor...
Despite its highly inflammatory nature, LPS is a molecule with remarkable therapeutic potential. Lipid A glycolipid that serves as the hydrophobic anchor of and constitutes potent ligand Toll-like receptor (TLR)4/myeloid differentiation factor 2 innate immune system. less toxic mixture monophosphorylated lipid species (MPL) recently became first new Food Drug Administration-approved adjuvant in over 70 y. Whereas wild-type Escherichia coli provokes strong MyD88 (myeloid primary response gene...
Rates of infection with hospital-acquired Acinetobacter baumannii have exploded over the past decade due to our inability limit persistence and effectively treat disease. A. quickly acquires antibiotic resistance, its genome encodes mechanisms tolerate biocides desiccation, which enhance in hospital settings. With depleted options, new methods infections are desperately needed. A comprehensive understanding detailing cellular factors that contribute resiliency at genetic mechanistic levels...
Attachment of the cationic sugar 4-amino-4-deoxy-l-arabinose (l-Ara4N) to lipid A is required for maintenance polymyxin resistance inEscherichia coli and Salmonella typhimurium. The enzymes that synthesize l-Ara4N transfer it have not been identified. We now report an inner membrane enzyme, expressed in polymyxin-resistant mutants, adds one or twol-Ara4N moieties its immediate precursors. No soluble factors are required. gene located near minute 51 on theS. typhimurium E. chromosomes...
Lipopolysaccharide or LPS is localized to the outer leaflet of membrane and serves as major surface component bacterial cell envelope. This remarkable glycolipid essential for virtually all Gram-negative organisms represents one conserved microbial structures responsible activation innate immune system. For these reasons, structure, function, biosynthesis has been an area intense research. The a number bacteria composed three distinct regions — lipid A, short core oligosaccharide, O-antigen...
Pathogenic bacteria modify the structure of lipid A portion their lipopolysaccharide in response to environmental changes. Some modifications are important for virulence and resistance cationic antimicrobial peptides. The two-component system PhoP/PhoQ plays a central role regulating modification. We now report discovery PhoP/PhoQ-activated gene (pagL) Salmonella typhimurium, encoding deacylase that removes R-3-hydroxymyristate moiety attached at position 3 certain precursors. was identified...
Modification of bacterial surface structures, such as the lipid A portion lipopolysaccharide (LPS), is used by many pathogenic bacteria to help evade host innate immune response. Helicobacter pylori, a gram-negative bacterium capable chronic colonization human stomach, modifies its removal phosphate groups from 1- and 4′-positions backbone. In this study, we identify enzyme responsible for dephosphorylation 4′-phosphate group in H. Jhp1487 (LpxF). To ascertain role these modifications play...
ABSTRACT Acinetobacter baumannii is an emerging Gram-negative pathogen found in hospitals and intensive care units. In order to persist hospital environments, A. withstands desiccative conditions can rapidly develop multidrug resistance conventional antibiotics. Cationic antimicrobial peptides (CAMPs) have served as therapeutic alternatives because they target the conserved lipid A component of outer membrane lyse bacterial cell. However, many pathogenic bacteria, including , fortify their...
During its transport to the bacterial surface, phosphate groups of lipid A anchor Escherichia coli and Salmonella lipopolysaccharide are modified by membrane enzymes including ArnT, EptA LpxT. ArnT catalyse periplasmic addition positively charged substituents 4-amino-4-deoxy-L-arabinose phosphoethanolamine respectively. These modifications controlled PmrA transcriptional regulator confer resistance cationic antimicrobial peptides, polymyxin. LpxT, however, catalyses phosphorylation at...
Historically, the O1 El Tor and classical biotypes of Vibrio cholerae have been differentiated by their resistance to antimicrobial peptide polymyxin B. However, molecular mechanisms associated with this phenotypic distinction remained a mystery for 50 y. Both Gram-negative Gram-positive bacteria modify cell wall components amine-containing substituents reduce net negative charge bacterial surface, thereby promoting cationic resistance. In present study, we demonstrate that V. lipid A anchor...
Significance Antimicrobial drug resistance is a major threat to public health. Gram-negative bacteria are exceptionally resistant antibiotics because of their outer-membrane barrier. Glycolipids called lipopolysaccharide (LPS) or lipooligosaccharide (LOS) fortify the outer membrane from many antimicrobials and biocides were thought be essential for bacterial survival. The last-resort treatment multidrug-resistant infections colistin, which targets lipid A domain LPS/LOS disrupt membrane, but...
Significance Conjugate vaccines have proven to be an effective and safe strategy for reducing the incidence of disease caused by bacterial pathogens. However, manufacture these is technically demanding, inefficient, expensive, thereby limiting their widespread use. Here, we describe alternative methodology generating glycoconjugate whereby recombinant polysaccharide biosynthesis coordinated with vesicle formation in nonpathogenic Escherichia coli , resulting glycosylated outer membrane...
Significance The outer membrane of Gram-negative bacteria prevents the entry many antibiotics and limits treatment options for infections. This unique is effective due to its asymmetric lipid composition, with glycolipid A [LPS or lipooligosaccharide (LOS)] in leaflet at cell surface glycerophospholipids inner leaflet. Furthering our understanding how asymmetry maintained critical development novel therapeutics target multidrug-resistant bacteria. Here, we used a bacterium without LOS probe...
Polymyxins are antibiotics used in the last line of defense to combat multidrug-resistant infections by Gram-negative bacteria. Polymyxin resistance arises through charge modification bacterial outer membrane with attachment cationic sugar 4-amino-4-deoxy-l-arabinose lipid A, a reaction catalyzed integral lipid-to-lipid glycosyltransferase 4-amino-4-deoxy-L-arabinose transferase (ArnT). Here, we report crystal structures ArnT from Cupriavidus metallidurans, alone and complex carrier...
In Salmonella enterica, PmrD is a connector protein that links the two-component systems PhoP-PhoQ and PmrA-PmrB. While Escherichia coli encodes homolog, it thought to be incapable of connecting PhoPQ PmrAB in this organism due functional divergence from S. enterica protein. However, our laboratory previously observed low concentrations Mg(2+), PhoPQ-activating signal, leads induction PmrAB-dependent lipid A modifications wild-type E. (C. M. Herrera, J. V. Hankins, Trent, Mol Microbiol...